Synthesis of 13C-labeled parabens from isotopically enriched phenols using the Houben–Hoesch reaction

Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available ¹³C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding ¹³C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including ¹³C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing ¹³C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters.     

Effect of repeated exposures to nitrogen dioxide and sulfuric acid mist alone or in combination on mucociliary clearance from the lungs of rabbits

The biological response to ambient air pollution may be a function of specific combinations of pollutants. Groups of rabbits were exposed to NO2 (0.3 ppm or 1 ppm) with and without H2SO4 (0.5 mg/m3) for 2 hr/day for up to 14 days for assessment of effects upon mucociliary clearance of tracer particles from the tracheobronchial tree. Exposure to NO2 did not alter clearance, while exposure to H2SO4 produced a retardation toward the middle of the exposure series. The combination of 0.3 ppm NO2 with H2SO4 resulted in a speeding of clearance, while no change from control was seen with the mixture employing 1 ppm NO2 with acid. These results emphasize the importance of performing studies with pollutant mixtures, since it is not always possible to extrapolate responses from studies examining effects of individual pollutants.     

Correction to: Endovascular stroke treatment’s impact on malignant type of edema (ESTIMATE)

Journal of Neurology - The original keywords were not sufficiently precise in describing the article content. Therefore, the key words were amended to include hemicraniectomy and malignant edema.     

Weight Reduction after an Early Version of the Open Gastric Bypass for Morbid Obesity: Results after 23 Years

Background: While numerous promising short-term results of open gastric bypass for morbid obesity were published, the long-term outcome of earlier versions was somewhat disappointing. Thus, it was not until 1993 that this procedure was reintroduced with current modifications and now performed laparoscopically. Published long-term results of gastric bypass are still lacking. Methods: Out of an original population of 195 patients, we retrospectively analyzed the outcome of 98 patients (82 women, 16 men, mean age 32 years [range 17-54], mean weight 132 kg [range 65-200], mean BMI 46.6 kg/m²) operated on in Erlangen with mean follow-up 22.9 years (range 16.5-25.4). 3 different bariatric operations were performed: horizontal gastroplasty (HGP, n=18), stapled Roux-en-Y gastric bypass (S-RYGBP, n=14) and transected Roux-en-Y gastric bypass (T-RYGBP, n=66). BMI and percentage of excess weight loss (%EWL) were calculated at time 0, and after 1, 2, 3, 10, 15, 20 and 25 years. Results: Statistically significant weight loss was found for the whole patient population at every postoperative time-point compared to preoperative values. Maximal weight loss was achieved mainly during the first 3 years. However, initial and long-term outcome after HGP was significantly worse than after S-RYGBP or T-RYGBP. Gender did not significantly influence the results. Conclusion: Traditional open gastric bypass resulted in acceptable and safe long-term weight reduction. It may be assumed that laparoscopic gastric bypass with modern tiny pouch volumes based on the lesser curvature achieves even better and life-long weight reduction.     

MR-imaging pattern is not a predictor of occult atrial fibrillation in patients with cryptogenic stroke

Journal of Neurology - To date, insertable cardiac monitors (ICMs) are the most effective method for the detection of occult atrial fibrillation (AF) in cryptogenic stroke. The overall detection...     

Endovascular stroke treatment’s impact on malignant type of edema (ESTIMATE)

Journal of Neurology - In patients with acute ischemic stroke and large vessel occlusion, the prognosis has improved tremendously since the implementation of endovascular thrombectomy (EVT). The...     

Changes in early alveolar particle clearance due to single and repeated nitrogen dioxide exposures in the rabbit

To better understand the potential health risks associated with short-term NO2 exposures, a study was conducted to examine the effects of single and repeated NO2 exposures on the clearance of inert tracer particles from the alveolar region of rabbit lungs. Single 2-h exposures to 0.3, 1.0, 3.0, and 10.0 ppm produced a concentration-related acceleration in alveolar particle clearance, which resulted in greater particle removal when compared to control. The greatest response was produced at the lower NO2 levels, where as much as 40% more particles were cleared when compared to control. Fewer particles were cleared following a 10.0-ppm NO2 exposure when compared to the lower NO2 levels, and there were indications from the clearance pattern that the higher level was beginning to slow clearance, although an actual retardation was not found. Repeated 14-d exposures (2 h/d) to 1.0 or 10.0 ppm NO2 produced a response similar to a single exposure at the same concentration, suggesting a certain degree of adaptation was produced after the initial exposures. Possible mechanisms for these differences in clearance patterns are discussed. The results of this study demonstrated altered alveolar clearance following short-term NO2 exposure at environmentally relevant concentrations; changes in this important host defense mechanism may be indicative of some underlying pathologic condition.     

Plastic facial reconstruction in forensic medicine

Plastic facial reconstruction is the field of personal identification where the limitations of science are augmented by the intuition of an artist. In this field, success requires the cooperation of an anthropologist and a sculptor--and sometimes a little luck. Authors summarize the applications and limitations of this method. For the first time in the history of their institute, University Medical School of Pécs, the face of a victim in an actual crime case have been reconstructed. In this situation, the victim was in advanced stages of decomposition. The features of the man's face were unrecognizable. Using thirty craniometric measuring points, the soft tissues on the victims macerated scull was reconstructed, based on known soft tissue thickness of the middle-European population. After the reconstruction was complete, police circulated a photograph of the victim's face. The victim's son recognized her missing father from the photograph and notified the police. These efforts were noted as the first success of its kind in our region.     

Developmental toxicity evaluation of inhaled citral in Sprague-Dawley rats.

Citral is a commonly used fragrance and flavour ingredient that has demonstrated a potential for teratogenicity in chick embryo screening studies. To investigate potential mammalian developmental toxicity, pregnant Sprague-Dawley rats were exposed to citral by inhalation for 6 hr/day on gestation days 6-15 at mean concentrations of 0, 10 or 34 ppm as vapour, or 68 ppm as an aerosol/vapour mixture. Dams were killed on gestation day 20 and the foetuses were removed and evaluated for gross, visceral and skeletal malformations. Exposure to 68 ppm was maternally toxic, with reduced body-weight gains, ocular opacity, breathing difficulty, nasal discharge and salivation noted in the dams. No maternal toxicity was seen at the lower vapour exposure levels. The number of corpora lutea, implantations, resorptions, foetal viability, litter size, and sex ratio were not adversely affected by citral at any exposure level tested, and no exposure-related malformations were observed. At a maternally toxic exposure level, a slight reduction in mean foetal body weight and a slight increase in the incidence of hypoplastic bones were noted. Results of this study indicate that citral does not produce developmental toxicity in the rat when administered by inhalation at concentrations up to a maternally toxic exposure level.     

Acute and subchronic ozone inhalation in the rabbit: response of alveolar macrophages

Ozone is a potent oxidant gas and a common constituent of photochemical smog. This investigation evaluated the numbers and functional capabilities of alveolar macrophages (AM) recovered from rabbits undergoing acute and subchronic ozone exposure. Bronchoalveolar lavage was performed immediately, 24 h, and 7 d after acute (2-h) exposure to 0.1 or 1.2 ppm ozone, and on d 3, 7, and 14 during subchronic (2 h/d X 13 d) exposure to 0.1 ppm ozone. After acute exposure to 1.2 ppm, a marked increase in lavaged neutrophils was observed at 24 h. A single exposure to 0.1 ppm resulted in increased AM at 7 d, while repeated exposures resulted in an increase in AM and neutrophils on d 7 and 14. AM phagocytosis was depressed immediately and 24 h after acute exposure to 0.1 ppm, and at all time points after exposure to 1.2 ppm. Repeated exposures to 0.1 ppm produced reductions in the numbers of phagocytically active AM on d 3 and 7, with a return to control levels by d 14. Substrate attachment by AM was impaired immediately after exposure to 1.2 ppm; AM mobility was not altered by any of the ozone exposures. The results of these studies demonstrated significant alterations in the numbers and functional properties of AM as a result of single or repeated exposure to 0.1 ppm ozone, a level below the current National Ambient Air Quality Standard. These findings indicate that levels of ozone frequently encountered in areas of high photochemical air pollution can elicit a pulmonary inflammatory response and can impair pulmonary defense capabilities.