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1.
Neurobiol Dis ; 147: 105147, 2021 01.
Article in English | MEDLINE | ID: mdl-33189882

ABSTRACT

Oxytocin (OT) has broad effects in the brain and plays an important role in cognitive, social, and neuroendocrine function. OT has also been identified as potentially therapeutic in neuropsychiatric disorders such as autism and depression, which are often comorbid with epilepsy, raising the possibility that it might confer protection against the behavioral and seizure phenotypes in epilepsy. Dravet syndrome (DS) is an early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), treatment-resistant afebrile epilepsy, and cognitive and behavioral deficits. De novo loss-of-function mutations in the voltage-gated sodium channel SCN1A are the main cause of DS, while genetic epilepsy with febrile seizures plus (GEFS+), also characterized by early-life FSs and afebrile epilepsy, is typically caused by inherited mutations that alter the biophysical properties of SCN1A. Despite the wide range of available antiepileptic drugs, many patients with SCN1A mutations do not achieve adequate seizure control or the amelioration of associated behavioral comorbidities. In the current study, we demonstrate that nanoparticle encapsulation of OT conferred robust and sustained protection against induced seizures and restored more normal social behavior in a mouse model of Scn1a-derived epilepsy. These results demonstrate the ability of a nanotechnology formulation to significantly enhance the efficacy of OT. This approach will provide a general strategy to enhance the therapeutic potential of additional neuropeptides in epilepsy and other neurological disorders.


Subject(s)
Behavior, Animal/drug effects , NAV1.1 Voltage-Gated Sodium Channel/genetics , Oxytocin/administration & dosage , Seizures , Animals , Epilepsies, Myoclonic/genetics , Male , Mice , Nanoparticles , Seizures/genetics , Social Behavior
2.
Trans R Soc Trop Med Hyg ; 110(6): 367-72, 2016 06.
Article in English | MEDLINE | ID: mdl-27358288

ABSTRACT

BACKGROUND: Faecal-oral carriage via hands is an important transmission pathway for diarrhoeal pathogens. The level of faecal contamination of commuters' hands in Dhaka, Bangladesh, was examined in this study. METHODS: A total of 900 hand washing samples, including both left and right hands, were collected during one year to cover three different seasons in Bangladesh: winter, summer and rainy seasons. Standard membrane filtration technique was used to quantify total coliforms (TC), faecal coliforms (FC), faecal streptococci (FS), Escherichia coli (EC) and Clostridium perfringens (CP). RESULTS: The hands of the commuters were contaminated with TC, FC, FS, CP and EC. The TC, FC, FS, CP and EC counts were 1.95, 1.65, 4.04, 1.54 and1.46 log10 colony forming units (cfu) in the left hand; and 2.13, 1.82, 4.11, 1.52 and 1.61 log10 cfu in the right hand, respectively. There were no statistically significant differences in counts of left and right hands. The highest counts were observed for FS in all seasons. CONCLUSIONS: This evidence based study may be used to provide interventions to reduce the contamination of commuters' hands through washing with detergent and, thus, help to prevent the spread of infectious diseases.


Subject(s)
Bacterial Infections/transmission , Cities , Feces/microbiology , Hand Disinfection , Hand/microbiology , Transportation , Water Microbiology , Bangladesh , Clostridium perfringens , Escherichia coli , Humans , Seasons , Streptococcus
3.
Trans R Soc Trop Med Hyg ; 108(11): 715-20, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25233936

ABSTRACT

BACKGROUND: This study describes phenotypic, genotypic and antibiotic susceptibility patterns of the strains isolated from the 2012 Sierra Leone cholera outbreak. Rectal swabs were collected from patients and cultured for Vibrio cholerae O1. METHODS: The isolates were subjected to multiplex PCR, mismatch amplification mutation assay (MAMA) PCR, pulsed field gel electrophoresis (PFGE), and antibiotic sensitivity tests using disk diffusion and minimum inhibitory concentration (MIC) E-test following standard procedures. RESULTS: Out of 17 rectal swabs tested, 15 yielded V. cholerae O1 biotype El Tor, serotype Ogawa. All the strains belonged to 'altered' variants as MAMA PCR result showed the presence of classical cholera toxin B. PFGE result revealed four pulse types. Using antibiotic disk diffusion, all the isolates were resistant to erythromycin, chloramphenicol, furazolidone, and trimethoprim/sulfamethoxazole (SXT) except SL1 which was sensitive to chloramphenicol and SXT. All the isolates were sensitive to nalidixic acid, tetracycline, doxycycline, azithromycin, and ciprofloxacin except SL2 which was resistant to nalidixic acid. However, variable sensitivity patterns were observed for kanamycin. The ranges of MIC were 0.125-0.50 mg/l, 0.003-0.023 mg/l and 0.38-0.75 mg/l for azithromycin, ciprofloxacin and tetracycline, respectively. CONCLUSIONS: This study demonstrates that altered variants of V. cholerae O1 of four clonal types were responsible for the 2012 outbreak of cholera in Sierra Leone.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cholera , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Vibrio cholerae O1/drug effects , Vibrio cholerae O1/genetics , Azithromycin/pharmacology , Bacterial Typing Techniques , Cholera/drug therapy , Cholera/epidemiology , Cholera/microbiology , Ciprofloxacin/pharmacology , Disease Outbreaks , Dose-Response Relationship, Drug , Electrophoresis, Gel, Pulsed-Field , Genotype , Humans , Microbial Sensitivity Tests , Sierra Leone/epidemiology , Tetracycline/pharmacology , Vibrio cholerae O1/classification , Vibrio cholerae O1/isolation & purification
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