To encourage development of new drugs from botanical sources, the U. S Food and Drug Administration (FDA) has published a draft Guidance for Industry: Botanical Drug Products (www.fda.gov/cder/guidance/1221.dft.pdf) in August of 2000.
The Guidance stipulates that for herbal preparations with substantial marketing history, past human experiences may be taken into consideration for safety assessment. In contrast with development of pure chemical drugs, clinical studies on herbal medicines can thus be initialed with less extensive lesting of non-clinical toxicity. However, most of the historical human experlences are not well documentad and often of poor quality data. In such cases, animal toxicity and toxicology studies may still be required for many botanical preparations, especially to support large scale or long term clinical trials. In this presentation, conventional non-clinical requirements for approval of pure chemical drugs will be reviewed briefly and how such requirements may be modified in scale/timing and applied to the development of botanical new drugs will be discussed.

In this paper, we report three cases of orbital rhabdomyosarcoma in different age groups with different histopathologic types. Case 1 is a 10-year old Malay boy who presented with painless proptosis of the left eye. Magnetic resonance imaging (MRI) showed soft tissue mass arising from the lateral rectus muscle. Tissue biopsy revealed rhabdomyosarcoma of embryonal type. Case 2 is a 32-year old Malay man who presented with a progressive left eye proptosis associated with pain and redness. Computed Tomography (CT) scan showed a retrobulbar mass extending medially in the left orbit. Meanwhile, biopsy showed rhabdomyosarcoma of pleomorphic type. Case 3 is a 67-year old Malay woman who presented with proptosis and fungating growth of left orbital region, epistaxis and nasal blockage. CT scan revealed an ill-defi ned mass fi lling up the left orbital cavity. Biopsy showed rhabdomyosarcoma of alveolar type. Rhabdomyosarcoma is the most common in childhood but it should be considered as a differential diagnosis of orbital tumours irrespective of age.

Introduction: Persons with disabilities (PWD) are susceptible to malnutrition. Caregivers or teachers in rehabilitation centres may not be adequately trained in nutrition management of PWD. The aims of this study were (i) to assess the nutrition knowledge, attitude and practice among teachers in community-based rehabilitation centres for PWD; and (ii) to evaluate changes in the nutrition knowledge and attitude of the teachers before and after exposure to a training workshop on nutrition management for PWD. Methods: A cross-sectional survey was conducted using a guided self-administered Nutrition Knowledge, Attitude and Practice Questionnaire on Persons with Disabilities (KAP-nOKU), among a convenience sample of 210 teachers. Forty-five of them further participated in a nutrition training workshop and completed the post-test evaluation on knowledge and attitude of the same measures. Results: At baseline, the teachers’ average knowledge, attitude and practice scores were 13.80±3.73 for knowledge (below 50th percentile); 51.49±4.08 for attitude (above 75th percentile); and 48.08±3.61 for practice (between 50th and 75th percentile). There was significant positive correlations between knowledge and attitude (r=0.343, p<0.05), as well as between attitude and practice (r=0.147, p<0.05). After exposure to a 3-day nutrition workshop, significant improvements in the teachers’ knowledge and attitude were observed, whereby teachers’ knowledge score increased from 14.20±3.80 to 25.38±2.36 and from 51.16±3.97 to 55.20±4.41 for attitude (p<0.001). Conclusion: Nutrition intervention was associated with improvement in short term knowledge and attitude of the teachers. Sustainable interventional strategies are needed to enhance the nutrition knowledge and skills of teachers of PWD.

China ; epidemiology ; Humans ; Venous Thromboembolism ; diagnosis ; drug therapy ; epidemiology

Ovitrap surveillance was initiated for eight continuous weeks to determine the distribution and abundance of Aedes sp. mosquitoes in the University of Malaya campus, Kuala Lumpur, and the impact of meteorological conditions on the Aedes populations. Two study areas within the campus were selected: Varsity Lake and Seventh Residential College. The abundance of Aedes populations in Varsity Lake was indicated by ovitrap index (OI) which ranged from 60.00% - 90.00%. The mean number of larvae per ovitrap of Aedes albopictus in Varsity Lake ranged from 11.23 +/- 2.42 - 43.80 +/- 6.22. On the other hand, the outdoor OI for Seventh Residential College ranged from 73.33% - 93.33%, respectively, while the mean number larvae per ovitrap for this area ranged from 19.33 +/- 4.55 - 35.27 +/- 5.46, respectively. In addition, the indoor OI of Seventh Residential College ranged from 0.00% - 30.00%, while the mean number of larvae per ovitrap for Ae. albopictus ranged from 0 - 5.90 +/- 3.55. There was no significant difference (p > 0.05) of Ae. albopictus population between Varsity Lake and Seventh Residential College. The studies showed a correlation between OI and mean number of larvae per ovitrap for outdoor Ae. albopictus populations in Varsity Lake and Seventh Residential College (r = 0.794). There was also a correlation between the mean larvae number per ovitrap of Ae. albopictus obtained from eight weeks indoor ovitrap surveillance in Seventh Residential College with rainfall (r = 0.584). However, there was no correlation between the mean larvae number per ovitrap of Ae. albopictus in both study areas with temperature and relative humidity. Aedes aegypti mosquitoes were found neither indoor nor outdoor in both study areas. This study indicated that the principal dengue vector in the university campus was most likely Ae. albopictus.
College ; Seventh ; Lake ; Aedes ; seconds

OBJECTIVE：To study the effects o f CYP2C9*3 gene polymorphism on therapeutic efficacy of benzbromarone in lowering uric acid and its hepatotoxicity. METHODS ：A retrospective study was conducted to analyze the relevant clinical indicators and genotypes of 196 gout patients who received benzbromarone and CYP2C9*3 gene polymorphism test in Wuhan third hospital from Jan. 2018 to Sept. 2019. RESULTS ：Among 196 patients，179，15 and 2 patients with CYP2C9*3 genotypes * 1/*1， *1/*3 and * 3/*3 genotypes were found ，respectively，and the distribution of each genotype was in line with Hardy-Weinberg balance（P＞0.05）. Before treatment ，there were no significant differences in the levels of UA ，Scr，ALT，AST and CRP between *1/*1 genotype and * 1/*3+*3/*3 genotype（P＞0.05）. After 4 weeks of treatment ，the UA ，Scr，CRP levels of patients with * 1/*1 genotype as well as the UA and CRP levels of patients with * 1/*3+*3/*3 genotype were significantly reduced ，the UA level of patients with * 1/*1 genotype was significantly lower than that of patients with * 1/*3+*3/*3 genotype（P＜0.05 or P＜0.01）. The ALT and AST levels had no obvious changes in patients with different genotype before and after treatment ，and they were in the normal range. No serious abnormal liver function was observed during the treatment. CONCLUSIONS ：Therapeutic efficacy of benzbromarone in lowering uric acid in gout patients with CYP2C9*3 genotypes * 1/*1 genotype is better than that of * 1/*3 and * 3/*3 genotypes. However ，the gene polymorphism may be not associated with its hepatotoxicity.

OBJECTIVETo investigate the effects of artificial ligand of peroxisome proliferators activated receptors (PPARs), rosiglitazone (RGZ) and all trans-retinoic acid (ATRA) on human myeloma cell line growth in vitro and in vivo.

METHODSU266 and RPMI 8226 cells were treated with different concentration of RGZ in the presence or absence of ATRA and the results were studied by 3H-TdR thymidine incorporation (for cells proliferation), Annexin V-PI staining and caspase-3 activity assay (for cells apoptosis), RT-PCR (for FLIP, XIAP and survivin mRNA expression), and tumor formation test in BALB/c nude mice.

RESULTSExposure to RGZ induced proliferation inhibition in a dose-dependent manner in both U266 (r = 0.991, P < 0.01) and RPMI 8226 cells (r = 0.961, P < 0.01). A combination of RGZ with ATRA could enhance the inhibition effect (P < 0.001 in U266, P < 0.01 in RPMI8226). 10 micromol/L of RGZ induced apoptosis of (9.8 +/- 1.7)% in U266 cells and (10.7 +/- 3.3)% in RPMI8226 cells, in a time and dose dependent manner and combined with ATRA intensified the apoptosis induction effects (P < 0.01 in both cell lines). The FLIP, XIAP and survivin mRNAs were expressed in both cell lines and their levels decreased significantly after cultured with RGZ. The addition of RGZ + ATRA in the culture further decreased the levels. Caspase-3 activity increased substantially with the increase of RGZ concentration and the addition of RGZ + ATRA in the culture medium showed similar synergism effect on caspase-3 activation (P < 0.01). The xenograft of U266 cells in BALB/c nude mice were inhibited by RGZ and so did more by the combination of RGZ and ATRA (P < 0.01).

CONCLUSIONThe down-regulation of FLIP, XIAP and Survivin induced by RGZ can activate caspase-3, whereby induced apoptosis and proliferation inhibition in myeloma cells. ATRA can enhance these effects of RGZ.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Multiple Myeloma ; metabolism ; pathology ; Signal Transduction ; drug effects ; Thiazolidinediones ; pharmacology ; Tretinoin ; pharmacology

OBJECTIVE: Angioplasty and Stenting of intracranial atherosclerotic lesions have a higher complication rate and a large proportion of this is attributable to side branch arterial occlusion from forceful displacement of the atheroma into the ostia or snowplowing effect. This can result in severe disabilities when it result in small infarcts involving eloquent areas in the posterior circulation or the motor tracts. MATERIALS AND METHODS: We present a series of 6 cases utilizing a new dual catheter technique for maintaining the patency of at-risk vessels during angioplasty and stenting. There are several methods previously described to help reduce the incidence of stroke but because they do not have a physical presence in the ostia to protect it, they are unable to guarantee the patency of the vessel. RESULTS: All 6 patients underwent angioplasty and stenting with the technique. The patients were assessed for complications with post-procedure magnetic resonance imaging and no complications were found. CONCLUSION: In this preliminary series, the dual catheter technique appears to safe and effective in preventing occlusion of the adjacent branch arteries. This technique may facilitate the use of the Wingspan stent in the treatment of intracranial atherosclerotic stenotic segments by reducing the risk of peri-procedural stroke.
Angioplasty* ; Arteries ; Catheters* ; Humans ; Incidence ; Magnetic Resonance Imaging ; Plaque, Atherosclerotic ; Stents* ; Stroke

BACKGROUND/OBJECTIVES: This study aimed to establish a mother and child cohort in the Chinese population, and investigate human breastmilk (HBM) composition and its relationship with maternal body mass index (BMI) and infant growth during the first 3 mon of life. SUBJECTS/METHODS: A total of 101 Chinese mother and infant pairs were included in this prospective cohort. Alterations in the milk macronutrients of Chinese mothers at 1 mon (T1), 2 mon (T2), and 3 mon (T3) lactation were analyzed. HBM fatty acid (FA) profiles were measured by gas chromatography (GC), and HBM proteomic profiling was achieved by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). RESULTS: During the first 3 mon of lactation (P < 0.05), significant decreases were determined in the levels of total energy, fat, protein, and osteopontin (OPN), as well as ratios of long-chain saturated FA (including C16:0, C22:0 and C24:0), monounsaturated FA (including C16:1), and n-6 poly unsaturated FA (PUFA) (including C20:3n-6 and C20:4n-6, and n-6-3). Conversely, butyrate, C6:0 and n-3 PUFA C18:3n-3 (α-linolenic acid, ALA) were significantly increased during the first 3 mon (P < 0.05). HBM proteomic analyses distinguished compositional protein differences over time (P = 0.001). Personalized motherinfant analyses demonstrated that HBM from high BMI mothers presented increased total energy, fat, protein and OPN, and increased content of n-6 PUFA (including C18:3n-6, C20:3n-6 and n-6-3 ratio) as compared with low BMI mothers (P < 0.05). Furthermore, BMI of the mothers positively correlated with the head circumference (HC) of infants as well as the specific n-6 PUFA C20:3n-6 over the 3 time points examined. Infant HC was negatively associated with C18:0. CONCLUSION This study provides additional evidence to the Chinese HBM database, and further knowledge of FA function. It also helps to establish future maternal strategies that support the healthy growth and development of Chinese infants.

BACKGROUND/OBJECTIVES: This study aimed to establish a mother and child cohort in the Chinese population, and investigate human breastmilk (HBM) composition and its relationship with maternal body mass index (BMI) and infant growth during the first 3 mon of life. SUBJECTS/METHODS: A total of 101 Chinese mother and infant pairs were included in this prospective cohort. Alterations in the milk macronutrients of Chinese mothers at 1 mon (T1), 2 mon (T2), and 3 mon (T3) lactation were analyzed. HBM fatty acid (FA) profiles were measured by gas chromatography (GC), and HBM proteomic profiling was achieved by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). RESULTS: During the first 3 mon of lactation (P < 0.05), significant decreases were determined in the levels of total energy, fat, protein, and osteopontin (OPN), as well as ratios of long-chain saturated FA (including C16:0, C22:0 and C24:0), monounsaturated FA (including C16:1), and n-6 poly unsaturated FA (PUFA) (including C20:3n-6 and C20:4n-6, and n-6-3). Conversely, butyrate, C6:0 and n-3 PUFA C18:3n-3 (α-linolenic acid, ALA) were significantly increased during the first 3 mon (P < 0.05). HBM proteomic analyses distinguished compositional protein differences over time (P = 0.001). Personalized motherinfant analyses demonstrated that HBM from high BMI mothers presented increased total energy, fat, protein and OPN, and increased content of n-6 PUFA (including C18:3n-6, C20:3n-6 and n-6-3 ratio) as compared with low BMI mothers (P < 0.05). Furthermore, BMI of the mothers positively correlated with the head circumference (HC) of infants as well as the specific n-6 PUFA C20:3n-6 over the 3 time points examined. Infant HC was negatively associated with C18:0. CONCLUSION This study provides additional evidence to the Chinese HBM database, and further knowledge of FA function. It also helps to establish future maternal strategies that support the healthy growth and development of Chinese infants.