Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Subacute sclerosing panencephalitis resembling Rasmussen’s encephalitis on magnetic resonance imaging

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen’s encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.     

Primary exophytic laryngeal amyloidosis presenting as sudden airway obstruction

Primary amyloidosis of larynx is an uncommon phenomenon, the precise etiopathogenesis of which is not yet clear. It can present with slowly increasing hoarseness or difficulty in breathing. It presents more commonly as infiltrative lesion, exophytic presentation is a rare occurrence.     

Intraobserver and interobserver variation in the sonographic grading of placental maturity.

OBJECTIVES: The appearance of Grannum Grade III changes in the placenta at around 34-36 weeks is a predictor of adverse perinatal outcome, which may be reduced by reporting to the clinician. This has led to the suggestion that the placental grade should be noted during any third-trimester scan. There are no published data on the reproducibility of sonographic Grannum grading of the placenta; the objective of this study was to evaluate intra- and interobserver variation. METHODS: Fifty-five placental images from normal and complicated pregnancies of several different gestational ages were collected between April and October 2001. Three fetal medicine consultants and three experienced sonographers graded the images as 0, I, II, III or ungradeable. They then regraded the same images, presented in a different order and with different codes, 4-6 weeks later. Observers were blinded to their previous grading and to each others'. Weighted kappa (kappa), with linear weights, was used to look for strength of agreement. RESULTS: There was good agreement between the two observations of each placental image for five observers (kappa = 0.61 to 0.90), and moderate agreement for one observer (kappa = 0.56). However, the kappa-values for comparisons between the 15 pairs of observers ranged from 0.24 to 0.69 with six values below 0.41, indicating only fair agreement. This was confirmed by the overall kappa-value of 0.24 between all six observers. The agreement between the observers for Grade III placenta was poor, with an overall kappa-value of 0.09. CONCLUSIONS: Although intraobserver agreement was generally good, interobserver agreement was only fair for all grades and poor for Grade III placenta. This may be an indication that Grannum grading is not reproducible or it may reflect a need for training in those performing grading. Such variation may limit the effectiveness of reporting Grannum grades in clinical practice.     

Primary malignant melanoma of cervix: a case report

Primary malignant melanoma of cervix is a rare entity. A case of primary malignant melanoma of cervix presented with vaginal discharge and black colored growth over cervix. Histology showed malignant pleomorphic cells with melanin pigment in the cytoplasm.     

Presence of two Ca2+ influx components in internal Ca2+-pool-depleted rat parotid acinar cells

The molecular mechanism(s) involved in mediating Ca²⁺ entry into rat parotid acinar and other non-excitable cells is not known. In this study we have examined the kinetics of Ca²⁺ entry in fura-2-loaded parotid acinar cells, which were treated with thapsigargin to deplete internal Ca²⁺ pools (Ca²⁺-pool-depleted cells). The rate of Ca²⁺ entry was determined by measuring the initial increase in free cytosolic [Ca²⁺] ([Ca²⁺]_i) in Ca²⁺-pool-depleted, and control (untreated), cells upon addition of various [Ca²⁺] to the medium. In untreated cells, a low-affinity component was detected with K _Ca = 3.4 ± 0.7 mM (where K _Ca denotes affinity for Ca²⁺) and V _max = 9.8 ± 0.4 nM [Ca²⁺]_i/s. In thapsigargin-treated cells, two Ca²⁺ influx components were detected with K _Ca values of 152 ±  79 μM (V _max = 5.1 ± 1.9 nM [Ca²⁺]_i/s) and 2.4 ±  0.9 mM (V _max = 37.6 ± 13.6 nM [Ca²⁺]_i/s), respectively. We have also examined the effect of Ca²⁺ and depolarization on these two putative Ca²⁺ influx components. When cells were treated with thapsigargin in a Ca²⁺-free medium, Ca²⁺ influx was higher than into cells treated in a Ca²⁺-containing medium and, while there was a 46% increase in the V _max of the low-affinity component (no change in K _Ca), the high-affinity component was not clearly detected. In depolarized Ca²⁺-pool-depleted cells (with 50 mM KCl in the medium) the high-affinity component was considerably decreased while there was an apparent increase in the K _Ca of the low-affinity component, without any change in the V _max. These results demonstrate that Ca²⁺ influx into parotid acinar cells (1) is increased (four- to five-fold) upon internal Ca²⁺ pool depletion, and (2) is mediated via at least two components, with low and high affinities for Ca²⁺. Received: 30 October 1995/Received after revisionand accepted: 13 December 1995     

Studies on codon usage in Thermoplasma acidophilum and its possible implications on the occurrences of lateral gene transfer

Codon usage studies have been carried out on the coding sequences of Thermoplasma acidophilum, which is an archaeon and grows at very low pH and high temperature. Overall codon usage data analysis indicates that all the four bases are almost equifrequent at the third position of codons, which is expected (since genomic GC % of this genome is about 46%). However, multivariate statistical analysis indicates that there are two major trends in the codon usage variation among the genes in this organism. In the first major trend it is observed that genes having G and C ending codons are clustered at one end while, A and T ending ones are clustered at the other end. We have also found a significant positive correlation between the expressivities of genes and GC contents at the synonymous third codon positions. In the second major trend, it is seen that the genes are clustered into three distinct parts. A comparative analyses of codon usage data of T. acidophilum and Sulfolobus solfataricus reveals that one of the three clusters of genes of T. acidophilum is very similar to a considerable number of S. solfataricus genes, suggesting possible occurrences of lateral gene transfer between these two microorganisms as reported by earlier workers.     

Development and validation of a CGH microarray for clinical cytogenetic diagnosis.

PURPOSE: We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH). METHODS: The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference. RESULTS: The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%. Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory. CONCLUSION: The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype. Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism.