Birth defects after incestuous mating: Calculating the probability of causality and reflecting on the desirability of genetic testing

In this short communication we (1) show that, despite the rarity of autosomal recessive inheritance, primary congenital hydrocephalus in a girl stemming from father-daughter incest is most likely due to the incestuous union of her parents, and (2) reflect on the question, among others, whether actual genetic work-up to support victim indemnification is ever in the interest of the child.     

Response to Ozone in Volunteers with Chronic Obstructive Pulmonary Disease

Twenty-eight volunteers with chronic obstructive pulmonary disease were exposed to 0.0, 0.18, and 0.25 ppm ozone in purified air for 1-hr periods with light intermittent exercise, with exposure conditions presented in random order at 1-month intervals. No statistically significant changes attributable to ozone were found in forced expiratory performance or percent oxyhemoglobin (measured near the beginning and end of each exposure). No ozone-related changes in clinical status were found by interviews that included the time for 1 wk before to 1 wk after each exposure, except that a moderate increase in lower respiratory symptoms was reported by nonsmokers in 0.18 ppm exposures only. Thus, a slight decrement in hemoglobin saturation with ozone exposure (reported in two previous studies of chronic obstructive pulmonary disease subjects) may not be a common occurrence under typical ambient exposure conditions.     

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Epigenetic modifiers such as histone deacetylases (HDACs) have come into focus as novel drug targets for cancer therapy due to their functional role in tumor progression. Since common pan-HDAC inhibitors have adverse side effects and minor anti-cancer activity against solid tumors, enzyme-specific inhibitors were developed. HDAC6 is especially well-suited for specific inhibition due to its unique domain structure and mode of action and has been suggested to provide an exceptionally suitable target for cancer therapy. However, expression and function of HDACs have been insufficiently studied in urothelial cancers (UC), a disease urgently requiring new therapeutic approaches. The present study sought to evaluate HDAC6 as a target for treatment of urothelial cancers with enzyme-specific inhibitors. We observed moderate HDAC6 overexpression in urothelial cancer tissues and a broad range of expression in urothelial cancer cell lines. In the cell lines Tubacin was the most potent inhibitor, compared with Tubastatin and ST-80, but still active only at high micromolar concentrations. HDAC6 expression levels correlated poorly with sensitivity to enzyme inhibition. Combined treatments with heat shock, HSP90 inhibition by 17-AAG, proteasome inhibition by bortezomib, or DNA-damaging agents did not result in significant synergistic effects. Experiments with siRNA-mediated knockdown further underlined that urothelial cancer cells do not critically depend on HDAC6 expression for survival.     

Tactile Sensibility of Single‐Tooth Implants and Natural Teeth Under Local Anesthesia of the Natural Antagonistic Teeth

Introduction and Aim: The term osseoperception describes the capability of developing a subtle tactile sensibility over dental implants. The present clinical study aims at clarifying the question of how far tactile sensibility is to be attributed to the periodontium of the natural opposing tooth of the implant. Material and Method: Thirty‐two subjects with single‐tooth implants with natural opposing teeth were included in this clinical, single‐blind, split‐mouth study. The natural antagonistic tooth of the implant and the corresponding natural contralateral tooth were anesthetized with a locally infiltrated articaine anesthetic. In a computer‐assisted and randomized way, copper foils of varying thickness (0–100 µm) were placed interocclusally between the single‐tooth implant and the natural opposing tooth, and between the contralateral pair of natural opposing teeth in order to investigate the active tactile sensibility according to the psychophysical method of constant stimuli and evaluate it statistically by the Weibull distribution. Results: The average tactile sensibility of the implants with anesthetized antagonists at the 50% value calculated by means of the Weibull distribution was 20 ± 11 µm with a support area (90%–10% value) of 77 ± 89 µm. For the pair of natural teeth, the tactile sensibility at the 50% value was 16 ± 9 µm with a support area of 48.4 ± 93 µm. This resulted in an average intraindividual difference of 3.5 ± 7 µm at the 50% value and 29 ± 93 µm in the support area. The statistical calculations demonstrated an equivalent tactile sensibility (50% value) of the single‐tooth implant and the contralateral natural control tooth with the natural antagonists being anesthetized in each case (double t‐test, equivalence limit ± 8 µm, P < 0.01, power >80%). Conclusion: Apparently, the active tactile sensibility of single‐tooth implants with natural opposing teeth is not only to be attributed to the periodontium of the opposing tooth but also to a perception over the implant itself. This could support the hypothesis according to which the implant may have a tactile sensibility of its own.     

Butyrate Induces Glutathione S-Transferase in Human Colon Cells and Protects From Genetic Damage by 4-Hydroxy-2-Nonenal

Butyrate, one of the major products of gut fermentation, is known to inhibit proliferation, induce apoptosis and differentiation, and increase phase II enzyme activities in tumor cells, whereas little information is available on protective effects in less-transformed colon cells. The aim of this study was to investigate whether the chemoprotective mechanism of glutathione S-transferase (GST) induction by butyrate could also play a role in earlier stages of colon carcinogenesis and whether chemoresistance of cells toward the endogenous genotoxic risk factor 4-hydroxy-2-nonenal (HNE) could be a consequence of butyrate treatment. As cell models, we used the human tumor cell lines HT29 and HT29 clone 19A, a differentiated subclone with properties resembling primary colon cells. We determined the expression of GSTP1 protein (enzyme-linked immunosorbent assay), the major GST in HT29, GSTP1 mRNA (Northern blotting), GST activity, intracellular glutathione, and total protein. The genotoxic impact of HNE (100-200 μM) was compared in butyrate-treated and nontreated cells using single-cell microgel electrophoresis. Our results show that GSTP1 mRNA, GSTP1 protein, GST activity, and total protein were increased (1.2- to 2.5-fold) and glutathione levels were maintained after 24- 72 h of incubation with 4 mM butyrate. Moreover, a marked reduction of HNE-induced genotoxicity was caused by preincubation with butyrate. Butyrate also induced the phosphorylation of extracellular signal-regulated kinases (ERK1/2, Western blotting) after 5-30 min, which indicates a regulation of GST expression by this signal pathway. Most effects were greater in HT29 parent cells than in clone cells. In conclusion, butyrate enhances expression of GST and other proteins in both cell lines, which leads to an enhanced chemoprotection, reducing the impact of HNE genotoxicity. Thus butyrate could play a role in early and later stages of cancer prevention by reducing exposure to relevant risk factors.