Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule, real-time sequencing.

Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and psbA-trnH regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.

Economic botany collections: A source of material evidence for exploring historical changes in Chinese medicinal materials.

ETHNOPHARMACOLOGICAL RELEVANCE: Many Chinese medicinal materials (CMMs) have changed over centuries of use, particularly in terms of their botanical identity and processing methods. In some cases, these changes have important implications for safety and efficacy in modern clinical practice. As most previous research has focused on clarifying the evolution of CMMs by analyzing traditional Chinese materia medica ("bencao") literature, assessments of historical collections are needed to validate these conclusions with material evidence. AIM OF THE STUDY: Historical collections of Chinese medicines reveal the market materials in circulation at a given moment in time, and represent an underexploited resource for analyzing the evolution of Chinese herbal medicines. This study compares specimens from a rare collection of CMMs from the 1920s with contemporary market materials; by highlighting examples of changes in botanical identity and processing that remain relevant for safe clinical practice in the modern era, this work aims to stimulate further research into previously unexplored historical collections of Chinese medicines. MATERIALS AND METHODS: 620 specimens of CMMs that were collected from Chinese pharmacies in the Malay peninsula in the 1920s were examined macroscopically and compared with current pharmacopoeia specifications and authentic contemporary samples. These historical specimens, which are stored in the UK in the Economic Botany Collections (EBC) of Royal Botanic Gardens Kew, were morphologically examined, photographed, and compared to authentic CMMs stored at the Bank of China (Hong Kong) Chinese Medicines Center at Hong Kong Baptist University, as well as authentic herbarium-vouchered specimens from the Leon Collection (LC) at the Kew EBC. Case studies were selected to illustrate examples of historical changes in botanical identity, used plant parts, and processing methods. RESULTS: This investigation confirmed that confusion due to shared common names and regional variations in the botanical identity of certain CMMs has been a persistent issue over time. Additionally, historical changes in processing methods and the plant parts used were observed for some CMMs. In some cases, these changes have direct implications for the safe clinical practice of Chinese medicine. CONCLUSIONS: This preliminary assessment illustrated the significant potential of collections for clarifying historical changes in CMMs. More research is needed to investigate pre-modern collections of CMMs, including a more comprehensive assessment of the holdings in the Kew EBC and other European collections that have not yet been explored from the perspective of Chinese medicine.

A renaissance in herbal medicine identification: from morphology to DNA.

Numerous adverse reactions have arisen following the use of inaccurately identified medicinal plant ingredients, resulting in conditions such as aristolochic acid nephropathy and herb-induced poisoning. This problem has prompted increased global concern over the safety of herbal medicines. DNA barcoding, a technique aiming at detecting species-specific differences in a short region of DNA, provides a powerful new tool for addressing this problem. A preliminary system for DNA barcoding herbal materials has been established based on a two-locus combination of ITS2+psbA-trnH barcodes. There are 78,847 sequences belonging to 23,262 species in the system, which include more than 95% of crude herbal drugs in pharmacopeia, such as those of China, Japan, Korea, India, USA, and Europe. The system has been widely used in traditional herbal medicine enterprises. This review summarizes recent key advances in the DNA barcoding of medicinal plant ingredients (herbal materia medica) as a contribution towards safe and efficacious herbal medicines.

Rapid sequential injections of hyperpolarized [1-¹³C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer.

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of (13)C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-(13)C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-(13)C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in (13)C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.

Mixing method affects elution and strength of high-dose ALBC: a pilot study.

BACKGROUND: High-dose antimicrobial-loaded bone cement (ALBC) is used to treat orthopaedic infections. High-dose ALBC is not commercially available and requires surgeon directed formulation, and there are several different methods used to mix high-dose ALBC. QUESTIONS/PURPOSES: We asked whether the mixing method affected antimicrobial elution and mechanical properties of high-dose ALBC. METHODS: ALBC was formulated with Simplex P bone cement and 10 g of vancomycin per batch using one of three mixing methods: (1) hand-stirred using a standard bowl and spatula, (2) bowl-mixed using a mechanical mixing bowl, and (3) dough-phase mixing where the vancomycin was left in chunks (1-5 mm) and folded into the cement during the dough phase after adding the monomer. We eluted 45 standardized test cylinders (15 per mixing technique) for 30 days under infinite sink conditions. We tested 135 (45 per mixing method) similarly eluted cylinders in axial compression to failure. RESULTS: Dough-phase mixing lead to greater antimicrobial delivery, but lower compressive strength than the hand-stirred or bowl-mixed methods. Dough-phase cement released 18,570 lg of vancomycin versus 11,731 for hand-stirred and 7700 µg for bowl mixed. Compressive strength for dough-phase mixing after 30 days of elution was 36 MPa, while both hand-stirred and bowl mixed cements were 56 MPa. CONCLUSIONS: Performance of high-dose ALBC was affected by mixing method. Dough-phase mixing led to greater antimicrobial delivery, but caused greater loss in compressive strength.

Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica.

ETHNOPHARMACOLOGICAL RELEVANCE: Studies on traditional Chinese medicine (TCM), like those of other systems of traditional medicine (TM), are very variable in their quality, content and focus, resulting in issues around their acceptability to the global scientific community. In an attempt to address these issues, an European Union funded FP7 consortium, composed of both Chinese and European scientists and named "Good practice in traditional Chinese medicine" (GP-TCM), has devised a series of guidelines and technical notes to facilitate good practice in collecting, assessing and publishing TCM literature as well as highlighting the scope of information that should be in future publications on TMs. This paper summarises these guidelines, together with what has been learned through GP-TCM collaborations, focusing on some common problems and proposing solutions. The recommendations also provide a template for the evaluation of other types of traditional medicine such as Ayurveda, Kampo and Unani. MATERIALS AND METHODS: GP-TCM provided a means by which experts in different areas relating to TCM were able to collaborate in forming a literature review good practice panel which operated through e-mail exchanges, teleconferences and focused discussions at annual meetings. The panel involved coordinators and representatives of each GP-TCM work package (WP) with the latter managing the testing and refining of such guidelines within the context of their respective WPs and providing feedback. RESULTS: A Good Practice Handbook for Scientific Publications on TCM was drafted during the three years of the consortium, showing the value of such networks. A "deliverable - central questions - labour division" model had been established to guide the literature evaluation studies of each WP. The model investigated various scoring systems and their ability to provide consistent and reliable semi-quantitative assessments of the literature, notably in respect of the botanical ingredients involved and the scientific quality of the work described. This resulted in the compilation of (i) a robust scoring system and (ii) a set of minimum standards for publishing in the herbal medicines field, based on an analysis of the main problems identified in published TCM literature. CONCLUSION: Good quality, peer-reviewed literature is crucial in maintaining the integrity and the reputation of the herbal scientific community and promoting good research in TCM. These guidelines provide a clear starting point for this important endeavour. They also provide a platform for adaptation, as appropriate, to other systems of traditional medicine.

Amphotericin B delivery from bone cement increases with porosity but strength decreases.

BACKGROUND: Amphotericin B is a highly hydrophobic antifungal used for orthopaedic infections. There is disagreement about whether amphotericin B is released when it is loaded in polymethylmethacrylate (PMMA). It is unknown how much a poragen will increase amphotericin B release or decrease the compressive strength of the PMMA. QUESTIONS/PURPOSES: We therefore measured amphotericin B release and the compressive strength of amphotericin B loaded bone cement with and without adding high-dose poragen. METHODS: Antifungal-loaded bone cement was formulated with Simplex P cement and 200 mg amphotericin B with and without 10 g cefazolin (poragen) per batch. Twenty standardized test cylinders were eluted in deionized water for each formulation. Cumulative amphotericin B mass and compressive strength were measured. Data were analyzed using repeated-measures analysis of variance. RESULTS: Antifungal-loaded bone cement (ALBC) with 10 g poragen delivered more amphotericin B than ALBC containing amphotericin B alone by Day 15, 12.76 µg/cylinder (0.5%) versus 1.74 µg/cylinder (0.04%), respectively. With amphotericin B alone, compressive strength was unchanged and compressive strength did not decrease during elution. Adding 10 g poragen to ALBC with 200 mg amphotericin B decreased the compressive strength and compressive strength decreased further during elution, 80, 61, and 46 MPa at 0, 1, and 30 days, respectively. CONCLUSIONS: Amphotericin B is released in very small amounts from antifungal-loaded bone cement. Release can be increased by adding high-dose poragen, but compressive strength decreases sufficiently to limit its use for implant fixation.

Surfactant-stabilized emulsion increases gentamicin elution from bone cement.

BACKGROUND: Liquid antimicrobial use for antimicrobial-loaded bone cement is limited because of decreased strength and small volume that can be loaded. Emulsifying the liquid antimicrobial into the monomer may address both issues. QUESTIONS/PURPOSES: We determined the effect of using a surfactant-stabilized emulsion on antimicrobial release, compressive strength, and porosity. METHODS: We made 144 standardized test cylinders from emulsified antimicrobial-loaded bone cement (three batches, 72 cylinders) and control antimicrobial-loaded bone cement made with antimicrobial powder (three batches, 72 cylinders). For each formulation, five specimens per batch (n = 15) were eluted in infinite sink conditions over 30 days for gentamicin delivery; five specimens per batch were axially compressed to failure after elution of 0, 1, and 30 days (n = 45); and two noneluted specimens and two gentamicin delivery specimens from each batch (n = 12) were examined under scanning electron microscopy for porosity. Antimicrobial release and compressive strength were compared across cement type and time using repeated-measures ANOVA. RESULTS: Emulsified antimicrobial-loaded bone cement released four times more antimicrobial than control. Compressive strength of emulsified antimicrobial-loaded bone cement was less than control before elution (58.1 versus 81.3 MPa) but did not decrease over time in elution. Compressive strength of control antimicrobial-loaded bone cement decreased over 30 days in elution (81.3 versus 73.9 MPa) but remained stronger than emulsified antimicrobial-loaded bone cement. Porosity was homogeneous, with pores ranging around 50 µm. CONCLUSIONS: Emulsified antimicrobial-loaded bone cement has homogeneous porosity with increased drug release but a large loss of strength. CLINICAL RELEVANCE: Liquid antimicrobials are released from emulsified antimicrobial-loaded bone cement, but increased strength is needed before this method can be used for implant fixation.

Synthesis and characterization of thermo-sensitive radio-opaque poly(N-isopropylacrylamide-co-PEG-2-iodobenzoate).

Radiopacity is required for embolic materials to be monitored by angiography during embolization. Covalently bound radio-opaque biomaterials would be ideal for embolization. Poly(N-isopropylacrylamide-co-PEG-acrylate) modified with 2-iodobenzoyl chloride was synthesized and characterized by (1)H-NMR, differential scanning calorimetry and X-ray opacity. Poly(N-isopropylacrylamide-co-PEG-2-iodobenzoate) shows radiopacity, as well as thermo-sensitivity. Cytotoxicity testing on these co-polymers shows little cytotoxicity. Phase-transition temperature and radiopacity varied according to the content of NIPAAm and 2-iodobenzoate. Increasing the content of 2-iodobenzoate raised the radiopacity and lowered the LCST.

Comparación de la calidad de vida entre médicos graduados en el Perú que migraron al extranjero y los que permanecieron en el país / Perceived quality of life comparison between medical graduates from Peru who migrated and those who stayed in their home country

Objetivo: Comparar la calidad de vida (CDV) de los egresados de una Escuela de Medicina peruana que migraron al extranjero y de los que permanecieron en el país. Material y método: Se utilizó un cuestionario basado en una combinación de dos herramientas para medir la CDV de proveedores de salud previamente validadas, para evaluar auto-satisfacción (grupo A), las relaciones interpersonales y sociales (grupo B) y los niveles de satisfacción personal (grupo C). Es cuestionario se envió por correo electrónico a los graduados de la Universidad Peruana Cayetano Heredia. Resultados: La tasa de respuesta fue 35%. Los niveles de ingreso económico fueron significativamente menores en los médicos que permanecieron en el Perú en comparación con los que migraron. En muy pocas preguntas se encontró diferencia significativa. En el grupo A, los médicos que migraron percibieron una CDV significativamente mayor solo en la expectativa de futuro. En el grupo B, esto se alcanzó diferencias sólo en el grado de apoyo y el nivel de conflicto entre colegas , y en el grupo C, en el nivel de información recibida acerca de los resultados de su trabajo (ôfeedbackõ), el esfuerzo físico del trabajo diario (estrés físico), las oportunidades de expresar lo que se piensa y necesita, el esfuerzo del hospital para mejorar la CDV de sus trabajadores, el entrenamiento necesario para realizar el trabajo diario, y la variedad en el trabajo. Los médicos que migraron percibieron una mayor aceptación en la profesión, en la sociedad en general y dentro de la comunidad donde viven. De manera significativa más médicos que migraron no tenían intenciones de cambiar sus niveles actuales de vida. Conclusiones: La CDV percibida de los médicos estudiados fue similar en la mayoría de preguntas examinadas entre ambos grupos, a pesar de la marcada diferencia encontrada en los niveles de ingreso económico.

Objective: To compare the quality of life (QOL) of the graduated from a Peruvian medical school who migrated abroad and those who remained in the country. We also intended to address the level of integration of Peruvian international medical graduates (IMGs) into the United States (US). Material and methods: A combination of two previously validated tools designed to measure QOL of health care practitioners (HCPs) was used to create a survey, including questions that analyzed self-satisfaction (group A), interpersonal/social relationships (Group B) and professional satisfaction (Group C), which was e-mailed to graduates from a Peruvian Medical School. Results: The response rate was 35%. Income levels were significantly lower for HCPs practicing in Peru than those practicing abroad. Very few question items reached statistical significant differences between groups. In group A, IMGs who migrated perceived a significantly higher QOL only in the perception of their future. In group B, was achieved only in the peer support and the conflict level with coworkerÆs categories. In group C, only in the work feedback, job physical discomfort, expression opportunities, hospital attempts to improve the QOL of their position, necessary training for job performance and work variety categories. However, of 41/44 items showed a better (more satisfied) response from the abroad group, of which 13 achieve statistical significance (8 at the 1% level). IMGs practicing abroad perceived a high acceptance into the foreign profession, society and living community. Significantly most IMGs do not intend to change their current status. Conclusions: Very few significant differences were noted in the perceived QOL of physicians between groups, in spite of a marked income discrepancy. However, there was a clear trend for dissatisfaction in the Peru group on several important items that, without reaching statistical significance, may indicate the adverse effect of Peruvian...

Validation of the ITS2 region as a novel DNA barcode for identifying medicinal plant species.

BACKGROUND: The plant working group of the Consortium for the Barcode of Life recommended the two-locus combination of rbcL+matK as the plant barcode, yet the combination was shown to successfully discriminate among 907 samples from 550 species at the species level with a probability of 72%. The group admits that the two-locus barcode is far from perfect due to the low identification rate, and the search is not over. METHODOLOGY/PRINCIPAL FINDINGS: Here, we compared seven candidate DNA barcodes (psbA-trnH, matK, rbcL, rpoC1, ycf5, ITS2, and ITS) from medicinal plant species. Our ranking criteria included PCR amplification efficiency, differential intra- and inter-specific divergences, and the DNA barcoding gap. Our data suggest that the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA represents the most suitable region for DNA barcoding applications. Furthermore, we tested the discrimination ability of ITS2 in more than 6600 plant samples belonging to 4800 species from 753 distinct genera and found that the rate of successful identification with the ITS2 was 92.7% at the species level. CONCLUSIONS: The ITS2 region can be potentially used as a standard DNA barcode to identify medicinal plants and their closely related species. We also propose that ITS2 can serve as a novel universal barcode for the identification of a broader range of plant taxa.

Distribution of EFHC1 or Myoclonin 1 in mouse neural structures.

EFHC1, a gene mutated in juvenile myoclonic epilepsy, encodes EFHC1, a protein with three DM10 domains and one EF-hand motif. We recently demonstrated that this molecule is a microtubule-associated protein (MAP) implicated in neuronal migration. Because some controversies persist about the precise localization in the CNS, we studied the neuroanatomical distribution of EFHC1 in mature and developing mouse brain. In the adult, low mRNA expression was detected in several brain structures such as cortex, striatum, hippocampus and cerebellum. At E16, EFHC1 mRNA was shown to be expressed in cortex and not only in cells lining ventricles. Using a purified polyclonal antibody, EFHC1 staining was observed in all cortical layers, in piriform cortex, in hippocampus and in Purkinje cells of cerebellum. In the cortex, the majority of EFHC1 positive cells correspond to neurons, however some glial cells were also stained. In agreement with a previous study, we demonstrated strong EFHC1 expression in cilia of ependymal cells lining cerebral ventricles. Moreover, at E16, the protein was observed at the borders of brain ventricles, in choroid plexus, but also, although to a lesser extent, in piriform and neocortex. In these latter structures, the pattern of expression seems to correspond to the extensions of the radial glia fibers as demonstrated by BLBP immunostaining. Finally, we confirmed that EFHC1 was also expressed and co-localized with the mitotic spindle of neural stem cells. These results confirm that EFHC1 is a protein with a likely low expression level in mouse brain but detectable both in adult and embryonic brain supporting our previous data and hypothesis that EFHC1 could play an important role during brain development. As discussed, this opens the door to a new conceptual approach viewing some idiopathic generalized epilepsies as developmental diseases instead of classical channelopathies.

EFHC1 interacts with microtubules to regulate cell division and cortical development.

Mutations in the EFHC1 gene are linked to juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic generalized epilepsies. JME is associated with subtle alterations of cortical and subcortical architecture, but the underlying pathological mechanism remains unknown. We found that EFHC1 is a microtubule-associated protein involved in the regulation of cell division. In vitro, EFHC1 loss of function disrupted mitotic spindle organization, impaired M phase progression, induced microtubule bundling and increased apoptosis. EFHC1 impairment in the rat developing neocortex by ex vivo and in utero electroporation caused a marked disruption of radial migration. We found that this effect was a result of cortical progenitors failing to exit the cell cycle and defects in the radial glia scaffold organization and in the locomotion of postmitotic neurons. Therefore, we propose that EFHC1 is a regulator of cell division and neuronal migration during cortical development and that disruption of its functions leads to JME.

Flavonol tetraglycosides from fruits of Styphnolobium japonicum (Leguminosae) and the authentication of Fructus Sophorae and Flos Sophorae.

The dried fruits and seeds of Styphnolobium japonicum (L.) Schott (syn. Sophora japonica L.) are used in traditional Chinese medicine and known as Fructus Sophorae or Huai Jiao. The major flavonoids in these fruits and seeds were studied by LC-MS and other spectroscopic techniques to aid the chemical authentication of Fructus Sophorae. Among the flavonoids were two previously unreported kaempferol glycosides: kaempferol 3-O-beta-glucopyranosyl(1-->2)-beta-galactopyranoside-7-O-alpha-rhamnopyranoside and kaempferol 3-O-beta-xylopyranosyl(1-->3)-alpha-rhamnopyranosyl(1-->6)[beta-glucopyranosyl(1-->2)]-beta-glucopyranoside, the structures of which were determined by NMR. Two further tetraglycosides were identified for the first time in S. japonicum as kaempferol 3-O-beta-glucopyranosyl(1-->2)[alpha-rhamnopyranosyl(1-->6)]-beta-glucopyranoside-7-O-alpha-rhamnopyranoside and kaempferol 3-O-beta-glucopyranosyl(1-->2)[alpha-rhamnopyranosyl(1-->6)]-beta-galactopyranoside-7-O-alpha-rhamnopyranoside; the latter was the main flavonoid in mature seeds. The chromatographic profiles of 27 recorded flavonoids were relatively consistent among fruits of similar ages collected from five trees of S. japonicum, and those of maturing unripe and ripe fruits were similar to a market sample of Fructus Sophorae, and thus provide useful markers for authentication of this herbal ingredient. The flower buds (Huai Mi) and flowers (Huai Hua) of S. japonicum (collectively Flos Sophorae) contained rutin as the main flavonoid and lacked the flavone glycosides that were present in flower buds and flowers of Sophora flavescens Ait., reported to be occasional substitutes for Flos Sophorae. The single major flavonoid in fruits of S. flavescens was determined as 3'-hydroxydaidzein.

Botanical nomenclature in pharmacovigilance and a recommendation for standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.

EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus.

A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we expressed EGFP-tagged protein in various cell lines. In interphase cells, the fusion protein was present in the cytoplasm and in the nucleus with specific accumulation at the centrosome. During mitosis EGFP-EFHC1 colocalized with the mitotic spindle, especially at spindle poles and with the midbody during cytokinesis. Using a specific antibody, we demonstrated the same distribution of the endogenous protein. Deletion analyses revealed that the N-terminal region of EFHC1 is crucial for the association with the mitotic spindle and the midbody. Our results suggest that EFHC1 could play an important role during cell division.

Botanical Nomenclature in Pharmacovigilance and a Recommendation for Standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.