Choroidal thickness profile in healthy Indian children

Purpose:

The purpose was to study choroidal thickness and its profile based on location in healthy Indian children using enhanced depth spectral-domain-optical coherence tomography (SD-OCT).

Methods:

In this cross-sectional observational study 255 eyes of 136 children with no retinal or choroidal disease were consecutively scanned using enhanced depth SD-OCT. Eyes with any ocular disease or axial length (AXL) >25 mm or < 20 mm were excluded. A single observer measured choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microns intervals up to 2500 microns temporal and nasal to the fovea. Generalized estimating equations were used to evaluate the correlation between choroidal thickness at various locations and age, AXL, gender and spherical equivalent (SEq).

Results:

Mean age of the subjects was 11.9 ± 3.4 years (range: 5–18 years). There were 62 Females and 74 males. The mean AXL was 23.55 ± 0.74 mm. Mean subfoveal choroidal thickness was 312.1 ± 45.40 μm. Choroid was found to be thickest subfoveally, then temporally. Age, AXL and SEq showed a significant correlation with choroidal thickness, whereas gender did not affect choroidal thickness.

Conclusion:

Our study provides a valid normative database of choroidal thickness in healthy Indian children. This database could be useful for further studies evaluating choroidal changes in various chorioretinal disorders. Age and AXL are critical factors, which negatively correlated with choroidal thickness.     

Complete genome sequence analysis of Japanese encephalitis virus isolated from a horse in India

The complete genome of the Japanese encephalitis virus (JEV) strain JEV/eq/India/H225/2009(H225), isolated from an infected horse in India, was sequenced and compared to previously published JEV genomes. H225 genome was 10,977-nucleotides long, comprising a single ORF of 10,299-nucleotides, a 5′-UTR of 95 nucleotides and a 3′-UTR of 582 nucleotides. The H225 genome showed high levels of sequence identity with 47 fully sequenced JEV genomes, ranging from 99.3 % to 75.5 % for nucleotides and 99.2 % to 91.5 % for amino acid sequences. Phylogenetic analysis of the full-length sequence indicated that the H225 strain belongs to genotype III and is closely related to the Indian JEV strain Vellore P20778. A comparison of amino acids associated with neurovirulence in the E proteins and non-structural proteins of known virulent and attenuated JEV strains suggested H225 to be a highly virulent strain. This is the first report of whole-genome sequencing of a genotype III JEV genome isolated from equines.     

Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase- mediated cell death

Aim： Abrus agglutinin （AGG） from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo.
Methods： Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice.
Results： AGG induced apoptosis in HepG2 cells in a dose- and time-dependent manner. AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9 activities and a sharp decrease in the Bcl-2/Bax ratio, indicating activation of a caspase cascade. Co-treatment of HepG2 cells with AGG and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells decreased the caspase 3/7 activity in comparison to HepG2 cells exposed only to AGG. Moreover, AGG decreased the expression of Hsp90 and suppressed Akt phosphorylation and NF-κB expression in HepG2 cells. Finally, AGG treatment significantly reduced tumor growth in nude mice bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31 and Ki-67 expression compared to levels observed in the untreated control mice bearing HepG2 cells.
Conclusion： AGG inhibits the growth and progression of HepG2 cells by inducing caspase-mediated cell death. The agglutinin could be an alternative natural remedy for the treatment of human hepatocellular carcinomas.     

Metastatic Differentiated Thyroid Carcinoma: ClinicopathologicalProfile and Outcome in an Iodine Deficient Area

Reports on metastatic differentiated carcinoma in endemic goiter regions are scarce. The aim of this study was to look into the clinicopathological profile and outcome of patients with metastatic differentiated thyroid carcinoma (DTC) of endemic origin. This was a retrospective study of 28 cases of metastatic DTC out of a total of 140 DTC patients managed between 1990 and June 1999. Demographic data, clinicopathological profile, operative and radioiodine ablation therapy details, and follow-up findings were noted. The overall incidence of distant metastases in our series was 20%. Mean age was 48.5 +/- 12.8 years (32.1%patients were < 45 years). Most metastases were detected synchronously (85.7%) and were multiple, with the skeletal system being the commonly affected site. Out of 22 cases having skeletal metastases, 6 patients were young (< 45 years). Though most patients with skeletal metastases had follicular carcinoma (FTC), 4 cases had papillary thyroid cancer (PTC). Near total or total thyroidectomy was done in 26 cases. Sixteen patients required regional lymph node dissection. Resection of metastases was performed in 9 cases.Histopathological diagnosis was PTC, FTC, and poorly differentiated carcinoma in 32.1%, 50.0%, and 17.9% of cases, respectively. Most patients had good symptomatic palliation following administration of I131 therapy. In 17.9% of cases there were locoregional recurrences. There was an overall 28.6% mortality. Two patients expired in the perioperative period. Six others died in follow-up (all within 3-9 months). In contrast to iodine sufficient regions, the incidence of metastases was high; the majority of cases had synchronous, symptomatic skeletal metastases. Skeletal metastases were not infrequent even in cases of PTC and in young patients. One-third of the cases were young. Though survival was poor despite aggressive management, significant symptomatic palliation could be achieved in most cases.     

Role of alpha and beta adrenoceptors in locus coeruleus stimulation-induced reduction in rapid eye movement sleep in freely moving rats

Based on the results of independent studies the involvement of norepinephrine in REM sleep regulation was known. Isolated studies showed that the effect could be mediated through either one or more subtypes of adrenoceptors. Earlier we have reported that REM-OFF neurons continue firing during REM sleep deprivation and mild but continuous stimulation of locus coeruleus (LC) or picrotoxin injection into the LC, that did not allow the REM-OFF neurons in the LC to stop firing, reduced REM sleep. However, the mechanism of action and type of adrenoreceptors involved in REM sleep regulation were unknown. The possible mechanism of action has been investigated in this study. It was proposed that if LC stimulation-induced decrease in REM sleep was due to norepinephrine, adrenergic antagonist must prevent the effect. Therefore, in this study, the effects of alpha1, alpha2 and beta-antagonists, viz. prazosin, yohimbine and propranolol, respectively, and alpha2 agonist, clonidine, on LC stimulation-induced reduction in REM sleep were investigated. The results showed that stimulation of LC inhibited REM sleep by reducing the frequency of generation of REM sleep, although the duration per episode remained unaffected. This decrease in the frequency of REM sleep was blocked by beta-antagonist propranolol while the duration of REM sleep per episode was blocked by alpha1-antagonist, prazosin. Also, a critical level of norepinephrine in the system was required for the generation of REM sleep, however, a higher level may be inhibitory. Based on the results of this study and our earlier studies, an interaction between neurons, containing different neurotransmitters and their subtypes of receptors for LC-mediated regulation of REM sleep has been proposed.     

Ganglioneuroma of small bowel mesentery presenting as acute abdomen

Ganglioneuroma is a rare benign tumor, usually seen in children and young adults, arising in the central nervous system. Ganglioneuroma of the mesentery is extremely rare; only one case has been recorded. We report the second case of a primary mesentery ganglioneuroma. The patient underwent surgical intervention for diagnostic and therapeutic purposes.     

Isolation,structural determination,synthesis and quantitative determination of impurities in Intron-A,leached from a silicone tubing

Investigation of unexpected levels of impurities in Intron product has revealed the presence of low levels of impurities leached from the silicone tubing (Rehau RAU-SIK) on the Bosch filling line. In order to investigate the effect of these compounds (1a, 1b and 2) on humans, they were isolated identified and synthesized. They were extracted from the tubing by stirring in Intron placebo at room temperature for 72 h and were enriched on a reverse phase CHP-20P column, eluting with gradient aqueous ACN and were separated by HPLC. Structural elucidation of 1a, 1b and 2 by MS and NMR studies demonstrated them to be halogenated biphenyl carboxylic acids. The structures were confirmed by independent synthesis. Levels of extractable impurities in first filled vials of actual production are estimated to be in the range of 0.01–0.55 μg/vial for each leached impurity. Potential toxicity of these extractables does not represent a risk for patients under the conditions of clinical use.