Bioactive phenazines from an earwig-associated Streptomyces sp / 中国天然药物

Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.

Comparison of the efficacy of metronidazole and metronidazole plus probiotics capsule in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary hospital: A single blind randomized controlled trial / Philippine Journal of Obstetrics and Gynecology

BACKGROUND: Bacterial vaginosis (BV) is the most prevalent cause of symptomatic vaginitis. In the Philippines, prevalence of BV is at 28.16%. The mainstay for the treatment of BV is Metronidazole. Although antibiotic therapy has been shown to eliminate BV associated organisms, there is extremely high recurrence rate.OBJECTIVE: To compare the efficacy of metronidazole and metronidazole plus lactobacilli tablet in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary medical center.METHODOLOGY: The population included non-pregnant women ages 15 t0 44 years old, with bacterial vaginosis diagnosed by Amsel's criteria and Nugent's scoring. The participants were randomly assigned to their treatment group, one is Metronidazole only and other received Metronidazole plus Lactobacillus tablet. All participants followed up on day 8,15,22 and 56 from initiation of treatment resolution or persistence of symptoms and collection of vaginal specimen for gram stain and inquire on adverse effects.RESULTS: On day 8 treatment, there were significantly more participant in the metronidazole plus probiotic arm with an estimated lactobacilli count of more than 30/hpf as comapred to metronidazole alone. On day 15 post treatment, there was no statistically significant difference with the estimated Gardnerella vaginalis count, lactobacilli count, presence or absence of malodorous vaginal discharge between the metronidazole plus probiotic and the metronidazole alone arm. With metronidazole plus probiotic group, the proportion of women with less than 30 per hpf Gardnella vaginalis count and absent foul smelling vaginal discharge were accounted among 100% of the participants from day 8 to 56 post treatment. The early reduction in the causative agent and symptoms can be attributed to an increase in the estimated lactobacilli count sustained until 56 days post treatment metronidazole plus probiotic. However, from day 15 to 22 and 56 post- treatment, the proportion of participants who had a nugent's score of less than 4 were greater for both the metronidazole plus probiotic (100%) and metronidazole alone (95%) arm, when compared to day 8 post-treatment. This finding for the metronidazole plus probiotic group is due to sustained reduction in the Gardnella vaginalis count and increase in lactobacilli counts. Potentially , the metronidazole plus probiotic treatment was found to be more favorable in sustaining the normal flora and probiotic can be used as an adjunct may enhance the efficacy of metronidazole in the treatment of BV.CONCLUSION: Metronidazole plus probiotic and metronidazole only treatment are comparable in treating bacterial vaginosis. In terms of restoring and maintaining the normal flora, metronidazole plus probiotic appears to be more significantly efficacious. Probiotic in the form of lactobacilli is a promising adjunct to enhance the efficacy of metronidazole in the treatment of bacterial vaginosis.

Comparison of the efficacy of metronidazole and metronidazole plus probiotics capsule in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary hospital: A single blind randomized controlled trial / Philippine Journal of Obstetrics and Gynecology

BACKGROUND: Bacterial vaginosis (BV) is the most prevalent cause of symptomatic vaginitis. In the Philippines, prevalence of BV is at 28.16%. The mainstay for the treatment of BV is Metronidazole. Although antibiotic therapy has been shown to eliminate BV associated organisms, there is extremely high recurrence rate.OBJECTIVE: To compare the efficacy of metronidazole and metronidazole plus lactobacilli tablet in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary medical center.METHODOLOGY: The population included non-pregnant women ages 15 t0 44 years old, with bacterial vaginosis diagnosed by Amsel's criteria and Nugent's scoring. The participants were randomly assigned to their treatment group, one is Metronidazole only and other received Metronidazole plus Lactobacillus tablet. All participants followed up on day 8,15,22 and 56 from initiation of treatment resolution or persistence of symptoms and collection of vaginal specimen for gram stain and inquire on adverse effects.RESULTS: On day 8 treatment, there were significantly more participant in the metronidazole plus probiotic arm with an estimated lactobacilli count of more than 30/hpf as comapred to metronidazole alone. On day 15 post treatment, there was no statistically significant difference with the estimated Gardnerella vaginalis count, lactobacilli count, presence or absence of malodorous vaginal discharge between the metronidazole plus probiotic and the metronidazole alone arm. With metronidazole plus probiotic group, the proportion of women with less than 30 per hpf Gardnella vaginalis count and absent foul smelling vaginal discharge were accounted among 100% of the participants from day 8 to 56 post treatment. The early reduction in the causative agent and symptoms can be attributed to an increase in the estimated lactobacilli count sustained until 56 days post treatment metronidazole plus probiotic. However, from day 15 to 22 and 56 post- treatment, the proportion of participants who had a nugent's score of less than 4 were greater for both the metronidazole plus probiotic (100%) and metronidazole alone (95%) arm, when compared to day 8 post-treatment. This finding for the metronidazole plus probiotic group is due to sustained reduction in the Gardnella vaginalis count and increase in lactobacilli counts. Potentially , the metronidazole plus probiotic treatment was found to be more favorable in sustaining the normal flora and probiotic can be used as an adjunct may enhance the efficacy of metronidazole in the treatment of BV.CONCLUSION: Metronidazole plus probiotic and metronidazole only treatment are comparable in treating bacterial vaginosis. In terms of restoring and maintaining the normal flora, metronidazole plus probiotic appears to be more significantly efficacious. Probiotic in the form of lactobacilli is a promising adjunct to enhance the efficacy of metronidazole in the treatment of bacterial vaginosis.

Potential of Microbispora sp. V2 as biocontrol agent against Sclerotium rolfsii, the causative agent of southern blight of Zea mays L (Baby corn)–in vitro studies.

The study was undertaken with the aim of exploring novel and beneficial agro activities of rare actinomycetes like Microbispora sp. V2. The antagonistic activity of Microbispora sp. V2 was evaluated as a biocontrol agents against Sclerotium rolfsii, a soil-borne fungal plant pathogen. The methodology performed for evaluation of biocontrol agent was in vitro evaluation assay which comprised of three tests viz., cellophane overlay technique, seed germination test and Thiram (fungicide) tolerance of Microbispora sp. V2. The isolate was found to inhibit the fungal pathogen Sclerotium rolfsii to 91.43% in cellophane assay. In seed germination assay, Microbispora sp. V2 treated seeds resulted in 25.75% increased germination efficiency, as compared to seeds infected by Sclerotium rolfsii. The isolate Microbispora sp. V2 could tolerate 1000 µg mL-1 of Thiram (fungicide). The in vitro assay studies proved that Microbispora sp. V2 can be used as antifungal antagonist and thus posses’ great potential as biocontrol agent against southern blight caused by Sclerotium rolfsii in Zea mays L (Baby corn) which causes large economical losses.

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

Estudo bacteriológico do lavado broncoalveolar na gestão de antibióticos na pneumonia associada à ventilação mecânica de pacientes em unidades de terapia intensiva cirúrgica / Bacteriological study of bronchoalveolar lavage in the antibiotic management of suspected ventilator-associated pneumonia of patients in surgical intensive care units

OBJETIVO: determinar a correlação da coloração de Gram com o resultado final das culturas de LBA em pacientes cirúrgicos sob ventilação mecânica com PAV clínica. MÉTODOS: Estudo retrospectivo de 252 amostras de lavado broncoalveolar em pacientes com clínica de pneumonia associada à ventilação mecânica com trauma ou cuidados de pós-operatório. As amostras de coloração de Gram foram classificadas como cocos Gram-positivos e bacilos Gram-negativos, todos os outros resultados foram excluídos. Culturas de lavado broncoalveolar foram comparadas aos resultados da coloração de Gram. RESULTADOS: A correlação entre a coloração de Gram e a cultura do lavado broncoalveolar apresentou índice kappa de 0,27. A sensibilidade da coloração de Gram foi 53,9% e a especificidade de 80,6%. Considerando a identificação de cocos Gram-positivos comparada com os outros resultados (negativos e bacilos Gram-negativos), o valor preditivo negativo foi 94,8%. Na avaliação de bacilos Gram-negativos comparada com os outros resultados (negativos e cocos Gram-positivos), a sensibilidade foi 27,1% e a especificidade foi 95,4%. CONCLUSÃO: O valor preditivo negativo para cocos Gram-positivos parece ser aceitável, mas a sensibilidade da coloração de Gram na etiologia de pneumonia associada à ventilação mecânica não permite prever qual é o micro-organismo antes da cultura.

OBJECTIVE: To determine the correlation of Gram staining with the culture of bronchoalveolar lavage in patients with clinical features of ventilator-associated pneumonia from two adult trauma and surgical intensive care units. METHODS: We conducted a retrospective study of 252 samples of bronchoalveolar lavage from patients with clinical ventilator-associated pneumonia in trauma or surgical postoperative care. Gram staining samples were classified as Gram-positive cocci and Gram-negative bacilli, all other results being excluded. Cultures from bronchoalveolar lavage were compared with Gram staining results. RESULTS: The correlation between Gram staining and culture from the bronchoalveolar lavage showed a kappa index of 0.27. The sensitivity of Gram staining was 53.9% and the specificity, 80.6%. Considering the identification of Gram-positive cocci against other results (negative and Gram-negative bacilli), the negative predictive value was 94.8%. The evaluation of Gram-negative bacilli against other results (negative and Gram-positive cocci) rendered a sensitivity of 27.1% and a specificity of 95.4%. CONCLUSION: It appears that the negative predictive value for Gram-positive cocci is acceptable, but the sensitivity of Gram staining in the etiology of ventilator-associated pneumonia was not able to identify the microorganism before culture.

Análisis de la monitorización de cinco indicadores de calidad del hemocultivo en un hospital universitario en Chile 2009-2011 / Quality indicators for blood culture: three years of monitoring at a university hospital in Chile

Blood culture is considered the "gold standard" for the diagnosis of bacteremia, critical condition with high morbidity and mortality. Because of its importance, it is estimated that the blood culture is a critical test that requires close monitoring on the quality with which the process is performed. The objective of this work is to show the results of the monitoring carried out during the past three years, of 5 quality indicators of blood cultures in the laboratory of the Hospital Clínico de la Pontificia Universidad Católica de Chile, considering pre-analytical, analytical and post-analytical aspects. In the 3 years monitored the mean contamination was 0,7%, 46% of adult bottles had adequate volume, match between Gram stain with final identification was 99.4%, 100% of correct participations were achieved in surveys of external quality control and Gram staining notification before 1 hour was 88.7%. With regard to proposed aims, in 2011 the laboratory complies with all, except the percentage of bottles with appropriate volume of blood inoculated. This indicator is very low and should be corrected as soon as possible since it is known that it is an important condition for optimum performance of blood cultures.

El hemocultivo es el "estándar de oro" para el diagnóstico de bacteriemia, condición grave de alta morbi-mortalidad. Por esto, se estima que el hemocultivo es un examen crítico, que requiere monitorización de su calidad. El objetivo de este trabajo es mostrar los resultados de la monitorización de 3 años de 5 indicadores de calidad del hemocultivo implementados en nuestro hospital. El porcentaje promedio de contaminación de las botellas para hemocultivo fue 0,7%, el porcentaje de botellas de adultos con volumen adecuado fue 46%, la concordancia de la tinción de Gram con la identificación final correspondió a 99,4%, el 100% de las participaciones en encuestas de control de calidad externo fueron correctas y 88,7% de los avisos de valores de alerta de la tinción de Gram fueron realizados antes de 1 hora. En el año 2011 se cumplió con las metas propuestas por el laboratorio para todos los indicadores, excepto con el porcentaje de botellas con volumen apropiado de sangre. Este último, se encuentra muy por debajo de la meta y debe ser mejorado a la brevedad, ya que el volumen de sangre cultivada es el factor más importante para obtener un rendimiento óptimo del hemocultivo.

Espiroquetosis intestinal humana: serie clínica y revisión de la literatura / Human intestinal spirochetosis: clinical series and literature review

Introduction: Human intestinal spirochetosis (HIE) is defined as colonization by spirochetes of the large intestine. Is associated with chronic diarrhea. The incidence and prevalence ranges from 0.4% to 12%. Objective: To determine the prevalence of HIE in the Salvador's Hospital, between 2003 and 2008 in patients with a history of chronic diarrhea and without abnormalities in colonoscopy, in 2 separate groups: patients with and without a history of HIV infection. Material and Methods: Retrospective morphology evaluation of the large bowel endoscopic biopsies to the selected groups. Results: We reviewed 115 biopsies, 98 were from HIV-negative and 17 HIV from positive patients. Two cases of intestinal spirochetosis were detected, both HIV negative, with a prevalence of 1.7%. Comment: The prevalence of HIE is similar to that reported in Western countries. Population studies are needed to determine the real epidemiological impact in our environment.

Introducción: La espiroquetosis intestinal humana (EIH) se define como la colonización del intestino grueso por espiroquetas. Se asocia a diarrea crónica. Su incidencia y prevalencia van desde 0,4 a 12% Objetivo: Determinar la prevalencia de EIH en el Hospital Del Salvador, de Santiago, Chile, entre los años 2003 y 2008, en pacientes con antecedentes clínicos de diarrea crónica y colonoscopia sin hallazgos patológicos, separados en dos grupos: pacientes con y sin antecedentes de infección por VIH. Material y Método: Evaluación morfológica retrospectiva de las biopsias endoscópicas de intestino grueso de los grupos seleccionados. Resultados: Se revisaron 115 biopsias, 98 correspondieron a pacientes sin infección por VIH y 17 a pacientes seropositivos para VIH. Se detectaron dos casos de espiroquetosis intestinal, ambos en pacientes sin infección por VIH, con una prevalencia de 1,7 %. Comentario: La prevalencia de EIH es similar a la publicada en países occidentales. Se requieren estudios poblacionales para determinar el real impacto epidemiológico en nuestro medio.

Expression of phenazine biosynthetic genes during the arbuscular mycorrhizal symbiosis of Glomus intraradices

To explore the molecular mechanisms that prevail during the establishment of the arbuscular mycorrhiza symbiosis involving the genus Glomus, we transcriptionally analysed spores of Glomus intraradices BE3 during early hyphal growth. Among 458 transcripts initially identified as being expressed at presymbiotic stages, 20% of sequences had homology to previously characterized eukaryotic genes, 30% were homologous to fungal coding sequences, and 9% showed homology to previously characterized bacterial genes. Among them, GintPbr1a encodes a homolog to Phenazine Biosynthesis Regulator (Pbr) of Burkholderia cenocepacia, an pleiotropic regulatory protein that activates phenazine production through transcriptional activation of the protein D isochorismatase biosynthetic enzyme phzD (Ramos et al., 2010). Whereas GintPbr1a is expressed during the presymbiotic phase, the G. intraradices BE3 homolog of phzD (BGintphzD) is transcriptionally active at the time of the establishment of the arbuscular mycorrhizal symbiosis. DNA from isolated bacterial cultures found in spores of G. intraradices BE3 confirmed that both BGintPbr1a and BGintphzD are present in the genome of its potential endosymbionts. Taken together, our results indicate that spores of G. intraradices BE3 express bacterial phenazine biosynthetic genes at the onset of the fungal-plant symbiotic interaction.

Assessment of Treatment Outcome after Using Temporary Mandibular Advancement Devices in Obstructive Sleep Apnea Patients

50% Apnea-Hypopnea Index (AHI) reduction plus post-MAD AHI <10, and the non-response group was defined as <50% AHI reduction. The lateral cephalogram was analysed including SNA, SNB, UL, MPH, PAS, PASU, and PAST using V-ceph(TM) (Cybermed, USA).RESULTS: The responsers were 23 patients, and non-responsers were 5 patients. The AHI was significantly reduced with temporary MAD (8.08+/-7.93) compared with baseline (28.51+/-20.56) in the response group (n=23). No significant difference was observed between pre MAD and post MAD except SNB on cephalometric analysis. Among 11 patients successfully treated with the temporary device, 9 patients said that using permanent device brings better effect too.CONCLUSION: These results indicate that the Temporary MAD could not be the only effective tools on OSA but also be used to predict patient's reactivity about permanent appliance treatment. Further studies are warranted to evaluate the relations between temporary MAD and permanent MAD.

Neurobiology of Attention-Deficit/Hyperactivity Disorder and the Action Mechanism of OROS Methylphenidate

This article is to review neurobiology of attention-deficit/hyperactivity disorder (ADHD) and pharmacological properties of Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH)(Concerta Oros(R)) in celebration of its one-decade clinical experiences in Korea. ADHD is a highly heritable neurodevelopmental disorder, characterized by age-inappropriate inattention, hyperactivity and impulsiveness. The symptoms of ADHD are consistent with dysfunction of the prefrontal cortex (PFC). The PFC functions such as working memory and executive function are powerfully modulated by the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE). Methylphenidate (MPH) is a first line treatment for children and adolescents with ADHD in Korea. MPH improves the PFC functions with the mechanism of action being modulation of DA and NE tones by blocking both dopamine transporter (DAT) and norepinephrine transporter (NET). Stimulation of D1 and NE alpha2 receptors on the postsynaptic neurons may be its main mechanisms of action which improve working memory and behavioral inhibition in patients with ADHD. OROS MPH, one of long-acting MPH, employs an osmotic-releasing oral system (OROS), which has been designed to have 12 hour duration of effect, which permits oncedaily dosing, which has been shown to be as effective as 3-times-a-day immediate-release formulation of MPH (IR MPH). Recently there is growing evidence that OROS MPH has positive effects even on adults with ADHD, in multidimensional aspects; cognitively, emotionally and functionally.

Efficacy of OROS Methylphenidate for the Treatment of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is one of the common psychiatric problems in childhood. The symptoms of ADHD tend to last for adulthood and the patients suffer from various comorbid problems and functional impairments. Methylphenidate (MPH) is the first choice of pharmacotherapy for ADHD and many researches have demonstrated its efficacy. We reviewed the clinical trials for efficacy of MPH focusing on Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH). It was identified that MPH improved core symptom of ADHD, peer relationship and health related quality of life and might improve various aspects of cognitive function. It was proved that the efficacy of OROS MPH was better than placebo and comparable to immediate release MPH (IR MPH) dosed three times daily in various studies. Especially, parent's preference of OROS MPH was better than IR MPH. The efficacy of MPH for academic achievement was equivocal. Long-term efficacy of OROS MPH was also inconclusive and further study is necessary.

Neurobiology of Attention-Deficit/Hyperactivity Disorder and the Action Mechanism of OROS Methylphenidate

This article is to review neurobiology of attention-deficit/hyperactivity disorder (ADHD) and pharmacological properties of Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH)(Concerta Oros(R)) in celebration of its one-decade clinical experiences in Korea. ADHD is a highly heritable neurodevelopmental disorder, characterized by age-inappropriate inattention, hyperactivity and impulsiveness. The symptoms of ADHD are consistent with dysfunction of the prefrontal cortex (PFC). The PFC functions such as working memory and executive function are powerfully modulated by the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE). Methylphenidate (MPH) is a first line treatment for children and adolescents with ADHD in Korea. MPH improves the PFC functions with the mechanism of action being modulation of DA and NE tones by blocking both dopamine transporter (DAT) and norepinephrine transporter (NET). Stimulation of D1 and NE alpha2 receptors on the postsynaptic neurons may be its main mechanisms of action which improve working memory and behavioral inhibition in patients with ADHD. OROS MPH, one of long-acting MPH, employs an osmotic-releasing oral system (OROS), which has been designed to have 12 hour duration of effect, which permits oncedaily dosing, which has been shown to be as effective as 3-times-a-day immediate-release formulation of MPH (IR MPH). Recently there is growing evidence that OROS MPH has positive effects even on adults with ADHD, in multidimensional aspects; cognitively, emotionally and functionally.

Efficacy of OROS Methylphenidate for the Treatment of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is one of the common psychiatric problems in childhood. The symptoms of ADHD tend to last for adulthood and the patients suffer from various comorbid problems and functional impairments. Methylphenidate (MPH) is the first choice of pharmacotherapy for ADHD and many researches have demonstrated its efficacy. We reviewed the clinical trials for efficacy of MPH focusing on Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH). It was identified that MPH improved core symptom of ADHD, peer relationship and health related quality of life and might improve various aspects of cognitive function. It was proved that the efficacy of OROS MPH was better than placebo and comparable to immediate release MPH (IR MPH) dosed three times daily in various studies. Especially, parent's preference of OROS MPH was better than IR MPH. The efficacy of MPH for academic achievement was equivocal. Long-term efficacy of OROS MPH was also inconclusive and further study is necessary.

Effect of Methylphenidate on Sleep Parameters in Children with ADHD

OBJECTIVE: The primary aim of this study was to investigate the acute impact of methylphenidate (MPH) on sleep parameters in attention-deficit/hyperactivity disorder (ADHD) children. The second aim was to investigate the different effects of intermediate- and longacting MPH on sleep parameters. The third aim was to test the different effects of dose and age on sleep parameters. METHODS: Ninety-three ADHD children were enrolled and randomized to two different MPH preparations. Baseline and daily sleep diaries were evaluated for four weeks after taking medication. Weekday and weekend bedtimes, wake-up times, sleep latencies and total sleep times were compared by weeks. RESULTS: After taking MPH, there was a significant delay in bedtimes and a significant reduction of total sleep time (TST) both on weekdays and at weekends. There was also a significant delay in wake-up time on weekdays. However, the difference was applied to younger age group children only. There was no difference in changes of TST between metadate-CD and OROS-MPH. There also was no difference in changes of TST with different doses of MPH. CONCLUSION: MPH had negative impacts on sleep among young ADHD children, but different preparations and doses did not affect the result.

Clinical Characteristics of Methylphenidate Use in Korean Children and Adolescents with Autism Spectrum Disorder : A Retrospective Study

OBJECTIVES: The purpose of this study was to investigate clinical characteristics of children and adolescents with autism spectrum disorders (ASDs) using methylphenidate (MPH). METHODS: Retrospective review of the charts of 79 children and adolescents with ASDs, who visited the Department of Child and Adolescent Psychiatry of Seoul National Hospital, from July 2010 to July 2011, was conducted. Changes in illness severity and improvement were measured using the Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) Scales. RESULTS: We found that MPH was prescribed in 23 (29.1%) children and adolescents. Of the 23 patients on MPH, 4 patients (17.4%) were on MPH monotherapy and 18 patients (78.3%) were using risperidone concomitantly. MPH was prescribed primarily for symptoms of hyperactivity and impulsivity in ASDs patients. The mean dosage of MPH was 26.2+/-11.1mg/day and mean duration of treatment was 31.9+/-28.7 months. Mean CGI-S score improved significantly from baseline to endpoint (from 5.4+/-0.6 to 4.1+/-0.9 ; p<.01). MPH was reported to be effective in 17 patients (17/23, 73.9%), and 10 patients (10/23, 43.5%) reported side effects. Side effects included decreased appetite (4/23, 17.4%), tic (2/23, 8.6%), sleep disturbances (2/23, 8.6%), headache (1/23, 4.3%) and irritability (1/23, 4.3%). CONCLUSION: The results of this study demonstrate that MPH may be used effectively and safely in children and adolescents with ASDs with hyperactivity and impulsivity. Future controlled trials are needed to confirm these findings.

Synthesis and anti-tubercular activity of novel alkyl substituted riminophenazine derivatives / 药学学报

A series of novel riminophenazine derivatives bearing an alkyl substituent attached to N-5 and imino nitrogen at C-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. All target compounds were prepared by utilizing simple and flexible synthetic route and evaluated against Mycobacterium tuberculosis H37Rv and screened for mammalian cytotoxicity. The results demonstrated that compounds with a cyclopropyl substituent at N-5 position were more active than the reference compound clofazimine. In particular, 2-(4-chloroanilino)-5-cyclopropyl-3-(4-methoxycyclohexyl) imino-3, 5-dihydrophenazine (25) was found to be the most potent compound with low cytotoxicity and lipophilicity. This compound could serve as a valuable lead molecule for further optimization.

No Evidence of Association of the Alpha-2A-Adrenergic Receptor Gene with Methylphenidate Response in Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: The aim of this study was to examine the association of the ADRA2A MspI and DraI polymorphisms with methylphenidate (MPH) response in Korean children with ADHD. METHODS: The present study included 112 children and adolescents with ADHD (mean age=9.1+/-2.1 years), consisting of 92 boys (82.1%) and 20 girls (17.9%). ADHD was diagnosed based on the DSM-IV criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). For the clinical evaluation of the ADHD subjects, the ADHD Rating Scale-IV (ADHD-RS) and Clinical Global Impression (CGI) were administered at baseline and 8 weeks after MPH treatment. ADRA2A MspI and DraI polymorphisms were genotyped. The chi2 test was used to evaluate the relationship between the ADRA2A genotype and the response to MPH. The correlation between the genotype of ADRA2A and the change in the ADHD-RS scores after MPH treatment was assessed using the analysis of variance test and t-test. The significance level was set at p=0.01. RESULTS: No significant association was found between the genotypes of the ADRA2A MspI or DraI polymorphisms and MPH treatment response according to the CGI-improvement score (p>0.05). Comparing the changes in ARS scores after MPH treatment according to the genotypes of the MspI or DraI polymorphisms, we found no significant differences between subjects with different genotypes (p>0.05). CONCLUSION: Our results do not support the significant association between the MspI genotype and MPH response in Korean ADHD subjects, which was previously reported. In addition, we document no evidence of association between the DraI polymorphism and MPH treatment response in the Korean ADHD population.

Off-label use of Psychotropic Medications in Preschool Children with Attention-deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder with an onset of symptoms before 7 years of age, often starting as early as the preschool years. The off-label use of methylphenidate (MPH) for 3- to 6-year-old preschool children with ADHD is being more common, although MPH is not licensed for use in children younger than age 6 years, in most countries. Despite the limited data, the review of the literature suggests that MPH meets evidence based criteria as beneficial and safe for carefully diagnosed ADHD preschool children. Carefully monitored administration of evidence-based psychotropic medication in preschool children with ADHD may be indicated if psychosocial treatments are ineffective.