Standardization of Andrographis paniculata, Mitracarpus scaber and Nauclea latifolia Herbal Preparations as per European and Nigerian Drug Regulations.

Background: Herbal drug standardization (HDS) is multidisciplinary with botany and chemistry working together to facilitate decisions on production of herbal medicines. The common reasons for HDS are: i) it creates the need for establishing botanical identity; ii) it is necessary for establishing dosage and iii) it facilitates industrial production and good manufacturing practice (GMP). Aims: To outline the strategies being used to standardize Conavir, Niprd-AM1 and Niprifan and to show that HDS is the ideal strategy for herbal drug development (HDD) from traditional medicines (TMs). Methodology: Relevant data on: i) the regulatory requirements of Europe’s Medicines Evaluation Agency (EMEA) and Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) and ii) on Andrographis paniculata (AP), Mitracarpus scaber (MS) and Nauclea latifolia (NL) were reviewed. Crude herbal drugs (CHDs) from aerial parts each of AP and MS and from roots of NL and the active crude extracts (ACEs) derived from them were studied using standard botanical, phytochemical and physicochemical techniques with the aim of standardizing them for production. The ACEs from AP (Conavir) and from NL (Niprd-AM1) were dry water extracts. The ACE from MS (Niprifan) was a dry ethylacetate extract. Results: The regulatory provisions of NAFDAC for herbal preparations were broadly similar to those of EMEA but the latter proved more explicit in many respects. Furthermore, the results on the CHDs and ACEs adequately meet the requirements of the two agencies. Conclusions: The results here provided and those reported elsewhere collectively furnish the data needed for drawing-up the registration dossiers of AP/Conavir, NL/Niprd- AM1 and MS/Niprifan as per EMEA and NAFDAC requirements. But for purposes of further work, it is needful for the GC-MS studies to be amplified and combined with others, so as to facilitate identification of suitable markers and pave the way for studies requiring bioassays.

A Comparison of the Performances on the MMSE, HDS-R, and MoCA According to the CDR Sum of Boxes in Amnestic Mild Cognitive Impairment and Vascular Mild Cognitive Impairment

BACKGROUND: O'Bryant et al. (2008) argued that the CDR Sum of Boxes (CDR-SB) can be used to distinguish MCI from very early dementia in patients with CDR-GS of 0.5. They reported that the optimal CDR-SB cut-off score was 2.5. The present study was conducted to examine whether the subgroups classified with CDR-SB scores showed the corresponding group differences on the cognitive tests. METHODS: The subjects were 45 amnestic multi-domain MCI (amMCI) and 53 vascular MCI (VaMCI) with CDR-GS of 0.5. Each patient group was classified into "mild (0.5-2.0)" and "severe (2.5-4.0)" subgroups based on the CDR-SB. As the result, 4 groups were formed such as mild amMCI (n=23), severe amMCI (n=22), mild VaMCI (n=29), and severe VaMCI (n=24). The subjects were given the MMSE, HDS-R, and MoCA. The MANCOVA was conducted separately for each test with a Bonferroni correction for multiple comparisons. RESULTS: Severe groups of both amMCI and VaMCI showed significantly lower performances than two mild groups in MMSE, HDS-R, and MoCA. It was found that "serial 100-7" was a good item to discriminate between the mild and severe groups in both amMCI and VaMCI. Items measuring "orientation" or "naming" showed significant subgroup differences in the amMCI, whereas items related to "memory," "visuospatial construction," or "frontal/executive function" showed significant subgroup differences in the VaMCI. CONCLUSION: These results showed that there were significant differences in cognitive functions between the two subgroups with CDR-GS of 0.5. The results about the items discriminating between subgroups in amMCI and VaMCI were consistent with the previous findings about the progression of cognitive impairments in AD and VaD. Therefore, these results support the use of CDR-SB as a guideline for distinguishing MCI from early dementia.

<b>The Effectiveness of Hangebyakujutsutemmato </b><b>for Alzheimer's Type Dementia </b> / 日本東洋医学雑誌

Dementia of the Alzheimer's type, in which cognitive impairment slowly progresses, accounts for more than half of dementia cases. Symptoms develop slowly and worsen over time, and there is no cure for Alzheimer's type dementia. We conducted a study on the efficacy of hangebyakujutsutemmato for cognitive impairment in dementia of the Alzheimer's type. Seventy-two patients with Alzheimer's type dementia were enrolled in our study. Hasegawa dementia scale-revised (HDS-R) was implemented for all patients, for whom hangebyakujutsutemmato medication was started at the initial visit. After 4-weeks' treatment the HDS-R was implemented again. Sixty-four patients were assessable and 8 patients dropped out from the study. In these 64 patients, mean age ± standard deviation was 79.9 ± 6.0, and 33 patients were male, and 31 patients were female. After 4 weeks of hangebyakujutsutemmato treatment, HDS-R scores were increased significantly compared with baseline (from 15.5 ± 5.2 to 16.9 ± 6.2, p < 0.01). In taking histories from families, clinical presentation was shown to have improved in 13 patients (20.3%). To our knowledge, this is the first report demonstrating that hangebyakujutsutemmato is effective for patients with dementia of the Alzheimer's type. In conclusion, hangebyakujutsutemmato is a useful option for the treatment of cognitive impairment in Alzheimer's type dementia.

Cloning and function analyses of HDS gene from Artemisia annua / 中草药

Objective To obtain the indispensable key enzyme-hydroxide methyl enylamino 4-cyclodiphosphate synthase (HDS) gene involved in the MEP pathway cloned from Artemisia annua and conduct bioinformatic and functional complementation analysis. Methods To perform multiple sequence alignment for the nucleotide acid sequence of the other reported seed plants' HDS gene, to select conservative areas for designing degenerate primers, and to gain the aim gene from A. annua through homologous expanding and cDNA bottom speedily expanding technique. To perform sequence alignment using BLAST, to identify open reading frame (ORF) using ORF Finder, and to construct phylogenetic tree using neighbor joining (NJ) ways in MEGA3.0. Results The obtained HDS cDNA sequence was 2 324 bp containing a 1 854 bp ORF and encoding a 617-amino acid protein. Bioinformatic analysis showed that AaHDS was homologous with HDS derived from other seed plant species. Functional complementation analysis indicated that AaHDS could make up the short HDS function of mutant Escherichia coli MG1655 araHDS. It could make the mutant get back to upgrowth, which showed AaHDS had typical HDS gene function. Conclusion The cloning HDS gene from A. annua for the first time provides a good basis for further study on the metabolization project of artemisinin.

Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p. R186C in the HSD11B2 gene / Síndrome de excesso aparente de mineralocorticóide em um menino brasileiro causada pela mutação p. R186C em homozigose no gene HSD11B2

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.

A síndrome de excesso aparente de mineralocorticóide (AME) é uma doença autossômica recessiva rara devido à deficiência da enzima 11β-hidroxiesterσide desidrogenase tipo 2 (11beta-HSD2). A enzima 11beta-HSD2 metaboliza o cortisol ativo a cortisona. As mutações no gene HSD11B2, que codifica a enzima, afetam sua atividade levando a um excesso de cortisol, que terá acesso inapropriado ao receptor de mineralocorticóide, competindo com a ligação da aldosterona. O gene HDS11B2 humano está localizado no cromossomo 16q22 e é formado por 5 éxons que codificam uma proteína de 405 aminoácidos. Este relato apresenta os estudos clínicos e moleculares de um paciente brasileiro do sexo masculino que nasceu prematuro depois de uma gestação sob oligodrâmnio. Recebeu o diagnóstico de AME com 26 meses de idade. Seus pais são primos em segundo grau. A caracterização molecular do gene HSD11B2 revelou a mutação p.R186C em homozigose. O paciente descrito é o segundo caso relatado de brasileiro com mutação no gene HSD11B2.

COMPORTAMIENTO DEL CATALIZADOR CoMo/[1]-Al2O3 MODIFICADO CON BORO Y POTASIO EN LAS REACCIONES SIMULTÁNEAS DE HIDROGENACIÓN DE OLEFINAS E HIDRODESULFURACIÓN DE 2-METILTIOFENO / THE PERFORMANCE OF CoMo/[1]-Al2O3 CATALYST MODIFIED WITH BORON AND POTASSIUM IN SIMULTANEUOUS REACTIONS OF OLEFINS HYDROGENATION AND 2-METHYLTHIOPHENE HYDRODESULFURIZATION / COMPORTAMENTO DO CATALISADOR CoMo/[1]-Al2O3 MODIFICADO COM BORO E POTÁSSIO NAS REAÇÕES SIMULTÂNEAS DO HIDROGENAÇÃO DE OLEFINAS E HIDRODESULFONAÇÃO DO 2 METILTIOFENO

Las características ácido-base de la [1]-alúmina, soporte de catalizadores sulfurados CoMo/[1]-Al2O3, fueron modificadas por la adición de boro (2, 3, 5, y 8% B2O3) y potasio (1, 3 y 5%K). Estos catalizadores fueron ensayados en reacciones simultáneas de hidrogenación (HID) de olefinas (2,4,4 trimetil-1-penteno y 2,4,4 trimetil- 2-penteno; 3:1) e hidrodesulfuración (HDS) de 2-metiltiofeno, simulando el hidrotratamiento (HDT) de una nafta de craqueo o de FCC (Fluidized Catalytic Cracking). Los resultados mostraron que aunque los cambios inducidos en las características ácido-base del soporte de alúmina disminuyeron la actividad para la HID y la HDS de los catalizadores, también dieron lugar a cambios apreciables en la selectividad hacia la HDS de tiofenos relativa a la HID de olefinas, lo que los convierte en buenos candidatos para el HDT de la nafta de FCC. Por otro lado, el craqueo, la alquilación y la isomerización de metilos se favorecieron cuando se hicieron las modificaciones con B, lo mismo que la migración del doble enlace de las olefinas ramificadas cuando se hizo la modificación con K. Los resultados de este trabajo permiten concluir que la actividad y selectividad del catalizador CoMo/[1]-Al2O3 para la HDS de la nafta de FCC pueden ser controladas por una adecuada modificación de las propiedades ácido-base del soporte de alúmina mediante la adición de pequeñas cantidades de B y de K.

The acid-base characteristics of the [1]-alumina support of sulfide CoMo catalysts were modified by boron (2, 3, 5, y 8% B2O3) and potassium (1, 3 y 5% K) addition. The catalysts were tested in simultaneous olefins (2,4,4-trimethyl-1-pentene y 2,4,4 trimethyl-2-pentene) hydrogenation (HYD) and 2-methyl-thiophene hydrodesulfurization (HDS) reactions, simulating the hydrotreating (HDT) of FCC (Fluidized Catalytic Cracking) naphtha. Results show that acid-base changes induced by B and K addition lead to an activity decrease in both HYD and HDS reactions, but, by contrast, an interesting increase in selectivity toward HDS over olefins HYD was also observed. These characteristics make these modified catalysts good candidates to be used in the naphtha HDT process. On the other hand, addition of B promotes cracking and methyl isomerization reactions, while, modification with K favors the double bond migration in branched olefins. The results of this work allow us to conclude that the activity and selectivity of CoMo/[1]-alumina catalysts for the HDS of FCC naphtha can be controlled by a proper modification of the acid-base properties of the alumina support by the addition of small quantities of B and K.

As características ácido-base da [1]-alumina, suporte de catalisadores sulfurados CoMo/[1]-Al2O3, foram modificadas pela adição de boro (2, 3, 5 e 8% B203) e potássio (1, 3 e 5% K). Estes catalisadores foram ensaiados em reações simultâneas de hidrogenação (HID) de olefinas (2,4,4 trimetil- 1-penteno y 2,4,4 trimetil-2-penteno; 3:1) e hidrosulfuração (HDS) de 2-metiltiofeno, simulando o hidrotratamento (HDT) de uma nafta de craqueo ou de FCC (Fluidized Catalytic Cracking). Os resultados mostraram que embora as mudanças induzidas nas características ácido - base do suporte de alumina, diminuíram a atividade para a HIDe a HDS dos catalisadores, também deram lugar a mudanças apreciáveis na seletividade pela HDS de tiofenos relativa à HID de olefinas, o que os converte em bons candidatos para o HDT da nafta de FCC. Por outro lado, o craqueo, a alquilação e a isomerização de metilos foram favorecidos quando foram feitas as modificações com B, o mesmo que a migração do enlace duplo das olefinas ramificadas quando se fez amodificação com K. Os resultados deste trabalho permitem concluir que a atividade e seletividade do catalisador CoMo/[1]-Al2O3 para a HDS da nafta de FCC, pode ser controlada por uma adequada modificação das propriedades ácido-base do suporte de alumina perante a adição de pequenas quantidades de B e de K.

Reliability and Validity of the Korean Version of Revised form of Hasegawa Dementia Scale (K-HDS)

BACKGROUND: The revised version of the Hasegawa Dementia Scale (HDS-R) is a useful dementia screening tool with a test for frontal lobe function and is relatively less influenced by education level and linguistic ability. We developed a Korean version of HDS-R (K-HDS) by translating the HDS-R to screen dementia patients in the Korean elderly. METHODS: The basic structure of the HDS-R was preserved but some questions were modified for lingual and cultural difference. It was administrated along with the Korean version of the MMSE, Korean Dementia Screening Questionnaire, Short form Samsung Dementia Questionnaire and Clinical Dementia Rating (CDR) scales, to 151 patients (55 Alzheimer's disease, 73 vascular dementia, 23 others) with mild to moderate dementia and to 225 elderly control subjects. To screen dementia, the optimal cut-off score was estimated by receiver operating characteristic (ROC) curve analysis. By comparing the Area Under the Curve, the diagnostic efficiency of K-HDS was compared with that of K-MMSE. RESULTS: The K-HDS had good internal consistency (Crohnbach's alpha coefficient=0.66), inter-rater reliability (r=0.95), and test-retest reliability (r=0.92). K-HDS was well correlated with the K-MMSE (r=0.84) and CDR (r=-0.67), which confirms the validity of this test. The optimal cut-off score was different according to educational level. In patients with an educational level less than 10 years, the cut-off score was 20 with the sensitivity of 87.0% and the specificity of 83%. With an educational level of 10 years or more, the cut-off score was 22 with the sensitivity of 93.0% and the specificity of 89.6%. The overall diagnostic efficiency of K-HDS was superior to that of K-MMSE especially in patients with an educational level of less than 10 years. CONCLUSIONS: The K-HDS is a reliable, valid and useful tool to screen dementia in the Korean elderly.

Reliability and Validity of the Korean Version of Hasegawa Dementia Scale(HDS-K) as a Dementia Screening Instrument / 신경정신의학

OBJECTS: We developed the Korean version of Hasegawa Dementia Scale(HDS-K) by translating the revised Hasegawa Dementia Scale(HDS-R) which is known to be a useful brief screening instrument for dementia. MATERIALS AND METHODS: The translation was carried out keeping the basic structure of Revised Hasegawa Dementia Scale(HDS-R). HDS-K, along with MMSE-KC, SBT-K and CDR, were administered to 174 dementia patients and 160 elderly control subjects. Cronbach alpha coefficient, inter-rator reliability, and test-retest reliability of HDS-K were examined. The correlations of MMSE-KC, SBT-K and CDR with HDS-K were also examined to confirm the validity of HDS-K. Cut-off scores for dementia were estimated by Receiver Operator Characteristic(ROC) curve anslyses. By comparing Area Under Curve(AUC), the diagnostic efficiency of HDS-K was compared with those of MMSE-KC and SBT-K. RESULTS: 1) HDS-K was found to have significantly high internal consistency(Cronbach alpha coefficient=0.948, <0.01), inter-rater reliability(Pearson correlation coefficient=0.999, <0.01) and test-retest reliability(Pearson correlation coefficient=0.848, <0.01). 2) All the correlations of HDS-K with MMSE-KC, SBT-K and CDR were significant indicating that HDS-K has good concurrent validity. Its optimal cut-off point for dementia was estimated as 15/16, where the sensitivity and specificity were 0.950 and 0.902, respectively. 3) The ROC curve analysis indicated that the diagnostic efficiency of HDS-K(AUC=0.972) was comparable with MMSE-KC(AUC=0.951) and SBT-K(AUC=0.963). CONCLUSION: We conclude that HDS-K is a reliable, valid, and useful screening instrument for dementia.

Effect of TEAS(Transcutaneous Electrical Acupuncture Point Stimulation) on Intellect and Daily Activity of the Aged / 全日本鍼灸学会雑誌

We investigated whether TEAS affected intellect in the elderly, prevented the decline of daily activity and/or improved HDS-R and elderly activity valuation scale in 93 aged patients over 70.<BR>As a result, HDS-R and the elderly activity valuation scale increased after 8 weeks, in the physical exercise group that also received TEAS treatment, indicating a tendency to improve. Improved intellect was measured by asking subject to guess the time and date, recollect some words, and remember five items in HDS-R. All items on the elderly activity valuation scale were improved except for hearing and appetite. Many patients showed increased scores in combination with TEAS. Before treatment, patients in both groups were divided into 4 subgroups by HDS-R score and change in HDS-R was investigated after treatment for 8 weeks. Those scoring 16 points or more on the initial test tended to show an increased score in both groups, those showing 11-15 points initially demonstrated an increased score only in exercise in the combined group, and those showing 10 points or less did not demonstrate any change in either group.<BR>Based on these results, physical therapy combined with TEAS appeared to accelerate daily activity and promote intellect and cognition in the elderly.

Activities of Hepatic Antioxidant Enzymes in Rats during 14 Days of Head-down Suspension as a Model of Simulated Weightlessness

Cells and tissues of human and animal are protected against free radicals by several complex mechanisms including the action of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase. There had been a few reports that simulated or actual weightlessness induced the decrease in activity of antioxidant enzymes and the increase in lipid peroxidation, The purpose of this study was to observe the time-course variation of antioxidant enzymes activities in rats during 14 days of head-down suspension(HDS) at -45 degrees as a model of simulated weightlessness. During HDS, the hepatic activity of SOD significantly decreased (p<0.05) at 3 day of HDS and then maintained a lower value compared to control horizontal position, GSH-Px activity also significantly decreased (p<0.05) at 3 and 7 day of HDS, thereafter showed a slight increasing trend to control horizontal value. The activity of hepatic catalase increased during HDS and the value at the end of HDS showed significant increase (p<0.05). From these results, there is a possibility that weightlessness induce the increase of oxygen free radicals according to the decrease of some antioxidant enzyme activities. The main scavenger to oxygen free radicals is operated via catalase system in rats during HDS. Therefore, we suggest that it is necessary to administrate the antioxidants for protection of the body against oxygen free radicals during first 1 week after exposure of weightlessness, at least.