Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies

1. A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer.

2. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use.

3. In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ER?+?human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling studies.

4. In biological activity assays monochloro substituted indole hydrazones were found to have stronger aromatase inhibitory activity among all tested derivatives and were more active than melatonin. This finding is further confirmed by molecular modelling.

5. These results may be useful in the design and synthesis of novel melatonin analogues with higher inhibitory potency against aromatase.

     

Alverine citrate induced acute hepatitis

Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity.     

How does parental smoking affect nasal mucociliary clearance in children?

European Archives of Oto-Rhino-Laryngology - Correlation between passive smoking and nasal mucociliary clearance (MCC) in pediatric population has not been reported before. Therefore, in this...     

Evaluation of the corpus callosum shape in patients with obstructive sleep apnea

Sleep and Breathing - The aim of this study was to examine whether or not there was a difference in corpus callosum shape between patients with mild to moderate and severe obstructive sleep apnea...     

Dexmedetomidine–ketamine and midazolam–ketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: a randomized prospective study

Purpose

Extracorporeal shock wave lithotripsy (ESWL) requires sedation in pediatric patients. Dexmedetomidine is a relatively new agent used for sedation. The aim of this randomized prospective study was to compare the effects of dexmedetomidine–ketamine and midazolam–ketamine combinations on the recovery time, hemodynamic and respiratory variables, and side effects in pediatric patients undergoing ESWL.

Methods

Fifty pediatric patients aged between 2 and 15 years who were scheduled for elective ESWL were randomized into two groups. In Group D we applied dexmedetomidine at1 μg/kg, given over 10 min, and a bolus of 1 mg/kg ketamine for sedation. In Group M we applied midazolam at a 0.05 mg/kg bolus dose 10 min before the procedure and a 1 mg/kg bolus of ketamine. We measured and monitored the hemodynamic variables, oxygen saturation, and recovery time, and we also monitored the side effects.

Results

Four patients in group D refused to complete the study; 21 patients in group D and 25 patients in group M completed the study. We found the recovery time [eye-opening time (9.3 ± 4.5 vs. 16.2 ± 6.5 min; p < 0.001), verbal response time (12.8 ± 4.9 vs. 19.2 ± 7.2 min; p < 0.001), and the cooperation time (17.1 ± 5.0 vs. 23.3 ± 7.7 min; p < 0.001)] to be shorter in the dexmedetomidine group. Also, the heart rate values were lower in the dexmedetomidine group at the 20th minute of the procedure (99.1 ± 19.0 vs. 118.7 ± 7.3 beats/min; p = 0.016).

Conclusion

In this study we found the recovery time to be shorter, with hemodynamic stability, in the dexmedetomidine group, compared with the midazolam group. So we can conclude that dexmedetomidine may be a good and safe alternative agent for sedation, with a shorter recovery period than midazolam, in the pediatric population.

     

Modeling leaching behavior of solidified wastes using back-propagation neural networks

In a previous study, treatment sludge obtained from a chemical industry, which contained potentially toxic heavy metals and organics, was characterized and solidified by solidification/stabilization (S/S). In this study, however, the prediction of leaching behavior of the sludge by linear regression method and neural networks (NNs) was discussed. NN analysis was used to construct models of leaching behavior as a function of mix composition (waste/binder ratio, W/B) using existing data from the previous study of cement-based S/S. The differences in leaching rate of each metal were also considered. The hazard characteristics of the waste were determined as defined in both Turkish and US EPA regulations, by means of Extraction Procedure Toxicity Test (EPTox) and DIN 38414-S4 Test. S/S studies were conducted using Portland cement to solidify the sludge containing high amount of Cr, Cu, Hg, Ni, Pb, and Zn. The W/B ratios of 36 specimens were kept between 0/100 and 40/100. The specimens were cured at room temperature for 7, 28, and 90 days. The heavy metal content of the extracts of each specimen was detected usually less than standard concentrations in EPTox and DIN 38414-S4 leaching procedures. By the use of NN, leaching behavior of the solidified wastes can be predicted and, therefore, optimum S/S technologies can be achieved.     

Analysis and comparison of changing in thyroid hormones after percutaneous and surgical tracheotomy

Objectives

To evaluate the effect of the surgical and percutaneous tracheotomy on the thyroid hormones and their comparisons.

Materials and methods

Between January and May 2010, the surgical and percutaneous tracheotomy had been performed on 40 patients with respiration problems. The thyroid hormone levels were measured just before, after one and three hour of the operation and than these measurements were compared statistically.

Results

The effect of the surgical and percutaneous tracheotomy on serum thyroglobulin (TG), free thyroxine (fT4), free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) levels was found statistically significant.

Conclusions

The surgeons should not forget the possible increase of the serum thyroid hormone levels after the surgical and percutaneous tracheotomy because of the systemic effects of thyroid hormones. The patients, especially who have cardiac rhythm problems, should be monitored for a while after these processes because the increase of serum thyroid hormones may cause undesired cardiovascular effects.