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.
Animals ; Anti-Bacterial Agents ; chemistry ; metabolism ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Crystallography, X-Ray ; Insecta ; microbiology ; Magnetic Resonance Spectroscopy ; Microbial Sensitivity Tests ; Micrococcus luteus ; drug effects ; Molecular Structure ; Multigene Family ; Phenazines ; chemistry ; metabolism ; pharmacology ; Streptomyces ; chemistry ; genetics ; metabolism

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.

Human ; Female ; Adult (a Person 19-44 Years Of Age) ; Adolescent (a Person 13-18 Years Of Age) ; Gardnerella Vaginalis ; Vaginosis, Bacterial ; Metronidazole ; Lactobacillus ; Gardnerella ; Probiotics ; Vaginal Discharge ; Gentian Violet ; Phenazines ; Tablets ; Anti-bacterial Agents

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.

Human ; Female ; Adult ; Adolescent ; Gardnerella Vaginalis ; Vaginosis, Bacterial ; Metronidazole ; Lactobacillus ; Gardnerella ; Probiotics ; Vaginal Discharge ; Gentian Violet ; Phenazines ; Tablets ; Anti-bacterial Agents

Gentian Violet ; Humans ; Iatrogenic Disease ; Phenazines ; Pneumonia, Bacterial ; diagnosis ; Sputum ; microbiology

Anti-Bacterial Agents ; therapeutic use ; Gentian Violet ; Humans ; Phenazines ; Pneumonia, Bacterial ; diagnosis ; drug therapy ; microbiology

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.
Adolescent ; Adolescent Psychiatry ; Appetite ; Autistic Disorder ; Child ; Autism Spectrum Disorder ; Headache ; Humans ; Methylphenidate ; Phenazines ; Retrospective Studies ; Risperidone ; Tics

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.
Child ; Humans ; Methylphenidate ; Phenazines

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.
Animals ; Antitubercular Agents ; chemical synthesis ; chemistry ; pharmacology ; Cercopithecus aethiops ; Drug Design ; Microbial Sensitivity Tests ; Molecular Structure ; Mycobacterium tuberculosis ; drug effects ; Phenazines ; chemical synthesis ; chemistry ; pharmacology ; Vero Cells

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.
Achievement ; Humans ; Methylphenidate ; Phenazines ; Quality of Life

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.
Adolescent ; Adult ; Child ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Executive Function ; Humans ; Korea ; Memory, Short-Term ; Methylphenidate ; Neurobiology ; Neurons ; Neuropharmacology ; Neurotransmitter Agents ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Phenazines ; Prefrontal Cortex