Cyclobutane-Containing Meroditerpenoids, (+)-Isoscopariusins B and C: Structure Elucidation and Biomimetic Synthesis.

(+)-Isoscopariusins B (1) and C (2), two meroditerpenoids containing a 6/6/4 tricyclic carbon skeleton and seven continuous stereocenters, were identified from Isodon scoparius. The structures were determined by nuclear magnetic resonance analysis and concise biomimetic syntheses from readily available alkene 5 in seven and six steps, respectively. An intermolecular [2+2] photocycloaddition with cooperative catalysis of a Lewis acid and an Ir photocatalyst was used to construct a cyclobutane core with four stereogenic centers.

Repellent, larvicidal and adulticidal activities of essential oil from Dai medicinal plant Zingiber cassumunar against Aedes albopictus.

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm2). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (-)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm2). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC50 (50% lethal concentration) of 44.9 µg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC50 of 5.44%, while (-)-terpinen-4-ol showed significant adulticidal activity with a LC50 of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (-)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (-)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.

The best choices: the diversity and functions of the plants in the home gardens of the Tsang-la (Motuo Menba) communities in Yarlung Tsangpo Grand Canyon, Southwest China.

BACKGROUND: Home garden is identified as a kind of small-scale land-use system which is used to manage and cultivate useful plants by local people, and home gardens can provide various plant products and services. Investigating home gardens was regarded as an effective way to understand the biodiversity-related local knowledge and culture of native people in Ethnobiology and Ethnoecology. Home garden is important in less developed and remote areas. The grand canyon of Yarlung Tsangpo is designed as one of the biodiversity hotspots of China, and it is one of the most remote regions of China, because of the rough traffic conditions. The aim of the present study is to collect, record, and document the plants and their local knowledge and functions in the local home gardens, then attempt to answer the question: "why local people selected these plants?" MATERIAL AND METHODS: The study area was in Beibeng Township of Motuo County in the grand canyon of Yarlung Tsangpo. Observation and semi-structure interviews with informed consent were used to collect data in field study. All information was collected and organized, then documented based on "ethno-species" as a fundamental unit. All of the information of local use and knowledge were organized as the list of "use-report" for quantitative analysis, and the local uses of plants were merged into 14 use categories. Frequency of citation (FC), relative frequency of citation (RFC), cultural importance index (CI), and cultural value index (CV) were used in quantitative analysis. Besides, the Jaccard Index was used to compare the similarity in plant species selection among different communities. RESULTS: A total of 78 home gardens in the 9 communities of Beibeng Township were visited, and 196 ethno-species were collected. These ethno-species were identified into 188 Botanical taxa. A total of 87 home garden owners as informants were interviewed in the present study, and they provided 625 use-reports to us. The top 5 important plants were Su-lan-tsao (Dendrobium nobile), Sa-ga (Zingiber officinale), Soe-lu (Capsicum annuum), Snying-pa (Citrus medica), and Kham-pu (Prunus persica), according to the quantitative analysis. The most citied use-category was "vegetable," followed by "ornamental plant," "medicine," and "fruit." The altitude might be the most important impact factor of the plant diversity and composition of home gardens, and the traffic conditions, local terrain, also impact the plant diversity and composition of home gardens. CONCLUSION: In remote areas such as the Yarlung Tsangpo Grand Canyon, the plants in home gardens are important sources of plant products such as foods, herbal medicines, and fibers to support daily lives. The local home gardens in Tsang-la communities had high diversity of plants, and these plants provided many functions and services to support daily lives of local people. Local plant knowledge, including the features, life forms, habits, habitats, and use values of plants, were the summary of the understanding of local people to their surrounding plant worlds. Local people selected appropriate plants to cultivate and manage in their home gardens under the guidance of the local plant knowledge. That is the answer to the question "why local people selected these plants?"

New Sweet-Tasting C21 Pregnane Glycosides from the Roots of Myriopteron extensum.

To investigate the sweet-tasting components in the roots of Myriopteron extensum, the phytochemical study of its roots was conducted, which led to the discovery of 12 new C21 pregnane glycosides (extensumside M-X, 1-12) and two known ones (extensumside C and extensumside E, 13-14). Their chemical structure elucidation was accomplished by means of spectroscopic methods: IR, UV, ESI-MS, and NMR (1H NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, HSQC-TOCSY, and ROESY), as well as the chemical evidence. Sensory analysis of these compounds revealed that nine of them (1, 3, 4, 5, 6, 7, 8, 13, and 14) are highly sweet-tasting compounds. Their sweetness intensities are 25 to 400 times greater than that of sucrose. Analysis of the structure-activity relationship (SAR) indicated that the sweet intensities of the isolated compounds are closely related to the aglycone 3ß,16α-dihydroxy-pregn-5-en-20-one, the number and type of the monosaccharide in the sugar chain linked to C-3 and C-16 and the position of the mBe group.

Separation of oxidized variants of a monoclonal antibody by anion-exchange.

Monoclonal antibodies are subject to a variety of degradation mechanisms, therefore orthogonal techniques are required to demonstrate product quality. In this study, the three individual antibodies comprising a multi-antibody drug product, XOMA 3AB were evaluated by both cation-exchange (CEX) and anion-exchange chromatography (AEX). In contrast to CEX analysis which showed only a single, broad peak for the force-oxidized antibodies, AEX analysis of Ab-A (pI=7.6) revealed two more basic peaks. Ab-B (pI=6.7) bound but exhibited only a single major peak while Ab-C (pI=8.6) flowed through. Peptide mapping LC/MS analysis of the isolated Ab-A fractions demonstrated that the basic peaks resulted from oxidation in a complementary determining region (CDR). Differential scanning calorimetry (DSC) analysis of the oxidized Ab-A species showed a decrease in the Fab melting point for the oxidized species consistent with unfolding of the molecule. Greater/lesser surface exposure of ionic residues resulting from a conformational change provides a likely explanation for the dramatic shift in retention behavior for the Ab-A oxidized variants. Peptide mapping analysis of the Ab-B antibody showed, in contrast to Ab-A, no detectable CDR oxidation. Hence, the lack of separation of oxidized variants in Ab-B can be explained by the absence of CDR oxidation and the associated changes in secondary/tertiary structure which were observed for oxidized Ab-A. In summary, anion-exchange HPLC shows potential as an orthogonal analytical technique for assessing product quality of monoclonal antibody therapeutics. In the case of the XOMA 3AB drug product, two of the antibodies bound and one, Ab-A, exhibited separation of CDR oxidized variants.

[Arrhythmia after a positive head-up tilt table test].

OBJECTIVE: to study the characteristics of arrhythmia after a positive head-up tilt table test (HUTT). METHODS: head-up tilt table test (BHUT) or sublingual nitroglycerin-provocation head-up tilt table test (SNHUT) were performed in 1374 patients at the Second Xiangya Hospital of Central South University from March of 2001 to August of 2009. Arrhythmias were recorded in 169 patients after a positive HUTT [57 male, age 6 - 65 years, 86 children < 18 years, mean age (23.1 ± 14.8) years]. RESULTS: arrhythmias developed in 75 patients (44.38%) post a positive BHUT and in 94 patients (55.62%) post a positive SNHUT. Major types of arrhythmias were sinus bradycardia (143/169, 84.62%), junctional escape rhythm (55/169, 32.54%) and sinus arrest (26/169, 15.38%). Sinus bradycardia was more common in adult (P < 0.01). Occurrence of junctional escape rhythm and sinus arrest was not affected by age, gender and test mode. Arrhythmia and the manifestation of syncope or pre-syncope occurred simultaneously in 77 (45.56%) patients and mainly in BHUT, while arrhythmia appeared later than the syncope manifestation in 92 (54.44%) patients and mainly in SNHUT (P < 0.05). Arrhythmia and blood pressure reduction occurred simultaneously in 84 (53.50%) cases and mainly in BHUT, while arrhythmia appeared later than reduction of blood pressure in 73 (46.50%) cases and mainly in SNHUT (P < 0.01). CONCLUSIONS: (1) the common types of arrhythmia were sinus bradycardia, junctional escape rhythm and sinus arrest after a positive HUTT. Occurrence of sinus arrest was not affected by age, gender and test mode. (2) In BHUT, arrhythmia occurred mostly simultaneously with the manifestation of syncope or pre-syncope and blood pressure reduction, while arrhythmia appeared later in SNHUT.

[Clinical analysis of vasovagal syncope in children].

OBJECTIVE: To study the changes in clinical features of vasovagal syncope (VVS) in children. METHODS: From January 2000 to September 2009, 841 children with unexplained syncope or prodromata were enrolled. They were assigned to two groups according to the period of visiting hospital: group A (from January 2000 to December 2004, n=129) and group B (from January 2005 to September 2009, n=712). They were assigned to three age groups: 4-6 years old, 7-10 years old and 11-18 years old. A head-up tilt table test (HUTT) was performed on all the subjects. RESULTS: The total positive rate of HUTT was 45.3% (381/841). Compared with that in group A, the positive rate of HUTT in group B increased significantly (47.5% vs 33.3%; P<0.05). The positive rate of HUTT in female children was significantly higher than that in male children (49.3% vs 37.9%; P<0.05). The positive rate of HUTT increased with age and it was the highest in children at age of 11-18 years (49.2%), followed by in children at age of 7-10 years (44.1%) and 4-6 years (37.1%) (P<0.05). The children at age of 7-10 years and 11-18 years from group B showed significantly higher positive rate of HUTT than those from group A (46.2% vs 27.8%; 54.0% vs 32.6%, P<0.05). Vasodepressor type was the most common response type (70.9%) shown by HUTT compared with mixed type (25.5%) and cardioinhibitory type (3.6%) (P<0.05). The proportion of children with vasodepressor response type in group B was significantly higher than that in group A (72.5% vs 58.1%; P<0.05). CONCLUSIONS: There were obvious changes in the prevalence of VVS and response types before and after five years, suggesting that the development of VVS may be attributed to many factors, such as social factors, mental factor and life style.

[Efficacy of midodrine hydrochloride in the treatment of children with vasovagal syncope].

OBJECTIVE: To explore the efficacy of midodrine hydrochloride in the treatment of vasovagal syncope (VVS) in children. METHODS: Forty-eight children with unexplained syncope and prodromata (21 males, 27 females, aged 6 -17 years, mean 11 years +/- 3 years) were randomly assigned into 3 groups. They were health education group, cresol group and midodrine hydrochloride group respectively. Cresol group was comprised of children given cresol as first-line therapy in addition to health education and midodrine hydrochloride group patients given midodrine hydrochloride on the basis of cresol group. Repeated head-up tilt testing (HUTT) and follow-ups of at least 6 months were conducted to evaluate the therapeutic efficacy, side effects of midodrine hydrochloride and hemodynamic changes in treating pediatric VVS. RESULTS: (1) The HUTT-based effective rate of 3 group was 20.0% (2/10), 60.9% (14/23) and 80.0% (12/15) respectively. It was significantly higher in cases of midodrine hydrochloride group and cresol group than that of health education group (P < 0.05). However,there was no significant difference in the HUTT-based effective rate between cresol group and midodrine hydrochloride group (P > 0.05). (2) During the follow-up period, the recurrence rate of syncope was significantly lower in midodrine hydrochloride group than in other two groups (P < 0.05). However, there was no significant difference in the recurrence rate of syncope between health education and cresol groups (P > 0.05). (3) There was no statistic difference in supine hemodynamic indices (HR, SBP, DBP) between before and after treatment in 3 groups. After midodrine therapy, the effects of midodrine upon changes in systolic and diastolic pressures and heart rate, between upright beginning and supine positions, were statistically significant (P <0.05). CONCLUSION: Health education and cresol are conventional therapies for pediatric VVS. The efficacy can be enhanced by supplementing midodrine hydrochloride. Such a regimen is effective and safe in treating pediatric VVS.

[Clinical characteristics in adults and children with vasovagal syncope].

OBJECTIVE: To analyze the clinical characteristics in adults and children with vasovagal syncope (VVS). METHODS: Clinical data including head-up tilt table (HUTT) results were analyzed and compared in 136 children (mean age 12.3 +/- 2.7 years, 50 boys, 86 girls) and 119 adults (mean age 36.4 +/- 14.0 years, 29 men, 90 women) with VVS. RESULTS: (1) There were more female VVS patients in adults group than that in children group (male and female ratio: children group 1:1.7 and adults group 1:3.1, P = 0.033) in this cohort. (2) The incidence of chest distress in adults group was significantly higher than that in children group [45.4 (54/119) vs. 27.2% (37/136), P = 0.003] while the incidence of headache [10.9% (13/119) vs. 20.6% (28/136), P = 0.036] and abdominal pain in children group was significantly higher than that in adults group [7.6% (9/119) vs. 19.1% (26/136), P = 0.008]. (3) Incidences of muggy environment [22.8% (26/114) vs. 12.5% (17/136), P = 0.032] and urination VVS [9.7% (11/114) vs. 1.5% (2/136), P = 0.004] were significantly higher in adults group than those in children group. (4) The mean time of mixed response vasogal episode in adults group was significantly longer than that in children group in sublingual nitroglycerin head-up tilt table test (SNHUT) stage (5.04 +/- 2.27 min vs. 3.50 +/- 1.24 min, P = 0.036). CONCLUSIONS: The incidences of chest distress, muggy environment and urination VVS were more often and the mean time of vasogal episode of mixed response in SNHUT stage was longer in adults VVS while the incidence of abdominal pain and headache was higher in children VVS patients compared to adults VVS patients.