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A series of new, halogen containing N-substituted 4-aminobenzenesulfonamides were synthesized by using superacid HF/SbF5 chemistry and investigated as inhibitors of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, that is, the cytosolic hCA I and II and, the tumor-associated transmembrane isoforms hCA IX and XII. Despite the substitution of the sulfonamide function, the presence of fluorine atom(s) in β position of the sulfonamide function strongly favors hCA inhibition. A similar effect of the β-fluorinated alkyl substitution on the amino function has been also observed. Among the tested compounds, several chlorinated derivatives have been identified as selective nanomolar, tumor-associated isoforms inhibitors. These non-primary sulfonamides probably bind in the coumarin-binding site, at the entrance of the cavity, and not to the metal ion as the primary sulfonamide inhibitors., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Aqueous-ethanolic extract of Cassia alata (AECal) and its derived fractions obtained through liquid-liquid fractionation were evaluated for their bronchorelaxant, genotoxic, and antigenotoxic effects. Contractile activity of rats' tracheas in the presence of tested materials, as well as its modifications with different inhibitors and blockers, was isometrically recorded. The antigenotoxic potential of AECal was evaluated on cyclophosphamide- (CP-) induced genotoxicity in the rat. Animals were pretreated with the extract, then liver comet assay was performed. AECal and its chloroformic fractions (CF-AECal) relaxed the contraction induced by Ach, but both were significantly less potent in inhibiting contraction induced by KCl (30 mM; 80 mM). Propranolol, indomethacin, L-NAME, methylene blue, and glibenclamide did not modify the relaxant effect of CF-AECal. TEA altered the response of trachea to CF-AECal. CF-AECal caused a rightward shift without affecting the E max in cumulative concentration-response curves of Ach only at low concentrations. In animals pretreated with the extract, the percentage of CP-induced DNA damage decreased. Our results suggest that (1) muscarinic receptors contribute at least in part to the relaxant effects of CF-AECal; (2) CF-AECal interferes with membrane polarization; and (3) AECal is not genotoxic in vivo and contains chemopreventive phytoconstituents offering protection against CP-induced genotoxicity.

A series of benzofused sultams and fluorinated benzenesulfonamides were synthesized in superacid HF/SbF(5) from simple N-allylic derivatives. Almost all of these original compounds showed micromolar inhibitory activities against carbonic anhydrases I and II. The fluorinated derivatives inhibit better the tumor-associated isoforms IX and XII, and one of the tested compounds showed inhibition in the nanomolar range.

Background: Revision rhinoplasty for functional deformities can be both an aesthetic and reconstructive surgical challenge. We set out to quantify the health state utility assessment of living with the physical appearance of nasal asymmetry along with having nasal obstruction. The use of utility scores has helped to establish the health burden of living with various medical conditions. We sought to quantify living with a health state of nasal asymmetry with nasal obstruction after primary rhinoplasty using utility outcome scores., Methods: We used previously validated utility outcome measures to quantify the health burden of this clinical scenario in 128 prospective subjects. These subjects were from a sample of the population and medical students recruited to complete a survey to determine the utility outcome score of revision rhinoplasty using visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG) tests to obtain utility scores for revision rhinoplasty. Linear regression and Student t test were used for statistical analysis., Results: All measures (VAS, TTO, and SG) for functional nasal deformity (0.80±0.13, 0.90±0.12, and 0.91±0.13, respectively) of the 128 prospective subjects participating in this online study were significantly different (P<0.005) from the corresponding scores for monocular blindness (0.63±0.15, 0.85±0.16, and 0.85±0.19, respectively) and binocular blindness (0.38±0.18, 0.66±0.25, and 0.69±0.24, respectively). Being white was inversely related to the VAS utility scores for rhinoplasty (P<0.05). Additionally, female sex was positively correlated to the TTO score. Age, income, and education were not predictors of utility scores., Conclusions: In a sample of the population and medical students, VAS, TTO, and SG utility scores for revision rhinoplasty were determined and can be compared objectively with other health states and diseases with known utility scores. In a preoperative setting, women were objectively willing to potentially "trade" more years of life to treat a functional nasal deformity. If faced with a deformed nose after primary rhinoplasty, our sample population would consent to undergo a revision rhinoplasty procedure with a theoretical 9% chance of mortality and were willing to trade 3.6 years of their remaining life.

Background: Facial paralysis is a debilitating condition. Dynamic and static facial reanimation remains a challenge for plastic surgeons and requires important resources. Our objective was to quantify the health state utility assessment (ie, utility score outcomes) of living with unilateral facial paralysis., Methods: Utility assessments using visual analog scale, time trade-off, and standard gamble were used to obtain utility outcome scores for unilateral facial paralysis from a prospective sample of the general population and medical students., Results: A total number of 123 individuals prospectively participated in the study. All measures (visual analog scale, time trade-off, and standard gamble) for unilateral facial paralysis [0.56±0.18, 0.78±0.21, and 0.79±0.21 respectively] were significantly different (P<0.0001) from the corresponding outcome scores for monocular blindness [0.61±0.21, 0.83±0.21, and 0.85±0.18, respectively] and binocular blindness [0.33±0.18, 0.65±0.28, and 0.65±0.29, respectively]. Linear regression analysis using age, race, income, and education as predictors of each of the utility scores for facial paralysis showed no statistical significance., Conclusions: In samples of the general population and medical students, all utility score outcome measures for facial paralysis were lower than those for monocular blindness. Our sample population, if faced with unilateral facial paralysis, would theoretically undergo facial reanimation procedures with a willingness to sacrifice 8 years of life and be willing to undergo a procedure with a 21% chance of mortality to attain perfect health, respectively.

Background: Cleft lip and/or palate is a debilitating condition if left unrepaired, resulting in significant speech, hearing, swallowing, feeding, and psychosocial impairments. The authors' objective was to determine the potential impact of being born with cleft lip and/or palate by using previously validated health state utility assessment measures., Methods: A utility assessment using the visual analogue scale, time trade-off, and standard gamble was used to obtain utilities for cleft lip and/or palate, monocular blindness, and binocular blindness from a prospective sample of the general population and medical students. Average utility scores were compared using paired t test. Linear regression was performed using age, race, and education as independent predictors of each of the utility scores., Results: Over a 1-year prospective enrollment period, 110 participants were included in our utility analysis. The utility outcome scores for cleft lip and/or palate (visual analogue scale, time trade-off, and standard gamble, 0.69±0.18, 0.85±016, and 0.84±0.18, respectively) were statistically different from those of binocular blindness (visual analogue scale, time trade-off, and standard gamble: 0.38±0.17, 0.70±0.24, and 0.66±0.25, respectively; p<0.001) but not statistically different from those of monocular blindness (visual analogue scale, time trade-off, and standard gamble, 0.67±0.15, 0.86±0.15, and 0.84±0.18, respectively). There was no statistically significant difference in utility scores between male and female participants., Conclusion: The results of the study demonstrate objectively via health state utility scores that the perceived burden of being born with cleft lip and/or palate is comparable to living with monocular blindness.

Anti-Markovnikov additions to non-conjugated unsaturated amines in superacid are reported. In situ NMR studies, DFT calculations and labelled substrates reactions support the involvement of new ammonium-carbenium superelectrophiles in this original process.

α-Fluoroenamides, potent rigid fluorinated bioisosters of ureas, have been synthesized by a highly regio- and stereo-selective hydrofluorination of ynamides in anhydrous HF. This reaction provides the first general entry to α-fluoroenamides and can easily be applied to a wide range of substrates., (This journal is © The Royal Society of Chemistry 2012)

Herein, we show that after polyprotonation, superacid HF-SbF(5) is able to selectively depolymerise cellulose to water-soluble carbohydrates with 68 wt% yield of glucose. This process is efficient at low temperature, thus avoiding the formation of side products as commonly observed with conventional acids.

Background: The number of surgical procedures performed for obesity and massive weight loss (MWL) is increasing. The authors set out to quantify the health state utility assessment of living with MWL that can occur after such procedures., Methods: Utility assessments using the visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG) were used to obtain utilities for MWL, monocular blindness, and binocular blindness from a sample of the general population and medical students., Results: All the measures for MWL of the 100 volunteers (VAS, 0.79 ± 0.13; TTO, 0.89 ± 0.12; SG, 0.89 ± 0.15) were significantly different (p < 0.005) from the corresponding measures for monocular blindness (0.63 ± 0.18, 0.84 ± 0.17, and 0.86 ± 0.16, respectively) and binocular blindness (0.31 ± 0.17, 0.63 ± 0.28, and 0.66 ± 0.27, respectively) except for the SG utility measure comparing monocular blindness with MWL. Age was inversely proportional to the TTO utility scores for MWL (p < 0.05). Caucasian race and medical education were independent predictors of SG utility scores (p < 0.05)., Conclusion: In a sample of the general population and medical students, SG utility assessments for MWL were comparable with those for monocular blindness. Utility assessment of living with MWL varied with race (VAS and SG) and education (SG). The sample population, if faced with MWL, would consent to undergo a procedure such as body contouring with an 11% chance of death and be willing to trade 4 years of their life.

Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported. While two different pathways can be envisioned for the emergence of the transient secondary carbocationic intermediate, isotopic labeling experiments unambiguously revealed the involvement of a 1,2-hydride shift mechanism., (© 2011 American Chemical Society)

The first direct selective synthesis of novel gem-chlorofluorinated nitrogen-containing building blocks in superacid is reported. The dramatic role of the chlorine atom on the reaction is shown by in situ NMR experiments and allows the involvement of a novel original superelectrophilic activation process in superacid HF/SbF(5) to be postulated.

Background: There is not yet a consensus in defining the ability to breastfeed up to the recommended duration of 6 months after reduction mammaplasty. We reviewed the literature to study the possibility for successful and exclusive breastfeeding for this duration., Method: A systematic review of literature was performed using the Ovid Medline Database and the PubMed database to retrieve all published original articles that studied the effects of reduction mammaplasty on breastfeeding from 1950 to December 2008., Results: There appears to be no difference in breastfeeding capacity after reduction mammaplasty compared to women of the North American general population during the first month postpartum. Difficulties related to breastfeeding appear to be mostly explained by psychosocial issues related to advice and coaching received by healthcare workers during breastfeeding as well as other patient personal considerations., Conclusion: Women who have children after having had breast reduction surgery should be encouraged to breast feed. Consensus on the defining successful breastfeeding is required and we suggest using the definition of six months of exclusive breastfeeding as recommended by the WHO., (Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Controversy exists as to whether the benefits of facial transplantation outweigh the risk of continuous immunosuppression. Utility scores [range, 0 (death) to 1 (perfect health)] are a standardized tool with which to objectify health states or diseases and can help answer such controversy., Methods: An Internet-based utility assessment study using visual analogue scale, time trade-off, and standard gamble was used to obtain utilities for facial disfigurement requiring facial transplantation from a sample of the general population and medical students at McGill University. Average utility scores were compared using t test, and linear regression was performed using age, race, and education as independent predictors of each of the utility scores., Result: A total of 307 people participated in the study. All measures (visual analogue scale, time trade off, and standard gamble) for facial disfigurement (0.46 + or - 0.02, 0.68 + or - 0.03, and 0.66 + or - 0.03, respectively) were significantly different (p < 0.001) from the corresponding ones for monocular blindness (0.62 + or - 0.02, 0.83 + or - 0.02, and 0.82 + or - 0.02, respectively) and binocular blindness (0.33 + or - 0.02, 0.62 + or - 0.03, and 0.61 + or - 0.03, respectively). Age was inversely proportional to the utility scores in all groups (p < 0.01), decreasing a utility score of 0.006 for every increase in year of age., Conclusion: A sample of the general population and medical students, if faced with facial disfigurement, would undergo a face transplant procedure with a 34 percent chance of death and be willing to trade 12 years of their life to attain perfect health.

The synthesis of benzofused sultams and/or fluorinated sulfonamides, starting from N-allylic sulfonamides, was performed in superacid HF/SbF(5), through superelectrophilic activation. A dramatic effect of superacid composition on the selectivity of the reaction was shown and applied to the synthesis of cyclic 4-aminobenzenesulfonamides.

Background: Infantile hemangiomas represent one of the most common childhood tumors. The authors have previously demonstrated that the most appropriate management for such tumors is a nonoperative approach. Some authors have recently advocated surgical management as the primary treatment. Medical treatment such as steroids or interferon therapy has also been proposed. Definitive treatment for infantile parotid gland hemangioma remains controversial., Methods: In the retrospective study portion of this article, the authors reviewed the last 400 charts of children with hemangiomas managed at the Montreal Children's Hospital over the past 40 years. Twenty patients with parotid hemangiomas were identified. In the literature review portion, the Ovid MEDLINE and PubMed databases were used to retrieve all published original articles on the management of parotid hemangiomas from 1950 to December of 2008., Results: All of the authors' patients underwent successful nonoperative management, with 100 percent resolution of their parotid hemangiomas within 2 years of diagnosis, with an average follow-up time of 8.6 +/- 5.7 years. There were no complications of any of the treatments. The literature review retrieved a total of 413 patients in 12 original articles and four case reports. Management included observation and medical (steroid or interferon) and/or surgical treatment. Complications included failure to thrive, scarring, facial nerve palsy, and death., Conclusions: The authors have shown that nonoperative therapy resulted in regression and involution of infantile parotid hemangiomas with no major complications.

This paper describes the scope and limitations of the hydrofluorination reaction in superacid HF/SbF(5). On the basis of experimental studies of polyfunctional substrates' behaviour, the dramatic effect of substitution on the superelectrophilic character of ammonium-carbenium dications was emphasized. This reaction was applied to the synthesis of novel fluorinated key building blocks. Furthermore, the hydrofluorination reaction and the discovered homodimerization/fluorination reaction were applied to the synthesis of highly valued fluorinated diamines.

The novel cyclization/fluorination reaction of N-dienes in superacid was extended to substituted substrates. The influence of the substitution on superelectrophilic character of dicationic intermediates was shown and its dramatic effect on the synthesis of fluoropiperidines was studied. On the basis of new dicationic alpha-chloronium ammonium intermediates, starting from halogen-substituted dienes, high-valued fluorinated piperidines were synthesized.

Chemical genetic studies with enlarged ATP binding sites and unnatural ATP analogues have been applied to protein kinases for characterisation and substrate identification. Although this system is becoming widely used, there are limited data available about the kinetic profile of the modified system. Here we describe a detailed comparison of the wild-type cdk2 and the mutant gatekeeper kinase to assess the relative efficiencies of these kinases with ATP and unnatural ATP analogues. Our data demonstrate that mutation of the kinase alters neither the substrate specificity nor the phosphorylation site specificity. We find comparable K(M)/V(max) values for mutant cdk2 and wild-type kinase. Furthermore, F80G cdk2 is efficiently able to compensate for a defective cdk in a biological setting.

Various N,N-diallylic amines and amides were rapidly converted to fluorinated piperidines after a novel cyclisation/fluorination reaction in superacid HF-SbF5.

A range of unsaturated amines and sulfonamides were converted to beta-fluoro nitrogen analogues after hydrofluorination in superacid HF-SbF(5), based on the formation of highly reactive electrophilic intermediates.

Various allylic fluorides were prepared using a two-step process involving a cross-metathesis of allyltrimethylsilane with different olefinic partners followed by a fluorodesilylation of the corresponding functionalized allylsilanes with Selectfluor. [reaction: see text]