Significant Difference In Inhibitory Effect Research Articles

Efferent Inhibitory Effect Observed in Otoacoustic Emissions and Auditory Brainstem Response in the Neonatal Population

Objective: To characterize the inhibitory effect (IE) in the otoacoustic emission (OAE) and auditory brainstem response (ABR) in newborns at high and low risk for hearing loss. Design: Cross-sectional study. Patients and Methods: Seventy-nine newborns at low risk for hearing loss and 46 at high risk underwent transient evoked OAE (TEOAE), distortion product OAE (DPOAE) and ABR testing with or without the presence of contralateral white noise presented at a level of 60 dB SPL. Results: For both low- and high-risk newborns, there were no significant differences in IE between the left and right ears. There was a statistically significant difference in the right-ear IE between the low- and high-risk group for DPOAE and ABR testing. There was also greater agreement of the efferent system evaluation outcomes between TEOAE and ABR. Conclusions: ABR testing detected IE in a greater number of newborns in the low-risk, as compared to the high-risk group.

Abstract 2574: Curcumin either stimulates or inhibits expression of short isoform of stem-cell-marker DCLK1 (DCLK1-S) in non-transformed vs transformed cells, resulting in stabilization/inhibition of growth, respectively.

Abstract Inhibitory effects of curcumin are well documented on colon cancer cells, with minimal side effects on normal cells. Mechanisms mediating opposite effects of curcumin on normal vs cancer cells, remain unknown. We examined possible differential effects of curcumin on stem-cell-marker, DCLK1 in non-transformed (HEK-C, NCM460) vs transformed/cancer (HEKmGAS, HCT-116) cells. Curcumin (10-25μM) significantly inhibited growth of HEKmGAS/HCT-116 cells in a dose-dependent manner, with no significant effects on HEK-C cells. Surprisingly, transcript levels of DCLK1-S were increased by 3-10 fold in non-transformed cells, but decreased by 50-80% in transformed cells, which correlated with activation/inhibition of transiently transfected intron V promoter-reporter constructs in response to curcumin. Several cis elements, including NFκB binding sites, identified in intron V promoter, may play a role in transcribing DCLK1-S. Significant down-regulation of DCLK1-S by curcumin correlated with significant inhibition of NFκBp65 binding to intron V promoter in a ChIP assay. L-isoform of DCLK1 (DCLK1-L) was mainly expressed by non-transformed/normal cells, due to possible epigenetic silencing of DCLK1-L 5’promoter in cancer cells. The 5’ promoter was positive for several cis elements including TCF/β-catenin binding sites. Since Wnt/β-catenin pathway is up-regulated in many cancer cells, transiently transfected 5’ promoter-reporter constructs were activated by several fold in HEKmGAS/HCT-116 cells compared to that in non-transformed cells; curcumin significantly inhibited TCF expression and β-catenin binding to the 5’ promoter in a ChIP assay. However, since 5’ promoter is silenced in many cancer cells, significant effects of curcumin were not measured on DCLK1-L transcript in cancer cells. Curcumin did not inhibit DCLK1-L transcript in non-transformed cells, suggesting that pathways other than Wnt/β-catenin likely up-regulate DCLK1-L expression in normal cells, which may not be inhibited by curcumin. Role of other transcriptional factors in differential expression of S and L forms in non-transformed vs transformed cells remains unknown, which likely contributes to stimulatory vs inhibitory effects of curcumin on non-transformed vs transformed cells. It is speculated that significant differences in inhibitory effects of curcumin on transformed vs non-transformed cells may be due to significant differences in pathways inducing transcriptional activation of the promoters transcribing DCLK1-S/L isoforms. These differences may allow us to develop promoter-specific inhibitors for targeting cancer stem cells while sparing normal stem cells. This work was supported by NIH Grant to PS (R01CA09795909). Citation Format: Shubhashish Sarkar, Malaney O’ Connell1, Stephanie M. Moya, Pomila Singh. Curcumin either stimulates or inhibits expression of short isoform of stem-cell-marker DCLK1 (DCLK1-S) in non-transformed vs transformed cells, resulting in stabilization/inhibition of growth, respectively. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2574. doi:10.1158/1538-7445.AM2013-2574

Long term depression of human nociceptive skin senses induced by thin fibre stimulation

We have recently shown that stimulation, through a multi-electrode array, of thin nerve fibres close to the dermo-epidermal junction in the skin, produces powerful inhibition of itch and, to a lesser degree, cutaneous pain in humans. Here, we have studied the induction time and frequency dependency (range 1–10 Hz) of the inhibitory effects of such stimulation on itch, mechanical, and thermal pain, in 20 healthy subjects. Sixteen electrodes applied on the skin were consecutively stimulated using a method termed cutaneous field stimulation (CFS). The results show that different treatment periods with CFS were required for the induction of significant inhibitory effects on different nociceptive qualities: 1st heat pain (1 min), itch (3 min), 2nd heat pain (6 min), pinch evoked pain (8 min). Six to ten minutes stimulation sufficed to induce peak inhibitory effects on all these sensory qualities while longer stimulation (up to 40 min) did not cause significantly stronger inhibition. The effects on itch, 1st and 2nd heat pain lasted over 55 min after termination of CFS. There was no effect on prickle. No significant difference in inhibitory effects of different stimulation frequencies (1, 4 and 10 Hz/electrode) was found. The induction time and effective stimulation frequencies may suggest that the underlying mechanisms are similar to those of long term depression (LTD) previously described in the spinal cord in animal experiments.

Effects of diltiazem and verapamil on ADP-induced rabbit platelet shape change and aggregation

1. 1. The effects of diltiazem and verapamil (two structurally different calcium channel blockers) were examined on the rabbit platelets shape change and aggregation induced by adenosine-5′-diphosphate (ADP). 2. 2. ADP was a much more potent stimulator on inducing platelet shape change (ED 50 = 1 × 10 −7) than platelet aggregation (ED 50 = 1.78 × 10 −6). 3. 3. Both drugs similarly inhibited ADP-induced platelet shape change and aggregation at concentrations more than 300 μM. 4. 4. There were no significant differences in inhibitory effects of either diltiazem or verapamil on ADP-induced platelet shape change and aggregation. 5. 5. The inhibitory effects of diltiazem and verapamil on ADP-induced platelet shape change and aggregation at high concentrations may be due to their non specific properties.

一重項酸素による赤血球の溶血に対するフラン脂肪酸の抑制作用

As a continuation of the study on the biological roles of furan fatty acids (F acids) which are still vague, their inhibitory effects on the hemolysis of erythrocytes induced by singlet oxygen were examined. Hemolysis proceeded smoothly in the absence of F acids, but was suppressed significantly and dose dependently in their presence. No significant differences in inhibitory effects on the hemolysis induced by singlet oxygen between tetra-alkylsubstituted F acid (F3) and di-alkylsubstituted F acid (NMF) could be detected. The acids underwent oxidation to give the corresponding diketo-enes, indicating a reaction with singlet oxygen to suppress hemolysis. The inhibitory effects of F acids on hemolysis were compared with those of known singlet oxygen quenchers such as dimethylfuran, alpha-tocopherol, ascorbic acid and uric acid and F acids were found to be the most effective quenchers.

Antitumor effects of bacterial lipopolysaccharide and tumor necrosis factor in mice.

The effects of lipopolysaccharide (LPS) against tumor growth and on cellular immunity were studied in comparison with those of tumor necrosis factor (TNF). LPS and TNF, which were administered into mice with tumors, induced hemorrhagic necrosis within 48 hours after the initiation of the treatment. LPS and TNF significantly inhibited the tumor growth, as compared with findings in the controls. There was no significant difference in inhibitory effect on tumor growth between mice treated with LPS or TNF once or twice. Both LPS and TNF prevented the decrease of delayed type hypersensitivity in the tumor bearing mice.

LHRH and analogues as potential therapy for benign prostatic hyperplasia and hormone-dependent cancers.

In adult male rats, daily s.c. injections of 0.008-125 microgram luteinizing hormone releasing hormone (LHRH) or its analogue (D-Ala, des-Gly-NH2)LHRH ethylamide, led to significant differences in inhibitory effects on testicular function and accessory sex organ weights. The analogue was at least 35 times more potent than LHRH in reducing testicular LH/hCG receptors and 350 times more effective in decreasing plasma testosterone concentrations. In a second study, adult male rats treated with 25-2500 microgram LHRH daily for a 3-week period showed 85%-90% decrease in plasma testosterone concentrations. Treatment with 25 or 250 microgram LHRH effected a maximal 25% and 40% decrease of the ventral prostate and seminal vesicles, respectively, without affecting the testicular weight, the latter being reduced by 15% with the higher dose of 2500 microgram. The LHRH analogue is proposed for the treatment of prostatic and breast cancers while native LHRH could be an effective therapy for benign prostatic hyperplasia.