A comprehensive analysis of selected medicines collected from private drug outlets of Dhaka city, Bangladesh in a simple random survey.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

The Phenotypic Spectrum of Tuberous Sclerosis Complex: A Canadian Cohort.

OBJECTIVE: We aimed to further elucidate the phenotypic spectrum of Tuberous Sclerosis Complex (TSC) depending on genotype. METHODS: A retrospective review of patients seen in the TSC clinic at the Hospital for Sick Children was conducted and the frequency of TSC manifestations was compared based on genotype. RESULTS: Nineteen-patients had TSC1 mutations, 36 had TSC2 mutations and 11 had no mutation identified (NMI). Patients with TSC2 mutations had a higher frequency of early-onset epilepsy and more frequent systemic manifestations. The NMI group had milder neurologic and systemic manifestations. Our data did not demonstrate that intellectual disability and infantile spasms were more common in TSC2 mutations. CONCLUSIONS: This is the first Canadian pediatric cohort exploring the genotype-phenotype relationship in TSC. We report that some manifestations are more frequent and severe in TSC2 mutations and that NMI may have a milder phenotype. Disease surveillance and counseling should continue regardless of genotype until this is better elucidated.

A Review of Investigations for Patients With Tuberous Sclerosis Complex Who Were Referred to the Tuberous Sclerosis Clinic at The Hospital for Sick Children: Identifying Gaps in Surveillance.

OBJECTIVE: As a newly established tuberous sclerosis clinic (TSC) clinic at The Hospital for Sick Children, we reviewed our referrals to determine if children with TSC received appropriate surveillance as advised by the 2012 International Tuberous Sclerosis Complex Consensus Recommendations. METHODS: We completed a retrospective review of all patients seen in the TSC clinic from January 2016 to December 2017 to determine if children referred to the clinic had appropriate surveillance as suggested by the Tuberous Sclerosis Complex Consensus Recommendations. RESULTS: Ninety patients were seen in the TSC clinic. The median age at first visit was 9.9 years, and 47 were males. Seventy-six percent had undergone genetic testing before the initial clinic visit; however, genetic counseling was completed in only 66%. Brain magnetic resonance imaging was completed in 94%, abdominal imaging was completed in 91%, and an echocardiography and electrocardiography in 88% and 83%, respectively. In addition, dermatology and ophthalmology evaluations were completed in 78% and 91%, respectively. Assessment of TSC-associated neuropsychiatric disorders (TAND) was only completed in 4% of the patients. CONCLUSIONS: Systems surveillance was completed in the majority before the first TSC clinic visit. However, TSC-associated neuropsychiatric disorder screening was completed in few cases. This suggests that referring physicians may not be familiar with the neuropsychiatric manifestations of TSC and that there may be underdiagnosed or undertreated illness. Future emphasis should be placed on educating all practitioners to assess and treat tuberous sclerosis complex-associated neuropsychiatric disorder in tuberous sclerosis complex.

A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.

INTRODUCTION: Both Δ9 Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects. Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy. Primary objective was to establish dosing and tolerability of TIL-TC150 - a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life. METHODS: Twenty children received add-on therapy with TIL-TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events, and secondary objectives. RESULTS: Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%. CONCLUSIONS: TIL-TC150 was safe and well tolerated in our subjects. TIL-TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC-containing cannabinoid preparations.

Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT.

Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy. As determined by fluorescence staining and Western blots, the combination of the two drugs inhibited the phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) together with the expression of antiapoptotic proteins including myeloid leukemia cell differentiation protein Mcl-1 (Mcl-1) and apoptosis regulator Bcl-2 (Bcl-2), resulting in the death of cancer cells. We also found that the combination inhibited the formation and self-renewal of HCC stem cells by down-regulating the expression of stemness-related proteins, such as Homeobox protein NANOG (Nanog) and Krueppel-like factor 4 (Klf4). These results suggested that silibinin improved the efficacy of sorafenib in HCC therapy, indicating a clinical promising therapeutic strategy for HCC patients.

Picture Novelty Influences Response Selection and Inhibition: The Role of the In-Group Bias and Task-Difficulty.

The human visual system prioritizes processing of novel information, leading to faster detection of novel stimuli. Novelty facilitates conflict resolution through the enhanced early perceptual processing. However, the role of novel information processing during the conflict-related response selection and inhibition remains unclear. Here, we used a face-gender classification version of the Simon task and manipulated task-difficulty and novelty of task-relevant information. The novel quality of stimuli was made task-irrelevant, and an in-group bias was tightly controlled by manipulation of a gender of picture stimuli. We found that the in-group bias modulated the role of novelty in executive control. Novel opposite-sex stimuli facilitated response inhibition only when the task was not demanding. By contrast, novelty enhanced response selection irrespective of the in-group factor when task-difficulty was increased. These findings support the in-group bias mechanism of visual processing, in cases when attentional resources are not limited by a demanding task. The results are further discussed along the lines of the attentional load theory and neural mechanisms of response-inhibition and locomotor activity. In conclusion, our data showed that processing of novel information may enhance executive control through facilitated response selection and inhibition.

Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice.

Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits.