Massive Ameloblastoma Requiring Awake Nasal Fiberoptic Intubation.

Ameloblastomas are rare tumors that arises from the odontogenic epithelium. Although benign and slow growing, an extensive lesion may cause airway obstruction, making bag-mask ventilation and intubation a significant challenge. Here, we present a 54-year-old male in respiratory distress with an 18x15x13 cm submandibular mass causing airway compromise. The tumor was extensive, occupying most of the oral cavity. Unable to perform direct laryngoscopy because of the tumor burden, we performed an awake nasal fiberoptic intubation to secure the airway. Successful intubation was achieved as well as subsequently tracheostomy. We subsequently provide a discussion on associated challenges and management options for patients with ameloblastomas.

Fenoldopam Increases Urine Output in Oliguric Critically Ill Surgical Patients.

Background Fenoldopam is a short-acting dopamine A1 receptor agonist which mediates vasodilation of the renal arteries, thereby increasing urine output. The objective of this study was to compare the effects of fenoldopam and its synergistic effect on furosemide for improving the urine output in postoperative critically ill patients with acute kidney injury (AKI). Methods This is a retrospective study of postoperative critically ill patients with AKI. Patients who received furosemide (control group) were compared with those who received furosemide plus fenoldopam (treatment group) and evaluated at 12 and 24 hours post-treatment. Patients with oliguria and AKI were included in the study, while patients with chronic kidney disease (CKD) were excluded. Glomerular filtration rate, serum creatinine, blood pressure, calculated fluid accumulation, fluid intake, urine output, and total fluid output were used as variables to assess the medication effect. Results Of the 126 patients who met the inclusion and exclusion criteria, 87 patients received furosemide alone, and 39 patients received furosemide plus fenoldopam during their first 24 hours of admission to the surgical intensive care unit (SICU). Although not statistically significant, the addition of fenoldopam demonstrated an increase in mean urine output of 1525ml (IQR; 1530-2095) in the first 24 hours (P=0.06). There was also noted an increase in the urine output (p= 0.07) and a decrease in the total fluid accumulation when fenoldopam was co-administered with furosemide when compared to the patients who were only treated with furosemide (p=0.06). There was no significant change in creatinine clearance from baseline in either group.  Conclusion Fenoldopam may increase urine output in postoperative critically ill patients with acute kidney injury when administered within the first 24 hours of presentation. Based on our results, fenoldopam appears to have a synergistic effect with furosemide in our study population.

A Screening Method for Identification of Heterochromatin-Promoting Drugs Using Drosophila.

Drosophila is an excellent model organism that can be used to screen compounds that might be useful for cancer therapy. The method described here is a cost-effective in vivo method to identify heterochromatin-promoting compounds by using Drosophila. The Drosophila's DX1 strain, having a variegated eye color phenotype that reflects the extents of heterochromatin formation, thereby providing a tool for a heterochromatin-promoting drug screen. In this screening method, eye variegation is quantified based on the surface area of red pigmentation occupying parts of the eye and is scored on a scale from 1 to 5. The screening method is straightforward and sensitive and allows for testing compounds in vivo. Drug screening using this method provides a fast and inexpensive way for identifying heterochromatin-promoting drugs that could have beneficial effects in cancer therapeutics. Identifying compounds that promote the formation of heterochromatin could also lead to the discovery of epigenetic mechanisms of cancer development.

Streptonigrin at low concentration promotes heterochromatin formation.

Heterochromatin is essential for regulating global gene transcription and protecting genome stability, and may play a role in tumor suppression. Drugs promoting heterochromatin are potential cancer therapeutics but very few are known. In order to identify drugs that can promote heterochromatin, we used a cell-based method and screened NCI drug libraries consisting of oncology drugs and natural compounds. Since heterochromatin is originally defined as intensely stained chromatin in the nucleus, we estimated heterochromatin contents of cells treated with different drugs by quantifying the fluorescence intensity of nuclei stained with Hoechst DNA dye. We used HeLa cells and screened 231 FDA-approved oncology and natural substance drugs included in two NCI drug libraries representing a variety of chemical structures. Among these drugs, streptonigrin most prominently caused an increase in Hoechst-stained nuclear fluorescence intensity. We further show that streptonigrin treated cells exhibit compacted DNA foci in the nucleus that co-localize with Heterochromatin Protein 1 alpha (HP1α), and exhibit an increase in total levels of the heterochromatin mark, H3K9me3. Interestingly, we found that streptonigrin promotes heterochromatin at a concentration as low as one nanomolar, and at this concentration there were no detectable effects on cell proliferation or viability. Finally, in line with a previous report, we found that streptonigrin inhibits STAT3 phosphorylation, raising the possibility that non-canonical STAT function may contribute to the effects of streptonigrin on heterochromatin. These results suggest that, at low concentrations, streptonigrin may primarily enhance heterochromatin formation with little toxic effects on cells, and therefore might be a good candidate for epigenetic cancer therapy.

Identification of methotrexate as a heterochromatin-promoting drug.

Heterochromatin is a tightly packed form of DNA involved in gene silencing, chromosome segregation, and protection of genome stability. Heterochromatin is becoming more recognized in tumor suppression and may thus serve as a potential target for cancer therapy. However, to date there are no drugs that are well established to specifically promote heterochromatin formation. Here, we describe a screening method using Drosophila to identify small molecule compounds that promote heterochromatin formation, with the purpose of developing epigenetic cancer therapeutics. We took advantage of a Drosophila strain with a variegated eye color phenotype that is sensitive to heterochromatin levels, and screened a library of 97 FDA approved oncology drugs. This screen identified methotrexate as the most potent small molecule drug, among the 97 oncology drugs screened, in promoting heterochromatin formation. Interestingly, methotrexate has been identified as a JAK/STAT inhibitor in a functional screen, causing reduced phosphorylation of STAT proteins. These findings are in line with our previous observation that unphosphorylated STAT (uSTAT) promotes heterochromatin formation in both Drosophila and human cells and suppresses tumor growth in mouse xenografts. Thus, Drosophila with variegated eye color phenotypes could be an effective tool for screening heterochromatin-promoting compounds that could be candidates as cancer therapeutics.