Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22

Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects.The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22

Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects.The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

7,8,4′-Trihydroxyisoflavone, a Metabolized Product of Daidzein, Attenuates 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4′-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4′-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4′-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4′-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4′-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3β) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4′-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4′-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/GSK-3β pathways.

A Comparison of Passive Release Technique and Minimal Occlusive Volume Technique for Endotracheal Tube Cuff Inflation

PURPOSE: Inflation of an endotracheal tube cuff with adequate pressure is an important procedure. Passive release technique (PRT) is a useful and convenient method for inflating the cuff. To date, no study comparing this method with minimal occlusive volume technique (MOVT), one of the most commonly used methods for inflating the cuff, has been reported. We conducted this study for comparison of effectiveness, difficulty, and preference between the two methods. METHODS: We conducted a prospective, crossover, randomized study in which participants used each technique, one at a time. Participants inflated the cuff of an endotracheal tube inserted into a manikin after receiving brief education on use of the two methods. After inflating the cuff using each method, pressure and volume of the inflated cuff were measured using a portable manometer and syringes, respectively. Then, difficulty of each method was investigated using the visual analogue scale (VAS) and preference for each method was investigated. RESULTS: A total of 47 participants were enrolled in the study. The mean pressure between the two methods was not statistically different (p=0.27). However, adequate pressure was achieved in 37 (78.7%) and 16 (34.0%) of participants in PRT and MOVT, respectively (p<0.01). The mean volume was 6.0+/-0.4 ml in PRT and 5.7+/-0.6 ml in MOVT (p<0.01). The VAS score for diffculty was 17.7+/-15.8 in PRT and 76.0+/-15.8 in MOVT (p<0.01). Preference for PRT was 46(97.9%) and that for MOVT was 1 (2.1%). CONCLUSION: PRT is an easier, more preferred, and more effective method for cuff inflation than MOVT.

Cultural Characteristics and Log-Mediated Cultivation of the Medicinal Mushroom, Phellinus linteus

The optimal conditions for mycelial growth of Phellinus linteus ATCC 26710 were determined to be a log length of 20 cm, temperature of 30degrees C and pH of 6.0. Mycelial growth was excellent on the mushroom complete medium, and was optimal when sucrose, mannose and glucose were supplied as carbon sources. Potassium nitrate and sodium nitrate as nitrogen sources supported good mycelial growth. To evaluate P. linteus mycelial colonization on logs, sterilized short log inoculation, drilling inoculation and log-end sandwich inoculation techniques were used. Only sterilized short log inoculation produced good mycelial colonization. Initial mycelial growth and full mycelial colonization were best on 20 cm logs having 42% moisture content. The initial mycelial growth of P. linteus was accelerated over 12 hr of sterilization. Basidiocarp formation was optimal using a burying method of logs after 5~6 months, and fruiting body formation was superior in cultivation house conditions of 31~35degrees C and in excess of 96% relative humidity.

Vegetative Growth of Four Strains of Hericium erinaceus Collected from Different Habitats

Vegetative growth of four different strains of Hericium erinaceus was observed. The temperature suitable for optimal mycelial growth was determined to be 25degrees C, with growth observed in the extend temperature range of 20~30degrees C. The different strains of this mushroom showed distinct pH requirements for their optimum vegetative growth, with the most favorable growth observed at pH 6. Considering vegetative mycelial growth, PDA, YM, Hennerberg, Hamada, and Glucose peptone were the most favorable media, and Czapek Dox, Hoppkins, Glucose tryptone, and Lilly were the most unfavorable media for these mushroom strains. With the exception of lactose, most of the carbon sources assayed demonstrated favorable vegetative growth of H. erinaceus. For mycelial growth, the most suitable nitrogen source was alanine and the most unsuitable was histidine. Oak sawdust medium supplemented with 10~20% rice bran was the best for mycelial growth of the mushroom.

Degradation of Three Aromatic Dyes by White Rot Fungi and the Production of Ligninolytic Enzymes

This study was conducted to evaluate the degradation of aromatic dyes and the production of ligninolytic enzymes by 10 white rot fungi. The results of this study revealed that Pycnoporus cinnabarinus, Pleurotus pulmonarius, Ganoderma lucidum, Trametes suaveolens, Stereum ostrea and Fomes fomentarius have the ability to efficiently degrade congo red on solid media. However, malachite green inhibited the mycelial growth of these organisms. Therefore, they did not effectively decolorize malachite green on solid media. However, P. cinnabarinus and P. pulmonarius were able to effectively decolorize malachite green on solid media. T. suaveolens and F. rosea decolorized methylene blue more effectively than any of the other fungi evaluated in this study. In liquid culture, G. lucidum, P. cinnabarinus, Naematoloma fasciculare and Pycnoporus coccineus were found to have a greater ability to decolorize congo red. In addition, P. cinnabarinus, G. lucidum and T. suaveolens decolorized methylene blue in liquid media more effectively than any of the other organisms evaluated in this study. Only F. fomentarius was able to decolorize malachite green in liquid media, and its ability to do so was limited. To investigate the production of ligninolytic enzymes in media containing aromatic compounds, fungi were cultured in naphthalene supplemented liquid media. P. coccineus, Coriolus versicolor and P. cinnabarinus were found to produce a large amount of laccase when grown in medium that contained napthalene.

Suitable Conditions for Mycelial Growth of Phellinus spp

The fungus Phellinus is a mushroom that is widely used medicinally. The optimal conditions for mycelial growth of 13 strains of the fungus were investigated. Mycelial growth was optimal at 25degrees C and was uniformly minimal at 15degrees C and 35degrees C. Growth was optimal at pH 6~7. The mycelial phenotype was best promoted by growth using Potato Dextrose agar, Hamada, Glucose peptone, and Yeast-Malt media, whereas Czapek Dox, Hennerberg, and Lilly media were the most unfavorable for the mycelial growth of Phellinus spp. Glucose, sucrose, fructose, and dextrin were the most suitable carbon sources for mycelial growth, while lactose, maltose, and galactose were unsuitable. Among tested nitrogen sources, ammonium phosphate, potassium nitrate, and arginine best promoted mycelial growth, while alanine, urea, and histidine least promoted mycelial growth.

First Report of Heterodermia squamulosa (Lichenized Ascomycota, Physciaceae) in South Korea

Heterodermia squamulosa (Degel.) W.L. Culb. was found in the mountain of Gariwang, Gangwon province, in 2008. It is characterized by numerous squamules along the margin, decorticate and white lower surface, rhizines along the margin, black and densely squarrosely branched, usually forming a dense mat under the thallus. Apothecia margins densely squamulose, ascospores 12~15 x 25~30 microm. Atranorin and zeorin contained in thallus. This is the first record of this species in South Korea.

Cladonia peziziformis (Lichenized Ascomycota, Cladoniaceae) New to Korea

Cladonia peziziformis (With.) J.R. Laundon was collected from Baega mountain, Jeonnam Province, Korea in 2008. It is characterized by short and slender podetia with verruculose surface, split along the sides. Apothecia large, pale brown, always growing on the top of the podetia. Primary squamules shell-like, thick, and convex. Fumarprotocetraric acid contained in thallus. This is the first record of this species in Korea.

Chemical Ingredients of Cordyceps militaris

Medicinal mushrooms, including Cordyceps militaris, have received attention in Korea because of their biological activities. In the fruiting body and in corpus of C. militaris, the total free amino acid content was 69.32 mg/g and 14.03 mg/g, respectively. In the fruiting body, the most abundant amino acids were lysine, glutamic acid, proline and threonine. The fruiting body was rich in unsaturated fatty acids, which comprised about 70% of the total fatty acids. The most abundant unsaturated acid was linoleic acid. There were differences in adenosine and cordycepin contents between the fruiting body and the corpus. The adenosine concentration was 0.18% in the fruiting body and 0.06% in the corpus, and the cordycepin concentration was 0.97% in the fruiting body and 0.36% in the corpus.

Favorable Culture Conditions for Mycelial Growth of Korean Wild Strains in Ganoderma lucidum

Ganoderma lucidum (Fr.) Karst (Polyporaceae), belonging to basidiomycota, is one of the most famous medicinal mushrooms. This study was carried out to investigate favorable mycelial growth conditions, such as pH, temperature, growth media, carbon sources and nitrogen sources of Korean strains in G. lucidum. The most suitable temperature for the mycelial growth was obtained at 30degrees C. In general, optimal temperature range for the mycelial growth was found at 25~30degrees C. This Mushroom has a broad pH range (5~9) for its mycelial growth and mostly favorable growth was found at pH 5. Generally, Hamada, Glucose peptone, YM, Mushroom complete and Lilly media were the most suitable for the mycelial growth of G. lucidum. Among 10 different carbon sources, dextrin, galactose and fructose were best but the rest of other carbon sources also facilitated the growth of mycelia. The most suitable nitrogen sources were ammonium acetate, glycine, arginine and calcium nitrate, but to a certain extent, all of the supplemented nitrogen sources also stimulated the mycelial growth.

Physicochemical Requirement for the Vegetative Growth of Schizophyllum commune Collected from Different Ecological Origins

Schizophyllum commune is an edible and medicinal mushroom widely distributed in the world. The optimal growth conditions for the mycelia of 10 strains of the fungus were investigated. The temperature suitable for the mycelial growth and density was obtained at 30~35degrees C. Among the tested conditions, the minimum mycelial growth was found at 15degrees C. In case of pH, the most favorable growth was found at pH 5. The results indicated that this mushroom well adapted to high temperature and low pH for its mycelial growth. Considering growth phenotype of mycelia, Hamada, Hennerberg, PDA and YM were the most suitable and Lilly, Glucose triptone, Glucose peptone and Hoppkins were the most unfavorable among tested media for the mycelial growth of S. commune. Out of tested carbon sources, dextrin and fructose were the most suitable and lactose, mannose and sorbitol were the unsuitable for the fungus. Compact mycelial density was obtained from most of the carbon sources. Among used nitrogen sources, calcium nitrate, potassium nitrate and alanine were the most appropriate and the most incompatible were ammonium phosphate, histidine, urea and arginine for mycelial growth of S. commune on the culture media. Calcium nitrate, histidine and potassium nitrate showed moderately thin or thin, and rest of nitrogen sources showed compact or moderately compact mycelial density.

Low-density lipoprotein protects Vibrio vulnificus-induced lethality through blocking lipopolysaccharide action

Lipoprotein plays a role in the host defense against bacterial infection, and its serum level has been demonstrated to be an important prognosis factor of survival. We have previously demonstrated that LDL directly inactivates the hemolytic activity of Vibrio vulnificus cytolysin (VVC) in vitro. The object of this study was therefore to examine whether the LDL-mediated inactivation of VVC leads to protection against lethal infection of V. vulnificus in vivo, using wild and VVC-deficient V. vulnificus strains. Unexpectedly, we found that LDL protects mouse lethality induced by VVC-deficient as well as wild V. vulnificus strain. We also demonstrated that LDL blocks V. vulnificus LPS-induced lethality in mice. These results suggest that LDL preferentially act on endotoxin rather than exotoxin in the protection against V. vulnificus-induced mice lethality.

The Artificial Cultivation of Oudemansiella mucida on the Oak Sawdust Medium

To produce fruiting bodies of Oudemansiella mucida, porcelain fungus, on the oak sawdust medium, additives suitable for the mycelial growth and fruiting body formation were screened. In general, the mycelial growth of the three strains of O. mucida used in this study have been good on oak sawdust mixed rice bran of 20~30%. The mycelia incubated in potato dextrose broth for 7 days were inoculated on oak sawdust medium supplemented with various ratios of rice bran and incubated for 30 days at 25degrees C in the dark condition until the mycelia of O. mucida fully colonized the media from top to bottom. Then, top surface of the media in the bottles were horizontally scratched with a spatula and filled with tap water for 3 hours. To induce the primordial formation of O. mucida, the bottles were transferred to the mushroom cultivating room under 12 hrs of light (350 lux) and dark condition with relative humidity of 95% at 17degrees C. The primordia of O. mucida were formed on the surface of oak sawdust media after 7 days of incubation. The mature fruiting bodies were observed 5 days after primordial formation. The fruiting bodies O. mucida were formed on oak sawdust medium mixed with 5 to 30% rice bran. However, abundant fruiting-bodies of O. mucida were produced in oak sawdust medium supplemented with 20% rice bran. This is the first report associated with an artificial fruiting body production of O. mucida in Korea.

A Case of Anisakiasis Concurrently Invading Esophagus and Stomach, and Another Case of Esophageal Anisakiasis / 대한소화기내시경학회지

Human anisakiasis may occur after ingestion of raw marine fish infected with the nematode larvae of Anisakidae. Clinical symptoms such as cramping abdominal pain, nausea, vomiting, diarrhea and epigastric fullness, usually develop within 12 hours after having eaten infected raw sea fish. Anisakiasis is most commonly found in the stomach, and is rarely identified in the small intestine, large intestine, and esophagus. We report two cases of of anisakiasis, one with concurrent invasion of the stomach and esophagus, and the other case with esophageal anisakiasis. Both were treated by endoscopic extraction of the larvae.

A Case of Nodular Fasciitis Misdiagnosed as Baker's Cyst in a Patient with Rheumatoid Arthritis / 대한류마티스학회지

Nodular fasciitis is rare and benign fibroblastic proliferative disease which tends to be confused microscopically with spindle cell sarcoma. It is a distinctive lesion and a very important one because of its ability to simulate a malignant process. Histopathologically, nodular fasciitis can be grouped into three subtypes based on their relation with the fascia: subcutaneous, fascial, intramuscular. We report a case of nodular fasciitis misdiagnosed as Baker's cyst in a patient with rheumatoid arthritis.

Morphological Characteristics of Pseudosclerotia of Grifola umbellata in In Vitro

The present study was carried out to investigate morphological characteristics of pseudosclerotia of Grifola umbellata formed by artificial cultures. Isolate G. umbellata DUM GUS-01 was obtained from sclerotium cultivated in field. The fungal isolate was cultured on PDYM broth, PDYMA(potato dextrose yeast malt agar) and oak sawdust media at 20degrees C under the dark condition. G. umbellata DUM GUS-01 showed a volumetric increment of fungal lumps rather than mycelial growth. Particularly, G. umbellata DUM GUS-01 produced a large amount of melanin pigments in all culture treatments. The color of the fungal mass has been changed into grey gradually, and then formed melanized rind-like structure on its superficial part. The fungal structures which were covered with melanized rind-like layer were named as pseudosclerotia of G. umbellata. The pseudosclerotia of G. umbellata DUM GUS-01 formed a new white mycelial mass, which was swollen out of the melanized rind structure for its volumetric increment. When the pseudosclerotia were sectioned, their structure was discriminated from two structures such as a melanized rind-like structure layer formed by aggregation of aged mycelia and a white mycelial mass with high density. As results of scanning electron microscopic examination, the pseudosclerotia of G. umbellata DUM GUS-01 which were formed in in vitro conditions were similar to the sclerotia of G. umbellata cultivated in natural conditions except for the crystals formed in medula layer of natural sclerotia. Although size, solidity of rind structure and mycelial compactness of pseudosclerotia were more poor than those of natural sclerotia, the morphological structure and growth pattern of pseudosclerotia were very similar to those of natural sclerotia. Therefore, it is probable to induce pseudosclerotia to sclerotia of G. umbellata in in vitro conditions. Consequently, it seems that the induced pseudosclerotia can be used as inoculum sources to substitute natural sclerotia in field cultivation.

Phase II Study of Concurrent Chemotherapy with Etoposide and Cisplatin (EP) and Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer / 결핵

BACKGROUND: Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC), however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, arid survival of concurrent chemotherapy with etoposide and cisplatin(EP) arid radiation therapy for unresectable stage III NSCLC. METHODS: Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without, malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide arid cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. RESULTS: Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient The median survival was l2.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia(> or = grade 3,46%) Thrombocytopenia over grade 3 was found in 1%. Radiation pneumonitis occurred in 13 patients(46%). CONCLUSION: Concurrent chemotherapy(EP) pins radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

Three Cases of Interstitial Pneumonitis Developed after Anticancer Chemotherapy Containing Cyclophosphamide / 대한내과학회지

Development of diffuse pulmonary infiltrates in patients receiving chemotherapy is a major diagnostic challenge. Diffuse pulmonary infiltrates may be due to infection, pulmonary hemorrhage, pulmonary edema or drug-induced lung injury. Among these, pulmonary toxicity caused by antineoplastic agent is being recognized more frequently. Cyclophosphamide, an alkylating cytotoxic drug, is used widely in the treatment of malignancies including lymphoma. The incidence of pulmonary toxicity is probably less than 1 percent, and its relation with total dosages and schedule of the drug is not yet defined. The typical pictures of cyclophosphamide-induced pulmonary toxicity are non-productive cough, dyspnea, fever, hypoxemia with respiratory alkalosis and interstitial pneumonitis. However, relatively infrequent pulmonary toxicity of cyclophosphamide and frequent development of infectious pulmonary infiltrate in the patients treated with chemotherapy may hamper the early diagnosis of cyclophosphamide toxicity. Interstitial pattern and unresponsiveness to antibiotics of the pneumonitis might be the clues of suspicion. The best ways to treat the patients with cyclophosphamide toxicity are early diagnosis, discontinuation of the drug and early corticosteroid trial, although usefulness of steroid has not been firmly established. Recently, we experienced three cases of interstitial pneumonitis developing during cyclophosphamide-containing chemotherapy for non-Hodgkin's lymphoma in the absence of neutropenia or thrombocytopenia. Early use of corticosteroid in later two cases could resolve the pulmonary complication completely, whereas the pneumonitis failed to improve in spite of the massive use of multiple antibiotics in the first case.