Metabolism of 3-Methyl-4-phenyl-3-butenamide

Abstract Urine of rabbits and rats treated with large doses of 3-methyl-4-phenyl-3-butenamide (I) was analyzed. Four metabolic products were isolated and identified: 2-hydroxy-3-methyl-4-phenyl-3-butenamide (II), 3-methyl-4-(4'-hydroxyphenyl)-3-butenamide (III), 3-benzyl-4-hydroxy-2-butenoic acid lactone (IV), and 3-(4'-hydroxybenzyl)-4-hydroxy-2-butenoic acid lactone (V). Compound IV was shown to be a metabolic intermediate between Compounds I and V. The metabolic fate of Compound I in man was found to be the same as in rat and rabbit

Ketalization of 3-Keto Group of 4-Pregnene-21-ol-3,20-dione and Syntheses of 21-Phenyl-4-pregnene-3,20-dione

20-Ketosteroids react with ethylene glycol in the presence of acids more quickly than the i4-3-keto group. It has been found that the i4-3-keto group of 4-pregnene-21-ol-3,20-dione (I) reacts with ethylene glycol in the presence of pyridine hydrochloriqe and anhydrous sodium sulfate more quickly than the 20-keto group. From the so obtained pregnene-21-ol-3,20-dione-3-ethyleneketal (IV) 21-phenyl-4-pregnene-3,20-dione (VII) was prepared

Thermal Ablation for Benign Thyroid Nodules: Radiofrequency and Laser

Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation

Mechanism of Hydroxylation of Steroids. Hydroxylation of 16a-Methyl-4-pregnene-21-ol-3,20- dione Acetate with Mucor Griseo-Cyanus

Mucor griseo-cyanus, which introduces an hydroxyl group in the 14-position of several steroids, converts 16a-methyl-4-pregnene- 21-ol-3,20-dione acetate (I) into a monohydrox:yderiva1Jive for which the structure 16a-methyl-4-pregnene-7a,21-diol-3,20-dione (III) has been determined. 16a-Methyl-4-pregnene-21-ol-3,20-dione acetate (I) and 16a- methyl-4-pregnene-7a,21-diol-3,20-dione (III) are transformed by Mucor griseo-cyanus, with a long time of incubation, into a dihydroxyderivative for which the structure 16a-methyl-4-pregnene- 7a,12~,21-triol-3,20-dione triacetate (VI) has been determined. The, 16a-methyl group in compound I inhibits the 14n-hydroxylase of Mucor griseo-cyanus by steric hindrance

Unusual presentation of thyrotoxicosis as complete heart block and renal failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Thyrotoxicosis is a clinical entity often very difficult to diagnose without biochemical confirmation as its clinical features can be highly varied. The most common cardiac manifestations of thyrotoxicosis are resting sinus tachycardia, supraventricular tachycardia including atrial fibrillation and atrial flutter with or without cardiac failure. Bradycardia and atrio-ventricular conduction defects are very uncommon in thyrotoxicosis.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old Caucasian man presenting with progressive weight loss, abnormal liver function, acute renal failure and complete heart block due to thyrotoxicosis.</p> <p>Conclusion</p> <p>Thyrotoxicosis should be considered as a possible diagnosis in patients with bradycardia and heart blocks associated with abnormal symptoms like weight loss. Nevertheless, the clinical, electrophysiological and biochemical abnormalities associated with thyrotoxicosis may be completely reversible restoring euthyroid state.</p

Multi-fiber distributed thermal profiling of minimally invasive thermal ablation with scattering-level multiplexing in MgO-doped fibers

[EN] We propose a setup for multiplexed distributed optical fiber sensors capable of resolving temperature distribution in thermo-therapies, with a spatial resolution of 2.5 mm over multiple fibers interrogated simultaneously. The setup is based on optical backscatter reflectometry (OBR) applied to optical fibers having backscattered power significantly larger than standard fibers (36.5 dB), obtained through MgO doping. The setup is based on a scattering-level multiplexing, which allows interrogating all the sensing fibers simultaneously, thanks to the fact that the backscattered power can be unambiguously associated to each fiber. The setup has been validated for the planar measurement of temperature profiles in ex vivo radiofrequency ablation, obtaining the measurement of temperature over a surface of 96 total points (4 fibers, 8 sensing points per cu). The spatial resolution obtained for the planar measurement allows extending distributed sensing to surface, or even three-dimensional, geometries performing temperature sensing in the tissue with millimeter resolution in multiple dimensions.The research has been supported by ORAU program at Nazarbayev University (grants LIFESTART 2017-2019 and FOSTHER2018-2020), by ANR project Nice-DREAM (grant ANR-14-CE07-0016-03), and by project DIMENSION TEC2017 88029-R funded by the Spanish Ministry of Economy and Competitiveness. This work was partly supported by the SIRASI project - Sistema Robotico a supporto della Riabilitazione di Arto Superiore e Inferiore (Bando INTESE - CUP: F86D15000050002).Beisenova, A.; Issatayeva, A.; Sovetov, S.; Korganbayev, S.; Jelbuldina, M.; Ashikbayeva, Z.; Blanc, W.... (2019). Multi-fiber distributed thermal profiling of minimally invasive thermal ablation with scattering-level multiplexing in MgO-doped fibers. Biomedical Optics Express. 10(3):1282-1296. https://doi.org/10.1364/BOE.10.001282S12821296103Goldberg, S. N., Gazelle, G. S., Compton, C. C., Mueller, P. R., & Tanabe, K. K. (2000). Treatment of intrahepatic malignancy with radiofrequency ablation. Cancer, 88(11), 2452-2463. doi:10.1002/1097-0142(20000601)88:113.0.co;2-3Padma, S., Martinie, J. B., & Iannitti, D. A. (2009). Liver tumor ablation: Percutaneous and open approaches. Journal of Surgical Oncology, 100(8), 619-634. doi:10.1002/jso.21364Sapareto, S. A., & Dewey, W. C. (1984). Thermal dose determination in cancer therapy. International Journal of Radiation Oncology*Biology*Physics, 10(6), 787-800. doi:10.1016/0360-3016(84)90379-1Shaw, A., ter Haar, G., Haller, J., & Wilkens, V. (2015). Towards a dosimetric framework for therapeutic ultrasound. International Journal of Hyperthermia, 31(2), 182-192. doi:10.3109/02656736.2014.997311Lubner, M. G., Brace, C. L., Hinshaw, J. L., & Lee, F. T. (2010). Microwave Tumor Ablation: Mechanism of Action, Clinical Results, and Devices. Journal of Vascular and Interventional Radiology, 21(8), S192-S203. doi:10.1016/j.jvir.2010.04.007Kennedy, J. E. (2005). High-intensity focused ultrasound in the treatment of solid tumours. Nature Reviews Cancer, 5(4), 321-327. doi:10.1038/nrc1591Yang, X. (2017). Science to Practice: Enhancing Photothermal Ablation of Colorectal Liver Metastases with Targeted Hybrid Nanoparticles. Radiology, 285(3), 699-701. doi:10.1148/radiol.2017170993Tosi, D., Schena, E., Molardi, C., & Korganbayev, S. (2018). Fiber optic sensors for sub-centimeter spatially resolved measurements: Review and biomedical applications. Optical Fiber Technology, 43, 6-19. doi:10.1016/j.yofte.2018.03.007Manns, F., Milne, P. J., Gonzalez-Cirre, X., Denham, D. B., Parel, J.-M., & Robinson, D. S. (1998). In Situ temperature measurements with thermocouple probes during laser interstitial thermotherapy (LITT): Quantification and correction of a measurement artifact. Lasers in Surgery and Medicine, 23(2), 94-103. doi:10.1002/(sici)1096-9101(1998)23:23.0.co;2-qSaccomandi, P., Schena, E., & Silvestri, S. (2013). Techniques for temperature monitoring during laser-induced thermotherapy: An overview. International Journal of Hyperthermia, 29(7), 609-619. doi:10.3109/02656736.2013.832411Froggatt, M. (1996). Distributed measurement of the complex modulation of a photoinduced Bragg grating in an optical fiber. Applied Optics, 35(25), 5162. doi:10.1364/ao.35.005162Macchi, E. G., Tosi, D., Braschi, G., Gallati, M., Cigada, A., Busca, G., & Lewis, E. (2014). Optical fiber sensors-based temperature distribution measurement inex vivoradiofrequency ablation with submillimeter resolution. Journal of Biomedical Optics, 19(11), 117004. doi:10.1117/1.jbo.19.11.117004Palumbo, G., Iadicicco, A., Tosi, D., Verze, P., Carlomagno, N., Tammaro, V., … Campopiano, S. (2016). Temperature profile of ex-vivo organs during radio frequency thermal ablation by fiber Bragg gratings. Journal of Biomedical Optics, 21(11), 117003. doi:10.1117/1.jbo.21.11.117003Parent, F., Loranger, S., Mandal, K. K., Iezzi, V. L., Lapointe, J., Boisvert, J.-S., … Kashyap, R. (2017). Enhancement of accuracy in shape sensing of surgical needles using optical frequency domain reflectometry in optical fibers. Biomedical Optics Express, 8(4), 2210. doi:10.1364/boe.8.002210MacChesney, J. B., O’Connor, P. B., & Presby, H. M. (1974). A new technique for the preparation of low-loss and graded-index optical fibers. Proceedings of the IEEE, 62(9), 1280-1281. doi:10.1109/proc.1974.9608Blanc, W., Mauroy, V., Nguyen, L., Shivakiran Bhaktha, B. N., Sebbah, P., Pal, B. P., & Dussardier, B. (2011). Fabrication of Rare Earth-Doped Transparent Glass Ceramic Optical Fibers by Modified Chemical Vapor Deposition. Journal of the American Ceramic Society, 94(8), 2315-2318. doi:10.1111/j.1551-2916.2011.04672.xBlanc, W., Guillermier, C., & Dussardier, B. (2012). Composition of nanoparticles in optical fibers by Secondary Ion Mass Spectrometry. Optical Materials Express, 2(11), 1504. doi:10.1364/ome.2.001504Todd, N., Diakite, M., Payne, A., & Parker, D. L. (2013). In vivo evaluation of multi-echo hybrid PRF/T1 approach for temperature monitoring during breast MR-guided focused ultrasound surgery treatments. Magnetic Resonance in Medicine, 72(3), 793-799. doi:10.1002/mrm.2497

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female Sprague‑Dawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E2) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.Fil: López Fontana, Constanza Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Sasso, Corina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Maselli, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Santiano, Flavia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Semino, Silvana Noemi. Universidad Nacional de Cuyo. Hospital Universitario. Laboratorio de Anatomía Patológica; Argentina;Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Caron, Ruben Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia