Study - Failure of titer of contact hypersensitivity to correlate with clinical severity and therapeutic response in contact dermatitis caused by parthenium

Background: The titer of contact hypersensitivity (TCH) has been used to determine the degree of contact hypersensitivity in patients with contact dermatitis. The values have been found to vary in different individuals and also in the same individual at different times apparently due to the varying severity of the disease. We evaluated the correlation of TCH with disease severity and therapeutic response in patients of contact dermatitis caused by the plant Parthenium hysterophorus . Methods: Forty-two patients, 30 (71.4%) males and 12 (28.6%) females, aged between 30-75 years, having air-borne contact dermatitis to Parthenium hysterophorus for 0.5-20 years were included in the study. The disease severity and TCH at baseline were recorded in all the patients. They were treated with azathioprine and followed up every month for 4-69 months. The TCH was repeated every 3 months and the last recorded TCH value was taken for analysis in each patient. Results: The baseline clinical severity score (CSS) varied from 10-80 (mean \ub1 SD: 35.47 \ub1 19.41) in these patients. It ranged from 10-30 in 22 (52.4%) patients, from 31-50 in 14 (33.3%) patients, and was more than 50 in 6 (14.3%) patients. The baseline TCH to Parthenium was undiluted (UD) in 2 (4.8%), 1:10 in 15 (35.7%), 1:100 in 20 (47.6%), and 1:1000 in 5 (11.9%) patients respectively. At the end of the study, the clinical severity of the disease decreased in most of the patients. The CSS came down to 0 in 31 patients, to 10-20, and to 50 in 4 patients each, but remained stable in three patients who had baseline CSS from 20-40. The overall mean CSS came down from 35.47 \ub1 19.41 to 4.76 \ub1 9.43 (p = 0.002). However, there was no significant change in the TCH levels over time (p = 0.153). The last TCH value was negative in 2 (4.8%) patients, undiluted in 5 (11.9%), 1:10 in 10 (23.8%), 1:100 in 18 (42.9%), and 1:1000 in 7 (16.7%) patients. There was no change in the TCH values in 16 (38.1%) patients while it increased or decreased by 1-2 dilutions in 12 (28.6%) patients each. Conclusions: We therefore conclude that the TCH does not correlate with the clinical severity of contact dermatitis or response to treatment

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

14-3-3epsilon contributes to tumour suppression in laryngeal carcinoma by affecting apoptosis and invasion

<p>Abstract</p> <p>Background</p> <p>14-3-3epsilon regulates a wide range of biological processes, including cell cycle control, proliferation, and apoptosis, and plays a significant role in neurogenesis and the formation of malignant tumours. However, the exact function and regulatory mechanism of 14-3-3epsilon in carcinogenesis have not been elucidated.</p> <p>Methods</p> <p>The expression of <it>14-3-3epsilon </it>was assessed by RT-PCR and western blotting. The invasiveness and viability of Hep-2 cells were determined by the transwell migration assay and MTT assay, respectively. Cell cycle and apoptosis of Hep-2 cells were detected by flow cytometry.</p> <p>Results</p> <p>The mRNA and protein expression of <it>14-3-3epsilon </it>in larynx squamous cell carcinoma (LSCC) tissues were significantly lower than those in clear surgical margin tissues. Statistical analysis showed that the 14-3-3epsilon protein level in metastatic lymph nodes was lower than that in paired tumour tissues. In addition, the protein level of 14-3-3epsilon in stage III or IV tumours was significantly lower than that in stage I or II tumours. Compared with control Hep-2 cells, the percentages of viable cells in the 14-3-3epsilon-GFP and negative control GFP groups were 36.68 ± 14.09% and 71.68 ± 12.10%, respectively. The proportions of S phase were 22.47 ± 3.36%, 28.17 ± 3.97% and 46.15 ± 6.82%, and the apoptotic sub-G1 populations were 1.23 ± 1.02%, 2.92 ± 1.59% and 13.72 ± 3.89% in the control, negative control GFP and 14-3-3epsilon-GFP groups, respectively. The percentages of the apoptotic cells were 0.84 ± 0.25%, 1.08 ± 0.24% and 2.93 ± 0.13% in the control, negative control GFP and 14-3-3epsilon-GFP groups, respectively. The numbers of cells that penetrated the filter membrane in the control, negative control GFP and 14-3-3epsilon-GFP groups were 20.65 ± 1.94, 17.63 ± 1.04 and 9.1 ± 0.24, respectively, indicating significant differences among the different groups.</p> <p>Conclusions</p> <p>Decreased expression of <it>14-3-3epsilon </it>in LSCC tissues contributes to the initiation and progression of LSCC. <it>14-3-3epsilon </it>can promote apoptosis and inhibit the invasiveness of LSCC.</p