Cellular injury and neuroinflammation in children with chronic intractable epilepsy

Objective  

To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.     

Ameliorative effects of tinospora cordifolia root extract on histopathological and biochemical changes induced by aflatoxin-b(1) in mice kidney

The present study was planned to investigate the ability of the Tinospora cordifolia to scavenge free radicals generated during aflatoxicosis. A total no. of 48 male Swiss albino mice (30 ± 5 g) were exposed to Aflatoxin B(1)(AFB(1)) (2 μg/30 g b.wt, orally) either individually or in combination with T. cordifolia (50, 100, 200 mg/kg, orally) once daily for 25 days. AFB(1) exposure led to significant rise in thiobarbituric acid reactive substances (TBARS) and fall in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), ascorbic acid, and protein content. T. cordifolia was found to show protective effect by lowering down the content of TBARS and enhancing the GSH, ascorbic acid, protein, and the activities of antioxidant enzymes viz., SOD, CAT, glutathione peroxidase, GST, and GR in kidney. Histopathological analysis of kidney samples also confirmed the protective values and antioxidant activity of ethanolic extract of herb. T. cordifolia showed protection against aflatoxin-induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine.     

Pharmacologic management of high-risk neuroblastoma in children

Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Children with high-risk disease have a 3-year event-free survival rate of only 20%. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. The aim of this article was to review and critically evaluate the pharmacotherapy of neuroblastoma, using peer reviewed and review literature from 2000-11. All peer reviewed, published human subject studies of therapy for neuroblastoma in children were included. Animal model and in vitro studies were included only if they added to the understanding of the mechanism of a proposed or existing human neuroblastoma therapy. Current therapeutic options for neuroblastoma involve insufficient differentiation of normal from neoplastic tissue. Critically needed new approaches will increasingly exploit targeting of therapy for unique characteristics of the neuroblastoma cell. Pharmacotherapy for neuroblastoma still suffers from an inadequate therapeutic window. Enhancement of toxicity for tumor and safety for normal tissues will entail innovation in targeting neuroblastoma cells and rescuing or protecting normal tissue elements.     

Molecular characterization of late stomal recurrence following total laryngectomy

The goal was to determine recurrent or second primary status for late stomal malignancies, 16 and 17 years post-total laryngectomy in two laryngeal squamous cell carcinoma (LSCC) patients, based on DNA methylation signatures and HPV typing. Adopting a literature review based definition of late stomal recurrences as new primaries at the site of the stoma or neopharynx occurring >5 years after total laryngectomy, we employed a multi-gene candidate approach to examine promoter methylation in 24 tumor suppressor genes and PCR-based assays for HPV status offered additional insights into whether the late stomal tumors post-total laryngectomy were related or not. The primary tumor for Patient 1 was negative for HPV but had aberrant hypermethylation of APC, MLH1 and BRCA1. The stomal biopsy 17-years later showed presence of HPV-16 without any methylated genes. In Patient 2, HPV-11 and promoter methylation of APC identified in the primary tumor was also observed in the stomal malignancy 16 years post-total laryngectomy. Additional information provided by molecular typing for HPV and methylation markers underscored Patient 1's and 2's late stomal presentation as most likely a second primary and recurrence, respectively. DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable marker. Molecular marks to discern genetic heterogeneity or relatedness of stomal malignancies several years post-total laryngectomy can provide clues to their status as either second primaries or likely recurrences. Our results support the hypothesis that a subset of stomal recurrences after total laryngectomy represents second primary tumors.     

Maternal weight and lean body mass may influence the lactation-related bone changes in young undernourished Indian women

Lactation is known to be associated with a transient loss of bone mineral density (BMD) during 3-6 months post-partum. Bone changes during lactation in women consuming low dietary calcium are not sufficiently studied. The present longitudinal study examined the BMD changes during lactation in undernourished women and the relationship of bone changes to the nutritional status. Whole-body bone mineral content and BMD at hip, lumbar spine and forearm were assessed using dual-energy X-ray absorptiometry in thirty-six lactating women from the low socio-economic group at four time points -- within 1 month after delivery (baseline), and at 6, 12 and 18 months after delivery. Maternal body composition and biochemical parameters of bone metabolism were estimated at the same time. It was observed that femoral neck BMD reduced by 4.6 % at 6 months, but recovery to the baseline was incomplete at 18 months with a deficit of 2 %. Hip BMD reduction at 6 months was transient. Lumbar spine BMD did not show significant loss at 6 months and BMD increased by 3.6 and 6.3 % at 12 and 18 months, respectively. Regression analyses indicated that baseline lean mass was the most important determinant of bone preservation at femoral neck, hip as well as whole body, whereas baseline body weight was the most important determinant of per cent gain in lumbar spine. Maternal nutritional status as indicated by body weight and lean mass appears to influence the lactation-related BMD changes in undernourished women from the low socio-economic group in India.     

Cortical grey matter volume and sensorimotor gating in schizophrenia

Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable tool to study the known inability of a large proportion of individuals with schizophrenia to effectively screen out irrelevant sensory input. The cortico-striato-pallido-thalamic circuitry is thought to be responsible for modulation of PPI in experimental animals. The involvement of this circuitry in human PPI is supported by observations of deficient PPI in a number of neuropsychiatric disorders that are characterised by abnormalities at some level in this circuitry, and findings of recent functional neuroimaging studies in healthy participants. The current study sought to investigate the structural neural correlates of PPI in a sample of 42 stable male outpatients with schizophrenia. Participants underwent magnetic resonance imaging (MRI) at 1.5T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimised volumetric voxel-based morphometry implemented in SPM2 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120msec) to regional grey matter (GM) volumes. Significant positive correlations were obtained between PPI and GM volume in the dorsolateral prefrontal, middle frontal and the orbital/medial prefrontal cortices. Our findings are consistent with (a) previous suggestions of susceptibility of PPI to cognitive processes controlled in a 'top down' manner by the cortex and (b) the hypothesis that compromised neural resources in the frontal cortex contribute to reduced PPI in schizophrenia.     

Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure-neuropsychological function relationships.     

Cystic white-matter changes in childhood Wilson's disease

Altered signals in magnetic resonance imaging are present in most symptomatic patients with neurologic manifestations of Wilson's disease. The changes primarily involve the basal ganglia, but they can be diverse and can involve a host of other structures. We describe a 12-year-old boy with Wilson's disease who manifested prominent white-matter cystic changes. These changes can cause diagnostic confusion, and may also present prognostic implications.