Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

WHAT IS KNOWN AND OBJECTIVE: There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. METHODS: Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. RESULTS AND DISCUSSION: Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. WHAT IS NEW AND CONCLUSION: We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure.

Comparative analysis of the efficacy of omega-3 fatty acids for hypertriglyceridaemia management in Korea.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to compare the ability of statin monotherapy (ST group), omega-3 fatty acid monotherapy (OM_A group) and combination therapy with omega-3 fatty acids and a statin (OM_S group), to reduce triglyceride (TG) levels in patients with hypertriglyceridaemia. METHODS: In this retrospective cohort study, we extracted data from the electronic medical records of patients initially prescribed either a statin or omega-3 fatty acids between January, 2009 and December, 2013. We performed a comparative analysis of the change in cholesterol levels between baseline and an average of 3 months later. RESULTS AND DISCUSSION: Data were extracted for 2071 patients. The average daily eicosapentaenoic acid (EPA) ethyl ester and docosahexaenoic acid (DHA) ethyl ester intake was 1689 mg, and 79-86% of the OM_A and OM_S groups were prescribed two omega-3 fatty acid capsules. At a baseline TG level of between 200 and 500 mg/dL, TG levels were reduced by 16 ± 2·8% in the ST group, 28 ± 2·8% in the OM_A group and 29 ± 2·3% in the OM_S group (P = 0·001 for ST group vs. OM_A and OM_S groups), with no difference between the OM_A and OM_S groups. At a baseline TG level ≥500 mg/dL, there was no difference in TG level reduction between the three groups (54 ± 7·3%, 55·8 ± 3·5% and 51·8 ± 6·8%, respectively, P = 0·851). WHAT IS NEW AND CONCLUSION: Although omega-3 fatty acids are not considered the primary medication for hypertriglyceridaemia, the prescription of omega-3 fatty acids is justifiable if reduction in TG levels is judged to be necessary.

Statin-related aminotransferase elevation according to baseline aminotransferases level in real practice in Korea.

WHAT IS KNOWN AND OBJECTIVE: Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. METHODS: Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. RESULTS AND DISCUSSION: The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. WHAT IS NEW AND CONCLUSION: It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.

Analysis and comparison of statin prescription patterns and outcomes according to clinical department.

WHAT IS KNOWN AND OBJECTIVE: There is a disparity between the Korean treatment guidelines and actual clinical prescription habits. This study was designed to evaluate the department-specific disparities and achievement rates for low-density lipoprotein cholesterol (LDL-C) targets, based on each department's specific statin prescription patterns. METHODS: We retrospectively evaluated data from 31 718 patients who had been prescribed a statin at least once between January 2008 and June 2013 at our institution. Patients were classified into the high-risk (target LDL-C < 100 mg/dL) or moderate-risk (target LDL-C < 130 mg/dL) groups, according to the National Cholesterol Education Programme-Adult Treatment Panel III guidelines. RESULTS AND DISCUSSION: Statins were most commonly prescribed in the cardiology (32·0%) and endocrinology (26·6%) departments. For the high-risk group, 70% of patients in the cardiology, endocrinology and cardiac surgery departments achieved their target LDL-C levels (<100 mg/dL). However, the target achievement rates in most other departments were <70%. For the moderate-risk group, 79·2% of patients achieved their target levels. Departments that prescribed a greater number of high- or intermediate-potency statins were more likely to achieve their target LDL-C levels. The group that achieved their target LDL-C levels (<100 mg/dL) exhibited a significant positive relationship (Spearman's correlation coefficient = 0·8571, P = 0·0065), from low to high potency. WHAT IS NEW AND CONCLUSION: Some departments tend to undertreat when prescribing statins. However, to reach to the target LDL-C levels, physicians must overcome their tendency to undertreat with statins. We believe that the target achievement rate will increase if doctors are more actively aware of a patient's individual status and related risk factors before prescribing statins.

First Report of Powdery Mildew Caused by Podosphaera xanthii on Sechium edule in Korea.

Sechium edule (Jacq.) Sw. (Cucurbitaceae, chayote, mirliton) is native to Mexico and Central America. Several trials have recently been conducted to determine the ability of chayote cultivars to grow under the climatic and soil conditions of South Korea. In April 2013, chayote plants were observed showing typical symptoms of powdery mildew in a glasshouse in Jeju City, Korea. Powdery mildew colonies were circular to irregular, forming white patches on both sides of the leaves. As the disease progressed, entire leaves were covered with white mycelium, followed by leaf withering and premature senescence. The same symptoms were also found on chayote plants in a polyethylene-film-covered greenhouse in Iksan City, Korea, in 2014. Voucher specimens were deposited in the Korea University Herbarium (KUS-F27289, F27422, F28186). Hyphae were flexuous to straight, branched, septate, and 5 to 7 µm wide. Appressoria on the mycelium were nipple-shaped or nearly absent. Conidiophores were straight, 150 to 240 × 10 to 12 µm and produced three to seven immature conidia in chains with a crenate outline. Foot-cells of conidiophores were straight, cylindric, and 52 to 85 µm long. Conidia were hyaline, ellipsoid-ovoid to barrel-shaped, measured 27 to 36 × 16 to 23 µm with a length/width ratio of 1.3 to 2.0, and had distinct fibrosin bodies. Simple to forked germ tubes were produced from the lateral position of conidia. No chasmothecia were found. These structures are typical of the powdery mildew Euoidium anamorph of the genus Podosphaera. Dimensions of foot-cells and conidia were within the ranges provided for P. xanthii (Castagne) U. Braun & Shishkoff, and the length/width ratio of conidia, appressorial characteristics, and conidial germination patterns also conformed to the standard description (2). To confirm the identification, the complete internal transcribed spacer (ITS) region of rDNA of isolate KUS-F27289 was amplified with primers ITS1 and ITS4 and sequenced directly. The resulting 473-bp sequence was deposited in GenBank (Accession No. KM657960). A GenBank BLAST search of the Korean isolate showed 99% similarity with P. xanthii isolates from cucurbitaceous hosts (e.g., AB774155 to AB774158, AB040321, JQ340082, etc.). Pathogenicity was confirmed through inoculation tests by gently pressing a diseased leaf onto young leaves of three asymptomatic, potted chayote plants. Three non-inoculated plants were used as controls. Plants were maintained in a greenhouse at 24 to 34°C. Inoculated leaves started to develop symptoms after 5 days, whereas the control plants remained symptomless. The pathogenicity test was carried out twice with similar results. Powdery mildews of chayote caused by Podosphaera species have been reported in Australia, South Africa, Portugal, India, China, and the United States (1,3,4). To our knowledge, this is the first report of powdery mildew caused by P. xanthii on chayote in Korea. Since chayote production was only recently started on a commercial scale in Korea, powdery mildew infections may pose a serious threat to the safe production of this vegetable. References: (1) P. Baiswar et al. Australas. Plant Dis. Notes 3:160, 2008. (2) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11. CBS, Utrecht, 2012. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab. Online publication, ARS, USDA, Retrieved October 4, 2014. (4) R. Singh et al. Plant Dis. 93:1348, 2009.

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

Peucedanum japonicum Thunb., belonging to the family Apiaceae, is distributed in many Asian countries, including Korea. This plant was recently developed as an edible green and is cultivated under organic farming in Korea. In June 2013, plants showing typical symptoms of powdery mildew were found with approximately 50% disease incidence in polyethylene-film-covered greenhouses in Iksan City, Korea. Symptoms first appeared as circular white colonies, which subsequently showed abundant mycelial growth on the leaves, often covering the whole surface. Infected plants were unmarketable mainly due to signs of white fungal growths and reddish discoloration on the leaves. The same symptoms were found on P. japonicum in poly-tunnels in Iksan City and Jinan County of Korea in 2014. Voucher specimens (n = 3) were deposited in the Korea University Herbarium (KUS). Appressoria were lobed, and solitary or in opposite pairs. Conidiophores were cylindrical, 80 to 145 × 8 to 10 µm, and composed of three to four cells. Foot-cells of conidiophores were straight to substraight, cylindrical, and 25 to 63 µm long. Singly produced conidia were oblong-elliptical to oblong, occasionally ovate, 35 to 50 × 13 to 16 µm with a length/width ratio of 2.3:3.1, with angular/rectangular wrinkling of outer walls, and lacked distinct fibrosin bodies. Germ tubes were produced on the perihilar position of conidia. Primary conidia were apically conical, basally truncate, and generally smaller than the secondary conidia. No chasmothecia were found. These structures are typical of the powdery mildew Pseudoidium anamorph of the genus Erysiphe. The specific measurements and morphological characteristics were consistent with those of E. heraclei DC. (2). To confirm the identification, the complete internal transcribed spacer (ITS) region of rDNA from KUS-F27872 was amplified with primers ITS1/ITS4 and sequenced. The resulting 560-bp sequence was deposited in GenBank (Accession No. KM491178). The obtained ITS sequence shared >99% similarity with those of E. heraclei from apiaceous hosts, e.g., Daucus carota (KC480605), Pimpinella affinis (AB104513), and Petroselinum crispum (KF931139). Pathogenicity was confirmed through inoculation by gently dusting conidia onto leaves of five healthy potted plants. Five non-inoculated plants served as controls. Inoculated plants developed symptoms after 6 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was identical in morphology to those observed in the field. Powdery mildew of P. japonicum caused by E. heraclei has been reported in Japan (4), and numerous reports of E. heraclei on various species of Peucedanum plants have been made in most part of Europe and East Asia (Japan and far eastern Russia) (1,3). However, this is the first report of powdery mildew caused by E. heraclei on P. japonicum in Korea. Occurrence of powdery mildews is a threat to the quality and marketability of this plant, especially in organic farming. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi. Japan Scientific Societies Press, Tokyo, 1986. (2) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (3) D. F. Farr and A. Y. Rossman. Fungal Databases, Syst. Mycol. Microbiol. Lab., online publication. ARS, USDA. Retrieved August 18, 2014. (4) S. Tanda and C. Nakashima. J. Agric. Sci., Tokyo Univ. Agric. 47:54, 2002.

First Report of Leaf Spot Caused by Pseudocercospora pruni-persicicola on Sweet Cherry in Korea.

Sweet cherry, Prunus avium (L.) L., is not much cultivated in Korea, with only 150 ha planted for domestic consumption. In September 2012, a previously unknown leaf spot was observed with nearly 100% incidence on trees (cv. Seneca) planted in a plastic greenhouse in Iksan City of Korea. Interestingly, the same cultivar as well as other cultivars planted outdoors did not show these symptoms. Leaf spots were irregular to subcircular, dark brown with or without a yellow halo, and becoming coalesced to cause leaf blight and premature defoliation. A cercosporoid fungus was consistently associated with disease symptoms. Fungal structures within the lesion developed on both leaf sides but mostly on the upper side. Stromata were well-developed, globular, dark brown, composed of textura angularis-globosa, and 30 to 80 µm in diameter. Conidiophores were densely fasciculate, pale olivaceous to pale brown, subcylindrical, geniculate-sinuous, 8 to 24 × 3 to 4 µm, and aseptate to 2-septate. Conidiogenous loci were inconspicuous, neither thickened nor darkened. Conidia were olivaceous, generally darker than conidiophores, cylindrical to obclavate, almost straight to mildly curved, short obconically truncate at the base, obtuse at the apex, 1- to 10-septate, constricted at the septa, 12 to 86 × 3.5 to 5 µm, guttulate, and had unthickened, not darkened hila. Morphological characteristics of the fungus were consistent with previous descriptions of Pseudocercospora pruni-persicicola (J.M. Yen) J.M. Yen (1,3). A voucher specimen was deposited in the Korea University herbarium (Accession No. KUS-F27264) and a monoconidial isolate was deposited in the Korean Agricultural Culture Collection (Accession No. KACC47019). The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 (4) and sequenced. The resulting 505-bp sequence was deposited in GenBank (Accession No. KF670713). A BLAST search in GenBank revealed that the sequence showed >99% similarity with sequences of many Pseudocercospora species, indicating the close phylogenetic relationship of species in this genus. To conduct a pathogenicity test, a conidial suspension (~1 × 104 conidia/ml) was prepared in sterile water by harvesting conidia from 2-week-old cultures on V8 juice agar, and the suspension was sprayed until runoff onto the leaves of five healthy seedlings. Control plants were sprayed with sterile water. The plants were covered with plastic bags to maintain a relative humidity of 100% for 48 h and then transferred to a greenhouse. Necrotic spots appeared on the inoculated leaves 20 days after inoculation, and were identical to the ones observed in the field. P. pruni-persicicola was re-isolated from symptomatic leaf tissues, fulfilling Koch's postulates. Control plants remained symptomless. The fungus has previously been recorded on Prunus persica (L.) Stokes in Taiwan (2,3). To our knowledge, this is the first report of this fungus on P. avium globally as well as in Korea. The disease poses a new threat to the sweet cherry industry in Korea. References: (1) U. Braun and V. A. Melnik. Cercosporoid Fungi from Russia and Adjacent Countries. Rus. Acad. Sci., St.-Petersburg, 1997. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved August 24, 2013. (3) J. M. Yen. Rev. Mycol. 42:57, 1978. (4) T. J. White et al. PCR Protocols. Academic Press, San Diego, CA, 1990.

First Report of Leaf Spot Caused by a Phoma sp. on Schisandra chinensis in Korea.

Schisandra chinensis (Turcz.) Baill. is a deciduous woody vine native to northern China and the Russian Far East. Its berries have long been used in traditional Asian medicine. In Korea, S. chinensis is one of 10 major medicinal crops and, as of 2011, the production is 6,892 metric tons from 1,749 ha of cultivation area (1). During summer to autumn of 2011 and 2012, leaf spots were observed on S. chinensis (cv. Cheongsun) with disease incidence of 100% in many locations of Jangsu County, Korea. Early symptoms appeared as small, circular, and pale brown spots. Each spot increased in size, became grayish brown and necrotic, and finally developed concentric rings with a definite margin. Some spots coalesced to cover nearly half of the leaves, often becoming torn and giving a shot hole effect. The infected leaf tissue contained blackish pycnidia from which masses of conidia were released in a humid environment. The pycnidia were brown, globose to pyriform, ostiolate, and 45 to 160 µm in diameter. Conidia were hyaline, smooth, oval to ellipsoidal, aseptate or medianly 1-septate, very occasionally 2-septate, slightly constricted at the septa, 4 to 11 × 2.5 to 5 µm, and contained small oil drops. These morphological characteristics were consistent with the generic concept of Phoma (2). Three monoconidial isolates were successfully cultured by diluting conidia mass in sterile water and streaking conidia suspension on potato dextrose agar (PDA). A representative isolate was deposited in the Korean Agricultural Culture Collection (Accession No. KACC47113) and used for pathogenicity test and molecular analysis. Inoculum for a pathogenicity test was prepared by harvesting conidia from 30-day-old cultures (12-h diurnal cycle, 25°C) and a conidial suspension in water (1.1 × 107 conidia/ml) was sprayed onto leaves of three healthy seedlings (cv. Cheongsun). Three seedlings serving as controls were sprayed until runoff with sterile distilled water. The plants were separately covered with plastic bags for 48 h in a glasshouse. After 10 days, typical leaf spot symptoms developed on the leaves inoculated with the fungus. Phoma sp. was re-isolated from those lesions, confirming Koch's postulates. No symptoms were observed on controls. The pathogenicity test was conducted twice. Fungal DNA was extracted, and the complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 and sequenced directly. The resulting 520-bp sequence was deposited in GenBank (Accession No. KC928322). The sequence showed over 99% similarity with many Phoma species from various substrates, but no exact matches. Phoma leaf spot of S. chinensis was once recorded in Korea without pathogenicity test and culture deposition (3). Phoma glomerata was recorded as a causal fungus of leaf spot disease on S. chinensis in China (4). The Korean isolates differ from P. glomerata in having larger conidia and are separated from it in ITS sequence data. Therefore, we tentatively place the Korean isolates as unidentified Phoma sp. To our knowledge, this is the first confirmed report of leaf spot disease caused by a Phoma sp. in Korea. References: (1) Anonymous. Statistics of Cultivation and Production of Industrial Crops in 2011. Korean Ministry for Food, Agriculture, Forestry and Fisheries. 2012. (2) M. M. Aveskamp et al. Mycologia 101:363, 2009. (3) E. J. Lee et al. Compendium of Medicinal Plant Diseases with Color Plates. Nat. Inst. Agric. Sci., Suwon, Korea. 1991. (4) X. Wang et al. Plant Dis. 96:289, 2012.

First Report of Quinoa Downy Mildew Caused by Peronospora variabilis in Republic of Korea.

Quinoa (Chenopodium quinoa Willd.) has become increasingly popular due to its high nutritional value and adaptability to harsh environments. Several field trials have recently been conducted to determine the ability of quinoa cultivars to grow under climate and soil conditions of Republic of Korea. During July 2013, which is the rainy season, plants showing typical symptoms of downy mildew were first observed in an experimental plot in Iksan City, Korea. Infection resulted in small to large, irregular chlorotic areas on the upper leaf surface with a gray mildew developing on the abaxial surface, and often leading to early defoliation. The same symptoms of downy mildew were also found in Pyeongchang County and Imsil County, Korea. A sample from Iksan City was deposited in the Korea University Herbarium (Accession No. KUS-F27388) and used for microscopy and molecular studies. Microscopic examination revealed colorless conidiophores emerging from stomata, straight to slightly curved, 350 to 550 × 10 to 18 µm, and sub-dichotomously branched in 5 to 7 orders. Ultimate branchlets were mostly in pairs, flexuous to curved, 10 to 30 µm long, and had obtuse tips. Conidia were pale brown to olivaceous, broadly ellipsoidal to ellipsoidal, and 25 to 32 × 22 to 25 µm with a length/width ratio of 1.20 to 1.35. These characteristics fit well with Peronospora variabilis, which was previously recorded to be parasitic to C. quinoa and C. album, although P. farinosa f. sp. chenopodii has often been considered a causal agent of downy mildew on quinoa (1). To confirm this morphological identification, amplification and sequencing of the internal transcribed spacer (ITS) region of the rDNA of the Korean specimen were performed using procedures outlined by Choi et al. (1) with oomycete-specific primers DC6 and LR0. The resulting 796-bp sequence was deposited in GenBank (Accession No. KF887493). A comparison with the ITS sequences available in GenBank revealed that it is identical to P. variabilis found on C. album (EF614959, EF614961), and shows only one base pair substitution with another isolates from C. quinoa (EU113305, EU113306). Therefore, the pathogen found in Korea was confirmed to be P. variabilis. Downy mildew is the most damaging disease of quinoa in Argentina, Bolivia, Colombia, Ecuador, and Peru (1). Increasing reports of this disease from India, Canada, the United States, Portugal, and Denmark (2,3,4) have revealed its worldwide occurrence and spread. To our knowledge, this is the first report of a downy mildew on quinoa in Korea (3). It suggests that quinoa downy mildew poses a new and serious threat to production of this crop in Korea. References: (1) Y. J. Choi et al. Mycopathologia 169:403, 2010. (2) S. Danielson et al. Seed Sci. Technol. 32:91, 2004. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved November 5, 2013. (4) A. L. Testen et al. Plant Dis. 96:146, 2012.

First Report of Powdery Mildew Caused by Golovinomyces biocellatus on Agastache rugosa in Korea.

Agastache rugosa (Fisch. & C.A. Mey.) Kuntze, known as Korean mint, is an aromatic plant in the Lamiaceae. It is widely distributed in East Asian countries and is used as a Chinese traditional medicine. In Korea, fresh leaves are commonly added to fish soups and stews (3). In November 2008, several dozen Korean mints plants growing outdoors in Gimhae City, Korea, were found to be severely infected with a powdery mildew. The same symptoms had been observed in Korean mint plots in Busan and Miryang cities from 2008 to 2013. Symptoms first appeared as thin white colonies, which subsequently developed into abundant hyphal growth on stems and both sides of the leaves. Severe disease pressure caused withering and senescence of the leaves. Voucher specimens (n = 5) were deposited in the Korea University Herbarium (KUS). Appressoria on the mycelium were nipple-shaped or nearly absent. Conidiophores were 105 to 188 × 10 to 13 µm and produced 2 to 4 immature conidia in chains with a sinuate outline, followed by 2 to 3 cells. Foot-cells of the conidiophores were straight, cylindrical, slightly constricted at the base, and 37 to 58 µm long. Conidia were hyaline, ellipsoid to barrel-shaped, measured 25 to 40 × 15 to 23 µm (length/width ratio = 1.4 to 2.1), lacked distinct fibrosin bodies, and showed reticulate wrinkling of the outer walls. Primary conidia were obconically rounded at the apex and subtruncate at the base. Germ tubes were produced at the perihilar position of conidia. No chasmothecia were observed. The structures described above were typical of the Oidium subgenus Reticuloidium anamorph of the genus Golovinomyces. The measurements and morphological characteristics were compatible with those of G. biocellatus (Ehrenb.) V.P. Heluta (1). To confirm the identification, molecular analysis of the sequence of the internal transcribed spacer (ITS) region of ribosomal DNA (rDNA) of isolate KUS-F27200 was conducted. The complete ITS rDNA sequence was amplified using primers ITS5 and P3 (4). The resulting 514-bp sequence was deposited in GenBank (Accession No. KJ585415). A GenBank BLAST search of the Korean isolate sequence showed >99% similarity with the ITS sequence of many G. biocellatus isolates on plants in the Lamiaceae (e.g., Accession Nos. AB307669, AB769437, and JQ340358). Pathogenicity was confirmed by gently pressing diseased leaf onto leaves of five healthy, potted Korean mint plants. Five non-inoculated plants served as a control treatment. Inoculated plants developed symptoms after 7 days, whereas the control plants remained symptomless. The fungus present on inoculated plants was identical morphologically to that observed on the original diseased plants. The pathogenicity test was repeated with identical results. A powdery mildew on A. rugosa caused by G. biocellatus was reported from Romania (2). To our knowledge, this is the first report of powdery mildew caused by G. biocellatus on A. rugosa in Korea. The plant is mostly grown using organic farming methods with limited chemical control options. Therefore, alternative control measures should be considered. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11. CBS, Utrecht, 2012. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., online publication, USDA ARS, retrieved 17 February 2014. (3) T. H. Kim et al. J. Sci. Food Agric. 81:569, 2001. (4) S. Takamatsu et al. Mycol. Res. 113:117, 2009.

First Report of Black Stem Caused by Botryosporium longibrachiatum on Statice in Korea.

Perennial statice is widely cultivated worldwide. In Korea, hybrid statice (Limonium latifolium × bellidifolium) is grown as a commercial cut flower crop in polyethylene-film-covered greenhouses. In April 2013, hundreds of hybrid statice plants of the cvs. Yellow Cream and Pinky Cream were found symptomatic of a previously unknown disease, with 10 to 15% incidence in 10 greenhouses of 1,600 m2 surveyed in Gochang County, Korea. Affected stems turned dark brown and were usually covered with a fungus resembling the hoar-frost fungus, Botryosporium longibrachiatum (3), especially in a cool and humid environment. Symptoms consisted of stem blackening, as is typical for burley tobacco (1) and sweet basil (2). According to the farmer of the hybrid statice, stems blackened in the winter and spring of January to April when the tunnels were mostly closed, thus reaching 100% relative humidity (RH) every night due to poor ventilation. The fungus had an elongate main axis with lateral fertile branches in acropetal succession. Conidiophores were simple, erect, macronematous, 32 to 79 µm in length, with a terminal cluster of three to five ampullae. Conidiogneous cells were polyblastic. Conidia were ellipsoidal, elliptical-fusiform, hyaline, 7.6 to 9.5 × 3.0 to 4.2 µm. Colonies on potato dextrose agar (PDA) were floccose, non-pigmented, and chalk-white in color. Morphological and cultural characteristics of the fungus were consistent with previous reports of B. longibrachiatum (Oudem.) Maire (2,3). A voucher specimen was deposited in the Korea University Herbarium (KUS). Isolate KUS-F27305 was submitted to the Korean Agricultural Culture Collection (Accession No. KACC47263). Fungal DNA was extracted from isolate KACC47263 with DNeasy Plant Mini Kits. The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 and sequenced. The resulting sequence of 604 bp was deposited in GenBank (Accession No. KF372591). A BLAST search in GenBank exhibited ≥99% nucleotide identity with the ITS sequence of B. longibrachiatum (JX666334) from sweet basil in Korea. To confirm pathogenicity, colonized mycelial agar blocks from isolate KACC47263 were transferred individually onto stem apices and leaves of five statice plants of the cv. Yellow Cream. Five control plants were treated similarly with non-colonized agar blocks. The plants were incubated in a humid chamber at 22 ± 2°C with a 12-h photoperiod for 48 h, and then maintained in 100% RH. After 3 to 4 days, necrotic lesions identical to those observed in the original greenhouses, started to develop on the stem and leaves of inoculated plants, leading to blackened stems covered with the hoar-frost fungus after 14 days. B. longibrachiatum was re-isolated from the lesions of inoculated plants, fulfilling Koch's postulates. No symptoms were observed on control plants. The pathogenicity test was repeated with the cv. Pinky Cream with identical results. To our knowledge, this is the first report of B. longibrachiatum infecting perennial statice globally as well as in Korea. We propose the name black stem of statice for this disease, analogous to the disease on basil (2). References: (1) T. R. Anderson and T. W. Welacky. Plant Dis. 67:1158, 1983. (2) J. H. Park et al. Plant Dis. 97:425, 2013. (3) C. V. Subramanian. Hyphomycetes. Indian Council of Agricultural Research, New Delhi, India, 1971.

First Report of Anthracnose Caused by Colletotrichum lupini on Yellow Lupin in Korea.

Yellow lupin (Lupinus luteus L.) is native to the Mediterranean region of southern Europe. In Korea, yellow lupins are cultivated for ornamental purposes. In May 2013, hundreds of yellow lupins that were grown in pots for 7 weeks in polyethylene-film-covered greenhouses were observed severely damaged by a previously unknown disease with about 30% disease incidence in a flower farm in Yongin City, Korea. Voucher specimens were deposited in the Korea University Herbarium (KUS). Early symptoms on petioles and stems appeared as small, slightly sunken, water-soaked, and circular spots. Lesions increased in size (4 to 12 µm in diameter), became more depressed, with a darkened central portion. As the disease progressed, affected areas sometimes girdled the stem and killed the shoot. Leaves were partly blighted, but less damaged. The darkened areas contained blackish acervuli from which masses of pale salmon-colored conidia were released in moist weather. Acervuli were circular to ellipsoid, 80 to 400 µm in diameter. Acervular setae were not observed. Conidia (n = 30) were long obclavate to oblong-elliptical, aguttulate, hyaline, and 10 to 18 × 3.6 to 5.2 µm with a length/width ratio of 2.6 to 3.6. Appressoria were single or occasionally in small dense clusters, medium brown, elliptical to round in outline with a smooth to lobate margin, and 8 to 14 × 6 to 9 µm. These characters were consistent with the description of Colletotrichum lupini (Bondar) Damm, P.F. Cannon & Crous (1,3). An isolate was deposited in the Korean Agricultural Culture Collection (Accession No. KACC47254). Fungal DNA was extracted with DNeasy Plant Mini DNA Extraction Kits (Qiagen Inc., Valencia, CA). The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 and sequenced. The resulting 545-bp sequence was deposited in GenBank (Accession No. KJ447119). The sequence showed 100% identity with sequences of C. lupini (e.g., GenBank AJ301968, JN943480, JQ948162, and KF207599). To confirm pathogenicity, inoculum was prepared by harvesting conidia with sterile distilled water from 3-week-old cultures on potato dextrose agar. A conidial suspension (2 × 105 conidia/ml) was sprayed until runoff onto the aerial parts of five healthy plants. Control plants were sprayed with sterile water. The plants were covered with plastic bags to maintain a relative humidity of 100% for 48 h and then transferred to a greenhouse. Typical symptoms of necrotic spots appeared on the inoculated leaves 6 days after inoculation, and were identical to the ones observed in the field. C. lupini was re-isolated from symptomatic leaf tissues. No symptoms were observed on control plants. The pathogenicity test was repeated twice. Anthracnose associated with C. lupini on lupins has been known from Europe (Germany, Ukraine, Austria, and Netherlands), North America (Canada and the United States), South America (Bolivia and Brazil), and Oceania (Australia and New Zealand) (2,4). To our knowledge, this is the first report of C. lupini on yellow lupins in Asia as well as in Korea. The presence of C. lupini on lupins in Asia can be considered as a potentially new and serious threat to this ornamental plant. References: (1) U. Damm et al. Stud. Mycol. 73:37, 2012. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved February 17, 2014. (3) H. I. Nirenberg et al. Mycologia 94:307, 2002. (4) E. Rosskopf et al. Plant Dis. 98:161, 2014.

First Report of Powdery Mildew Caused by Golovinomyces artemisiae on Artemisia annua in Korea.

Artemisia annua L., known as sweet wormwood or sweet annie, is native to temperate Asia, but is naturalized throughout the world. It produces artemisinin, a potent antimalarial drug that is also effective in treating other parasitic diseases (4). In August 2013, hundreds of plants showing typical symptoms of powdery mildew were found in Seoul (37°36'29.4″ N 127°02'38.3″ E), Korea. Powdery mildew colonies first appeared as thin white patches, which progressed to abundant hyphal growth on both sides of the leaves, stems, and inflorescence. As symptoms continued to develop, the leaves became distorted and turned purplish-gray. Severe infections caused leaf withering and premature senescence. The same symptoms were found on sweet wormwoods in Nonsan (36°09'55.3″ N 127°01'07.1″ E) and Chuncheon (37°52'27.4″ N 127°43'10.0″ E), Korea. Voucher specimens were deposited in the Korea University Herbarium (KUS). Appressoria on the mycelium were nipple-shaped or occasionally lobed. Conidiophores were cylindrical, measured 120 to 230 × 10 to 12.5 µm, and produced 2 to 4 immature conidia in chains with a sinuate outline, followed by 2 to 3 cells. Foot-cells of conidiophores were straight, cylindrical, and 54 to 100 µm long. Conidia were hyaline, ellipsoid to barrel-shaped, measured 30 to 40 × 15 to 20 µm (length/width ratio of 1.5 to 2.1), lacked distinct fibrosin bodies, and showed reticulate wrinkling of the outer walls. Germ tubes were produced on the perihilar position of conidia. Primary conidia were apically rounded, basally subtruncate, and generally smaller than the secondary conidia. No chasmothecia were observed. The structures described above were typical of the powdery mildew Euoidium anamorph of the genus Golovinomyces, and the fungus measurements were similar to those of G. artemisiae (Grev.) V.P. Heluta (3). The complete internal transcribed spacer (ITS) region of rDNA from KUS-F27763 was amplified with primers ITS1/ITS4 and sequenced. The resulting sequence of 624 bp was deposited in GenBank (Accession No. KJ136112). The obtained ITS sequence shared >99% similarity with G. artemisiae on A. princeps and A. montana from Japan (AB077659 and AB077649) and A. argyi from China (KF056818). Pathogenicity was confirmed through inoculation by gently dusting conidia onto leaves of five healthy potted plants. Five non-inoculated plants served as controls. Inoculated plants developed symptoms after 5 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants. Powdery mildews of A. annua caused by G. artemisiae have been reported in Japan, China, the Russian Far East, and Romania (1,2). To our knowledge, this is the first report of powdery mildew caused by G. artemisiae on A. annua in Korea. Since sweet wormwood production was only recently started on a commercial scale in Korea, powdery mildew infections pose a serious threat to the production of this plant, especially in organic farming where chemical control options are limited. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi. Japan Scientific Societies Press, Tokyo, 1986. (2) U. Braun. The Powdery Mildews (Erysiphales) of Europe. G. Fischer Verlag, Jena, 1995. (3) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (4) P. J. Weathers et al. Phytochem. Rev. 10:173, 2011.

First Report of Powdery Mildew Caused by Erysiphe buhrii on Gypsophila paniculata in Korea.

Gypsophila paniculata L. (baby's breath, family Caryophyllaceae), native to Central and Eastern Europe, is commonly cultivated as a commercial cut flower crop in greenhouses in Korea. Since 2011, baby's breath cv. Cassiopeia has been observed affected by a powdery mildew with nearly 100% disease incidence at the stage of harvesting in Iksan City. Powdery mildew colonies first appeared as thin white patches on stems and both sides of the leaves. As disease progressed, plants were covered with dense masses of spores, followed by senescence and reduction of quality of cut flowers. A voucher specimen was deposited in the Korea University Herbarium (Accession KUS-F27313). Appressoria were well-developed, multilobed or moderately lobed, and single or opposite in pairs. Conidiophores were straight, 95 to 150 × 7 to 10 µm, and composed of 3 to 4 cells. Foot-cells were cylindric or slightly sinuous at the base and 37 to 53 µm long. Singly produced conidia were cylindrical to oblong-elliptical, 35 to 56 × 12.5 to 18 µm with a length/width ratio of 2.1 to 3.6, devoid of fibrosin bodies, and with angular/rectangular wrinkling of outer walls. Germ tubes were in the perihilar position on conidia, and ended with lobed appressoria. No chasmothecia were found. These structures are typical of the Pseudoidium anamorph of the genus Erysiphe. Specific measurements and host range were consistent with those of E. buhrii U. Braun (2). To confirm identification, the complete internal transcribed spacer (ITS) region of rDNA of isolate KUS-F27313 was amplified with primers ITS1/ITS4, and sequenced directly. The resulting 725-bp sequence was deposited in GenBank (KJ530705). A GenBank BLAST search of the Korean isolate showed 99% similarity with E. buhrii on Acanthophyllum sp. (Caryophyllaceae) from Iran (AB128924). Pathogenicity was confirmed through inoculation by gently dusting conidia onto leaves of five healthy, potted baby's breath cv. Cassiopeia. Five non-inoculated plants served as controls. Inoculated plants were isolated from non-inoculated plants in separate rooms in a greenhouse at 25 ± 2°C. Inoculated plants developed signs and symptoms after 7 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants. Pathogenicity test was repeated twice. The powdery mildew disease caused by E. buhrii on baby's breath has been recorded in the former Soviet Union (Armenia, Kazakhstan, Ukraine), Romania, Turkey, Iran, Mongolia, and Argentina (1,3). Also, a fungus occurring on baby's breath was recorded as Oidium sp. from Japan (4). To our knowledge, this is the first report of powdery mildew caused by E. buhrii on baby's breath in Korea. Powdery mildew infections pose a serious threat to production of this cut flower crop. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi. Japan Scientific Societies Press, Tokyo, 1986. (2) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11. CBS, Utrecht, 2012. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved February 18, 2014. (4) M. Satou et al. Ann. Phytopathol. Soc. Jpn. 62:541, 1996.

First Confirmed Report of Anthracnose Fruit Rot Caused by Colletotrichum gloeosporioides on Common Fig in Korea.

Common fig (Ficus carica L.) was introduced into Korea in the 1890s from Japan and planted in residential gardens for home consumption. Commercial cultivation of the tree did not begin until the 1990s (2). In early August 2012, several dozen unripened fig fruits, cv. Banane, were found damaged by fruit rot in an experimental plot of Jeollabuk-do Agricultural Research and Extension Services, Iksan City, South Korea (GPS coordinates 35°56'38.44″ N, 126°59'37.14″ E). Though infections recurred until late September, infection rates were as low as 1 to 5%. Early symptoms appeared as small, slightly sunken, water-soaked, and circular spots. Lesions increased in size, became more depressed, with a darkened central portion. The darkened areas contained blackish acervuli from which masses of salmon-colored conidia were released in moist weather. A semisoft decay resulted, sometimes causing premature fruit drop. No symptoms were found on leaves. Acervuli were circular to ellipsoid, 50 to 400 µm in diameter. Acervular setae were 2- to 3-septate, dark brown at the base, paler toward the apices, acicular, and up to 120 µm long. Conidia (n = 30) were long obclavate to oblong-elliptical, sometimes fusiform-elliptical, guttulate, hyaline, and 16 to 21 × 4 to 6 µm. These characters were consistent with the description of Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. (4). From an isolate (KACC46943, deposited in the Korean Agricultural Culture Collection), fungal DNA was extracted, and the complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1(5'-TCCGTAGGTGAACCTGCGG-3')/ITS4(5'-TCCTCCGCTTATTGATATGC-3') and sequenced. The resulting 606-bp sequence was deposited in GenBank (KC430919). The sequence showed 100% identity with sequences of C. gloeosporioides (e.g., JX669446, JQ936316, JQ753973). To confirm pathogenicity, inoculum was prepared by harvesting conidia from 3-week-old cultures on potato dextrose agar. A conidial suspension (3 × 105 conidia/ml) was sprayed onto 10 fruits wounded with a fine needle. Ten fruits sprayed with sterile water served as controls. Fruits were placed in moist chambers for 24 h and then kept in plastic containers (25°C and 60 to 80% RH). After 5 days, fruit rot symptoms, identical to those observed in the field, developed on the inoculated fruits, but never on controls. C. gloeosporioides was reisolated from the lesions of inoculated fruits. Anthracnose associated with C. gloeosporioides on common figs has been known from North America, Central America, South America, Australia, New Zealand, South Africa, and Turkey (1). In Korea, anthracnose fruit rot of common figs was recorded in 1928 under the name C. caricae F. Stevens & J.G. Hall, but without fulfillment of Koch's postulates (3). Subsequent to that time, there has been no published finding of the disease in Korea. C. caricae is regarded as synonymous with C. gloeosporioides (4). To our knowledge, this is the first confirmed report of anthracnose fruit rot of common figs caused by C. gloeosporioides in Korea. Anthracnose fruit rot of common figs may cause losses not only for fruit production but also for marketing. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved January 24, 2013. (2) K. C. Ma et al. Res. Plant Dis. 14:107, 2008. (3) K. Nakata and S. Takimoto. Bull. Agric. Exp. Stat. Korea 15:1, 1928. (4) B. S. Weir et al. 2012. Stud. Mycol. 73:115, 2012.

Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T.

BACKGROUND: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T(2) lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. OBJECTIVE: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. METHODS: Seventeen patients with SPMS (Expanded Disability Status Scale=4.0-7.0; length of MS diagnosis=19.4 ± 7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. RESULTS: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p=0.001). CONCLUSION: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

First Report of Bark Dieback on Blueberry Caused by Botryosphaeria dothidea in Korea.

This study was conducted to identify the causal organism of bark dieback disease of highbush blueberry (Vaccinium corymbosum L.) observed in Korea. Blueberry, a woody plant that is native to North America, belongs to the family Ericaceae and genus Vaccinium. Of the 400 species of blueberry in the world, most are distributed in the tropics of Malaysia and Southeast Asia. Highbush blueberry is abundantly grown in Canada and the United States and has become a popular commercial crop in Korea for products such as jam, wine, and sauce. Bark dieback disease of blueberry was found in Sunchang (<5% incidence), Jeollabuk-do, Korea in July 2009. Typical symptoms of the disease were blight and dieback on the stems with lesions extending along entire branches. Morphological examination revealed that the perithecia were of the globose type with a nipple, 155 to 490 (374.6) µm, and brown on the dead bark. Asci were bitunicate and clavate or cylindrical with dimensions of 63 to 125 × 16 to 20 µm and containing eight ascospores. Ascospores were of the long ovoid type with dimensions of 13.2 to 23.7 (17.98) × 25.4 to 41.1 (33.21) µm. From extracted genomic DNA, the internal transcribed spacer (ITS)-5.8S ribosomal DNA region was amplified with universal primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3'). A BLAST search of GenBank with the ITS sequence revealed that the Sunchang isolate (GenBank Accession No. HQ384217) had 99 to 100% sequence identity with the following Botryosphaeria dothidea accessions: FJ517657, AJ938005, FJ478129, FJ171723, and AJ938004. Phylogenetic analysis with the Sunchang isolate, B. dothidea strains, and related species revealed that the B. dothidea isolate and strains comprised a monophyletic group distinguished from other Botryosphaeria spp. including B. ribis, B. parva, B. protearum, B. lutea, B. australis, B. rhodina, B. obtuse, and B. stevensii (2). On the basis of morphological and molecular results, the isolate was identified as B. dothidea (Moug.) Ces. & De Not. A culture of B. dothidea isolate was grown on potato dextrose agar (PDA) for 10 days. A 5-mm plug was inoculated into stem wounds created with a No. 2 cork borer in 20 2-year-old disease-free blueberry plants grown in a greenhouse. Six plants inoculated with only PDA plugs served as noninoculated controls. The wounds were covered with Parafilm. After 3 months, the Parafilm was removed and black lesions were observed at the fungal inoculation sites, while no lesion was observed on the control plants. To complete Koch's postulates, the fungus was reisolated from the lesions and confirmed to be B. Dothidea (1). There is an urgent need to determine the spread of this disease in Korea, estimate the losses, and develop methods for reducing damage through biological and eco-friendly cultural control methods. References: (1) D. Jurc et al. Plant Pathol. 55:299, 2006. (2) B. Slippers et al. Mycologia 96:83, 2004.

Individual and combined effects of waterlogging and alkalinity on yield of wheat (Triticum aestivum L.) imposed at three critical stages.

Response of wheat genotype HD 2329 to individual and combined effects of alkalinity and waterlogging (WL) at tillering, panicle emergence and anthesis stage was studied. Both stresses increased Na accumulation and reduced K uptake which leads to higher Na(+)/K(+) ratio in the leaves. Yield was decreased under all the stress treatments and highly correlated with Na(+)/K(+) ratio at all the three growth stages (r = -0.83, -0.82 and -0.73, respectively) with maximum reduction under pH 9.4 + WL. Increase in pH from 7.2 to 9.1 and 9.4 delayed complete panicle emergence (4 and 8 days) and flowering (1 and 2 days) at both, tillering and panicle emergence stages. Dual stress further increased days, required for complete panicle emergence and flowering. These results suggested that high Na(+)/K(+) ratio of plant tissue may be the critical factor for growth and development of wheat under WL, alkalinity and dual stress. Due to this delay in flowering and panicle emergence, times required for maturity of grains shorten, resulted in lower grain yield.

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic-pituitary axis hyperactivity caused by prenatal alcohol exposure.

Exposure to alcohol during embryonic development leads to changes in the hypothalamic-pituitary-adrenal (HPA) axis such that adult offspring release more adrenocorticotrophic hormone (ACTH) than controls when exposed to stress. In the present work, we tested the hypothesis that changes in the activity of the catecholaminergic system modulate, at least in part, this upregulation of the HPA axis. Pregnant Sprague-Dawley rats were exposed to alcohol 6 h daily during gestation days 7-18 using the vapor chamber model, which generated mean blood alcohol levels of 188.6+/-10 mg/dl. All experiments were performed on 2 to 3-month-old offspring. We first measured the ACTH response to i.c.v. injection of adrenergic receptor agonists. In rats exposed to footshocks, we then investigated the activity of corticotrophin-releasing factor (CRF) as well as indexes of catecholamine ir, namely tyrosine hydroxylase (TH) immunopositive neurons in the paraventricular nucleus (PVN), TH immunopositive neurons in the locus coeruleus, and phenylethanolamine N-methyltransferase (PNMT) immunopositive neurons in the brain stem. While adult females exposed to alcohol during fetal development (FAE) displayed the expected enhanced ACTH response to stress, there were no significant differences in response to adrenergic receptor agonists or in shock-induced CRF/TH ir and neuronal activity, as determined by c-fos colocalization. In contrast, FAE female offspring exposed to footshocks showed a significant increase in the activity of adrenergic neurons in the C1 region of the brain stem, a population of cells that project to the PVN. Collectively, these results suggest that while FAE-induced hyperactivity of the HPA axis is not accompanied by significant changes in PVN CRF or TH-ir neurons, it is characterized by an upregulation of C1 adrenergic neurons of the brain stem. This novel finding should lead to the functional characterization of this brain region in the FAE model.