Morphometric analysis in ethnic neonates from multiple substance exposure.

In the United States, approximately 10% of newborn infants are exposed prenatally to alcohol and/or illicit substances. However, no studies have evaluated the compounding effects of multiple illicit substances exposure in utero as potential teratogen (s). The potential teratogenic effects of nicotine and illicit substances (e.g. cocaine, marijuana and heroin) have previously been studied but there has been no documentation of facial landmark dislocation (s). Our goal is to investigate whether morphometric analysis could differentiate facial landmark dislocations in neonates of African descent, when exposed to alcohol, nicotine and illicit substances, either singly or in combination. Craniofacial features from a cohort of 493 African-American neonates less than 48 hours of age were analyzed by Multivariate Hotelling's T2 analysis of 99 relevant facial landmark triangles. Morphometric analysis discriminated unique asymmetries in groups of certain illicit exposure(s). Neonates with multiple prenatal exposures had fewer facial landmark dislocation(s) compared to single exposures. Deviation from normal facial features has the potential to be used as a screening tool for prenatal exposure to some illicit substances.

Apoptotic Effects of Novel Dithiocarbamate Analogs of Emetine in Prostate Cancer Cell Lines.

BACKGROUND/AIM: Prostate cancer is one of the leading causes of death in American males. Emetine, a naturally-derived alkaloid from the Ipecacuanha plant, has been shown to have potential for anti-tumorigenic effects for cancer treatments. The objective of this study was to characterize novel emetine dithiocarbamate (EMTDTC) analogs for potent anti-tumorigenic activity with minimal toxicity to normal prostate cells and identify targeted apoptotic regulatory genes. The leading key compounds, EMTDTC-55 and EMTDTC-56 were studied. MATERIALS AND METHODS: Established methods of cell flow cytometry were used to analyze apoptotic potential in prostate cancer cell lines (DU145, PC3 and LNCaP) and real time-polymerase chain reaction (PCR) for identifying key genes mediating apoptosis. RESULTS: The effect of EMTDTC-55 on DU145, LNCaP and PC3 revealed significant anti-tumorigenic activities. Both compounds showed highly significant apoptotic potential on days 3 and 5 in the prostate cancer cells. Key apoptotic genes were differentially regulated suggestive of cell-cycle arrest and apoptotic induction in androgen-independent cell lines, DU145 and PC3, by both compounds. However, in the androgen-dependent cell line LNCaP, cells were marginally affected by EMTDTC-55, but significant apoptosis was observed by EMTDTC-56 leading to cell-cycle arrest. CONCLUSION: Both dithiocarbamate compounds EMTDTC-55 and EMTDTC-56 have significant chemotherapeutic potential in moderately metastatic DU145 and highly metastatic PC3 cells.

Design, synthesis and cytotoxicity studies of dithiocarbamate ester derivatives of emetine in prostate cancer cell lines.

A small library of emetine dithiocarbamate ester derivatives were synthesized in 25-86% yield via derivatization of the N2'- position of emetine. Anticancer evaluation of these compounds in androgen receptor positive LNCaP and androgen receptor negative PC3 and DU145 prostate cancer cell lines revealed time dependent and dose-dependent cytotoxicity. With the exception of compound 4c, all the dithiocarbamate ester analogs in this study showed appreciable potency in all the prostate cancer cell lines (regardless of whether it is androgen receptor positive or negative) with a cytotoxicity IC50 value ranging from 1.312 ± 0.032 µM to 5.201 ± 0.125 µM by day 7 of treatment. Compared to the sodium dithiocarbamate salt 1, all the dithiocarbamate ester analogs (2 and 4a-4 g) displayed lower cytotoxicity than compound 1 (PC3, IC50 = 0.087 ± 0.005 µM; DU145, IC50 = 0.079 ± 0.003 µM and LNCaP, IC50 = 0.079 ± 0.003 µM) on day 7 of treatment. Consequently, it appears that S-alkylation of compound 1 leads to a more stable dithiocarbamate ester derivative that resulted in lower anticancer activity in the prostate cancer cell lines.