Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo Investigation of Hepatoprotective, Antioxidant Activity and Bioavailability Study in Rats.

The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media. The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl4)-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.

Combined MEG-EEG source localisation in patients with sub-acute sclerosing pan-encephalitis.

To study the genesis and propagation patterns of periodic complexes (PCs) associated with myoclonic jerks in sub-acute sclerosing pan-encephalitis (SSPE) using magnetoencephalography (MEG) and electroencephalography (EEG). Simultaneous recording of MEG (306 channels) and EEG (64 channels) in five patients of SSPE (M:F = 3:2; age 10.8 ± 3.2 years; symptom-duration 6.2 ± 10 months) was carried out using Elekta Neuromag(®) TRIUX™ system. Qualitative analysis of 80-160 PCs per patient was performed. Ten isomorphic classical PCs with significant field topography per patient were analysed at the 'onset' and at 'earliest significant peak' of the burst using discrete and distributed source imaging methods. MEG background was asymmetrical in 2 and slow in 3 patients. Complexes were periodic (3) or quasi-periodic (2), occurring every 4-16 s and varied in morphology among patients. Mean source localization at onset of bursts using discrete and distributed source imaging in magnetic source imaging (MSI) was in thalami and or insula (50 and 50 %, respectively) and in electric source imaging (ESI) was also in thalami and or insula (38 and 46 %, respectively). Mean source localization at the earliest rising phase of peak in MSI was in peri-central gyrus (49 and 42 %) and in ESI it was in frontal cortex (52 and 56 %). Further analysis revealed that PCs were generated in thalami and or insula and thereafter propagated to anterolateral surface of the cortices (viz. sensori-motor cortex and frontal cortex) to same side as that of the onset. This novel MEG-EEG based case series of PCs provides newer insights for understanding the plausible generators of myoclonus in SSPE and patterns of their propagation.

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.

Alcohol harm to adolescents from others' drinking: A study from Kerala, India.

CONTEXT: There is scarce data on the prevalence of harm to adolescents from others' use of alcohol from India. AIMS: The aim is to study the prevalence of harm to school students from others' alcohol use in the district of Ernakulam, Kerala and examines its psychosocial correlates among victims. SETTINGS AND DESIGN: This was a cross-sectional survey of 7560 students of the age range of 12-19 years from 73 schools. MATERIALS AND METHODS: Harm consequent to others' drinking was assessed using a brief version of the World Health Organization-Thai Health Questionnaire on Harm to Others from Drinking. Standardized instruments were used to assess other measures. STATISTICAL ANALYSIS: The prevalence of various harms was determined. Mixed-effect logistic regression was used to explore the sociodemographic, academic, and psychological factors associated with various types of harms and odds ratios reported. RESULTS: Harm due to others' alcohol use was reported by 44.5%, frequent harm by 15.7%, psychological harm by 43.3%, physical harm by 9.7%, property harm by 2.9%, and financial harm by 15.4%. Boys reported greater harm than girls. Girls experienced relatively greater harm within the family and boys outside the family. Being older, having a part-time job and urban residence increased the odds of harm. Adolescents reporting harm had higher odds of substance use, psychological distress, suicidality, sexual abuse, and attention-deficit/hyperactivity disorder symptom-counts. CONCLUSION: The high prevalence of harm from others alcohol use to adolescents with multiple negative impacts underscore the urgent need for public health measures to reduce social costs of alcohol use.

NREM Sleep and Antiepileptic Medications Modulate Epileptiform Activity by Altering Cortical Synchrony.

INTRODUCTION: The activating role of non-rapid eye movement (NREM) sleep on epileptic cortex and conversely, the seizure remission brought about by antiepileptic medications, has been attributed to their effects on neuronal synchrony. This study aims to understand the role of neural synchrony of NREM sleep in promoting interictal epileptiform discharges (IEDs) in patients with epilepsy (PWE) by assessing the peri-IED phase synchrony during awake and sleep states. It also studies the role played by antiepileptic drugs (AEDs) on EEG desynchronization in the above cohort. METHODS: A total of 120 PWE divided into 3 groups (each n = 40; juvenile myoclonic epilepsy [JME], temporal lobe epilepsy [TLE]. and extratemporal lobe epilepsy [Ex-TLE]) were subjected to overnight polysomnography. Each patient group was subdivided into drug-naive and on treatment (Each n = 20). EEG phase synchronization analysis was performed to compare peri-IED phase synchronization indices (SI) during awake and sleep stages and between drug naïve and on treatment groups in 4 frequency bands, namely delta, theta, alpha, and beta. The mean ± SD of peri-IED SI among various subgroups was compared employing a multilevel mixed effects modeling approach. RESULTS: Patients with JME had increased peri-IED cortical synchrony in N3 sleep stage, whereas patients with partial epilepsy had increased IED cortical synchrony in N1 sleep stage. On the other hand, peri-IED synchrony was lower during wake and REM sleep. We also found that peri-IED synchronization in patients with JME was higher in drug-naive patients compared with those on sodium valproate monotherapy in theta, alpha, and beta bands. CONCLUSION: The findings of this study suggest that sleep stages can alter cortical synchrony in patients with JME and focal epilepsy, with NREM IEDs being more synchronized and wake/REM IEDs being less synchronized. Furthermore, it also suggests that AEDs alleviate seizures in PWE by inhibiting cortical synchrony.

Heightened Background Cortical Synchrony in Patients With Epilepsy: EEG Phase Synchrony Analysis During Awake and Sleep Stages Using Novel Ensemble Measure.

INTRODUCTION: Excessive cortical synchrony within neural ensembles has been implicated as an important mechanism driving epileptiform activity. The current study measures and compares background electroencephalographic (EEG) phase synchronization in patients having various types of epilepsies and healthy controls during awake and sleep stages. METHODS: A total of 120 patients with epilepsy (PWE) subdivided into 3 groups (juvenile myoclonic epilepsy [JME], temporal lobe epilepsy [TLE], and extra-temporal lobe epilepsy [Ex-TLE]; n = 40 in each group) and 40 healthy controls were subjected to overnight polysomnography. EEG phase synchronization (SI) between the 8 EEG channels was assessed for delta, theta, alpha, sigma, and high beta frequency bands using ensemble measure on 10-second representative time windows and compared between patients and controls and also between awake and sleep stages. Mean ± SD of SI was compared using 2-way analysis of variance followed by pairwise comparison ( P ≤ .05). RESULTS: In both delta and theta bands, the SI was significantly higher in patients with JME, TLE, and Ex-TLE compared with controls, whereas in alpha, sigma, and high beta bands, SI was comparable between the groups. On comparison of SI between sleep stages, delta band: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3, whereas REM (rapid eye movement) was comparable to wake; theta band: decreased SI during N2 and increase during N3; alpha band: SI was highest in wake and lower in N1, N2, N3, and REM; and sigma and high beta bands: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3; however, sigma band showed lower SI during REM. CONCLUSION: This study found an increased background cortical synchronization in PWE compared with healthy controls in delta and theta bands during wake and sleep. This background hypersynchrony may be an important property of epileptogenic brain circuitry in PWE, which enables them to effortlessly generate a paroxysmal EEG depolarization shift.

Cerebral and Coronary Vasculature in Disease Associations and Dissociations in the South Indian Population.

INTRODUCTION: Cerebrovascular accidents constitute the most common cause of disability all over the world. In India prevalence rate is 545 per 100000 and mortality rate is around 7.5 per thousand. Therefore the authors undertook a study on patients who underwent coronary artery bypass surgery (CABG). They were investigated for clinical and/or radiological evidence of cerebrovascular disease (CVD) with the aim to decide on early neurological intervention. PATIENTS AND METHODS: 210 patients who had undergone CABG were evaluated with neck vessel Doppler using high resolution duplex scanner system and computed tomography (CT) scan as well as MR angiogram (MRA) in addition to assessment of co morbid risk factors. RESULTS: 91% of patients who had undergone CABG had radiological evidence of CVD. The most common risk associated with CAD and CVD was Hypertension (HT), DM, dyslipidemia and combined HT and DM in that order. Neck vessels were normal in 59%. Significant disease was found in only 7.2%. Internal carotids were abnormal in 82%. Infarcts were seen in 82.1%. DISCUSSION: This study reveals patients with CAD have a high degree of asymptomatic CVD. It is mostly due to small vessel disease including internal carotids but not so much with large vessels. Therefore, patients with CAD carry a high risk of vascular cognitive dysfunction. This can be reduced by effective management of the systemic risk factors. Screening for large vessel disease which is commonly done is likely to give a false sense of security. CONCLUSION: As against western population Indians seem to have small and medium sized vessels disease in the setting of CAD.

Non Diphtheritic Corynebacteria: An Emerging Nosocomial Pathogen in Skin and Soft Tissue Infection.

INTRODUCTION: Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens. AIM: To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents. MATERIALS AND METHODS: Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. RESULTS: C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species. CONCLUSION: Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available.