Catalytic conversion of caffeine into molecules of valuable interest via N-demethylation reaction

This work aims to apply catalytic processes to promote the conversion of caffeine into valuable dimethylxanthines via N-demethylation reaction. Thus, we seek to evaluate the products formed and propose the reactions involved and their mechanisms. Reaction conditions were evaluated including different concentrations of Fenton reagent and ascorbic acid to evaluate caffeine oxidation. Theobromine, paraxanthine, and theophylline formation was proven by HPLC-DAD and mass spectrometry analysis evidencing the N-demethylation reactions, via radicals, with about 1 % yield. These results open the way for new N-demethylation reaction routes to be studied with applications for caffeine and other biomolecules in diverse areas such as biochemistry and medicinal chemistry. Application of the Fenton catalysis as alternative to promote the conversion of caffeine in other xanthines by N-demethylation. In this scenario was verified the capability of ascorbic acid in promoting same reaction, both environmentally friendly processes. This work investigates the possibility of using a well known biocompound as a precursor to obtain value added molecules.This study was financially supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 and by CIMO (UIDB/00690/2020) through FEDER under Program PT2020. In addition, the authors acknowledge Central de Análise e Prospecção Química – CAPQ and Laboratório Central de Biologia Molecular (LCBM), Chemistry Department/UFLA for their technical support. Jose L. Diaz De Tuesta acknowledges the financial support through the program of Atracción al Talento of Comunidad de Madrid (Spain) for the individual research grant 2022-T1/AMB-23946.info:eu-repo/semantics/publishedVersio

Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy

WSTĘP. Celem niniejszej pracy było porównanie skuteczności oraz bezpieczeństwa stosowania lamotryginy i amitryptyliny w opanowywaniu przewlekłego bólu spowodowanego obwodową neuropatią u chorych na cukrzycę. MATERIAŁ I METODY. Badanie kliniczne z randomizacją przeprowadzono w układzie naprzemiennym metodą podwójnie ślepej próby, z grupą kontrolną otrzymującą terapię standardową. W badaniu wzięły udział 53 osoby. Zastosowano różne dawki leków. Amitryptylinę stosowano w 3 dawkach doustnie: 10, 25 lub 50 mg, jednorazowo na noc przez 2 tygodnie, a lamotryginę - doustnie, 2 × na dobę, w 3 dawkach: 25, 50 lub 100 mg; każdą z dawek stosowano przez 2 tygodnie. Między zamianą leków zastosowano 2-tygodniową przerwę, podczas której chorzy otrzymywali placebo. Oceniano wpływ terapii na zmniejszenie bólu, ogólne polepszenie stanu zdrowia oraz wystąpienie działań niepożądanych. WYNIKI. W ogólnej ocenie pacjentów zniesienie bólu w dużym, umiarkowanym i małym stopniu zanotowano odpowiednio u 19 (41%), 6 (13%) i 7 (15%) osób przyjmujących lamotryginę oraz u 13 (28%), 5 (11%) i 15 (33%) osób stosujących amitryptylinę. Ogólna ocena przeprowadzona przez pacjentów i lekarzy, kwestionariusz McGilla i skala bólu Likerta nie wykazały różnic istotnych statystycznie. Poprawę obserwowano już po 2 tygodniach stosowania obu leków. Odnotowano 44 przypadki działań niepożądanych, 33 (75%) dotyczyły amitryptyliny, z czego najczęściej stwierdzano działanie nasenne (19 pacjentów, 43%); 11 przypadków (25%) dotyczyło lamotryginy, najczęściej była to wysypka (3 chorych, 7%) i podwyższenie stężenia kreatyniny (4 osoby, 9%). Preferowana dawka lamotryginy to 25 mg 2 × na dobę. WNIOSKI. Mimo że wykazano niewiele różnic w skuteczności obu leków, wybór lamotryginy w dawce 25 mg 2 × na dobę wydaje się lepszy, ze względu na mniejszą liczbę działań niepożądanych wywołanych w badanej populacji.AIMS. To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients. METHODS. A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out. RESULTS. Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient’s global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily. CONCLUSIONS. As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population

Kinetic insights on wet peroxide oxidation of caffeine using EDTA-functionalized low-cost catalysts prepared from compost generated in municipal solid waste treatment facilities

Nowadays, sorted organic fraction of municipal solid waste is typically treated by anaerobic digestion processes, resulting therein a solid stream, further processed to obtain compost, whose production is higher than the existing demand as fertilizer. The current work proposes an alternative strategy for the recovering of compost through the production of low-cost catalysts by calcination (1073 K) and sulfuric acid treatments, followed by sequential functionalization with tetraethyl orthosilicate (TEOS) and ethylenediamine tetraacetic acid (EDTA). Activity and stability of the catalysts are assessed in the wet peroxide oxidation of synthetic wastewater effluents contaminated with caffeine, a model micro-pollutant, achieving its complete removal after 6 h at 353– 383 K and catalyst loads of 0.5–2.5 g L−1. The increase of the catalytic activity of the materials upon functionalization with TEOS and EDTA is demonstrated and a kinetic modeling of caffeine degradation and hydrogen peroxide consumption with the best catalyst is assessed by pseudo-first power-law rate equations.This work was financially supported by project ‘‘VALORCOMP - Valorización de compost y otros desechos procedentes de la fracción orgánica de los residuos municipales’’, 0119_VALORCOMP_2_P, through FEDER under Program INTERREG; and CIMO (UIDB/00690/2020) through FEDER under Program PT2020.info:eu-repo/semantics/publishedVersio

Microstructural and mechanical study of AL2O3/Er3Al5O12 eutectic rods grown by the laser floating zone method

Eutectic rods of Al2O3–Er3Al5O12 were grown by directional solidification using the laser-heated floating zone method at rates in the range 25–1500 mm/h. Their microstructure and mechanical properties (hardness, toughness and strength) were investigated as a function of the growth rate. A homogeneous and interpenetrated microstructure was found in most cases, and interphase spacing decreased with growth rate following the Hunt–Jackson law. Hardness increased slightly as the interphase spacing decreased while toughness was low and independent of the microstructure. The rods presented very high bending strength as a result of the homogeneous microstructure, and their strength increased rapidly as the interphase spacing decreased, reaching a maximum of 2.7 GPa for the rods grown at 750 mm/h. The bending strength remained constant up to 1300 K and decreased above this temperature. The relationship between the microstructure and the mechanical properties was established from the analysis of the microstructure and of the fracture mechanism

Microestructura y propiedades mecánicas de fibras cerámicas eutécticas Al2O3/Er3Al5O12/ZrO2 procesadas por fusión zonal por láser.

Se han estudiado las fibras eutécticas Al2O3-Er3Al5O12-ZrO2 procesadas por fusión zonal por láser a distintas velocidades. Con el aumento de la velocidad de procesado se ha observado un refinamiento de la microestructura así como un cambio en la morfología de la misma. Se ha determinado mediante piezoespectroscopía que la fase alúmina se encuentra a compresión como consecuencia de las tensiones residuales que aparecen en la solidificación tras el fundido. El módulo de la componente hidrostática de dichas tensiones residuales se reduce conforme lo hace el tamaño de las fases. Se ha estudiado la dureza, la tenacidad de fractura y la resistencia a la flexión. Las dos primeras magnitudes han resultado independientes del tamaño de las fases, mientras que la resistencia a la flexión aumenta conforme disminuye el tamaño de las mismas. Finalmente, también se ha estudiado la dependencia de la resistencia a la flexión con la temperatura, observándose un comportamiento superplástico a 1700 K para la fibra procesada a mayor velocida

Application of catalysts developed from compost derived from municipal solid waste in the removal of caffeine by wet peroxide oxidation

Nowadays, waste management through mechanical biological treatment (MBT) consists on the use of the separated organic fraction of municipal solid waste (MSW) to feed anaerobic digestion processes, resulting therein a solid stream, further processed to compost, which can be used as fertilizer. Currently, the production of compost from MBT is higher than the existing demand, and the expected developments on up-coming directives ruling “End-of-waste” criteria are leading to barriers on the use of waste-derived fertilizers (European Commision, 2013). In this context, the current work proposes an alternative strategy to the valorisation of compost, through the production of low-cost materials to be applied in the catalytic wet peroxide oxidation (CWPO) of synthetic wastewater effluents contaminated with caffeine, used as a model pollutant of emerging concern. Caffeine is the most consumed psychoactive drug worldwide. It is one of the components of painkillers, medication against migraine, fatigue, drowsiness and breathing problems. Its consumption is also associated with an overall lower risk of malignant growth like hepatocellular, endometrial or colorectal cancer (Ganzenko et al., 2015). However, the effect of caffeine and its environmental degradation products on aquatic living species is not properly known. Caffeine, is a world wide consumed psychoactive drug, in a way that becomes a persistent compound and cannot be efficiently removed by municipal wastewater treatment facilities (Ganzenko et al., 2015). As a consequence, caffeine and its metabolites are present in the effluents of wastewater treatment plants (Gracia-Lor et al., 2017).This work was financially supported by project “VALORCOMP - Valorización de compost y otros desechos procedentes de la fracción orgánica de los residuos municipales”, 0119_VALORCOMP_2_P, and project “AIProcMat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, reference NORTE-01-0145-FEDER-000006, supported by NORTE 2020, under the Portugal 2020 Partnership Agreement, through FEDER, and Project Associate Laboratory LSRE-LCM - UID/EQU/50020/2019 - funded by national funds through FCT/MCTES (PIDDAC).info:eu-repo/semantics/publishedVersio

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements.RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.</p

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases

Profile of micronucleus frequencies and DNA damage in different species of fish in a eutrophic tropical lake

Lake Paranoá is a tropical reservoir for the City of Brasilia, which became eutrophic due to inadequate sewage treatment associated with intensive population growth. At present, two wastewater treatment plants are capable of processing up to 95% of the domestic sewage, thereby successfully reducing eutrophization. We evaluated both genotoxic and cytotoxic parameters in several fish species (Geophagus brasiliensis, Cichla temensis, Hoplias malabaricus, Astyanax bimaculatus lacustres, Oreochromis niloticus, Cyprinus carpio and Steindachnerina insculpita) by using the micronucleus (MN) test, the comet assay and nuclear abnormality assessment in peripheral erythrocytes. The highest frequencies of MN were found in Cichla temensis and Hoplias malabaricus, which were statistically significant when compared to the other species. However, Steindachnerina insculpita (a detritivorous and lake-floor feeder species) showed the highest index of DNA damage in the comet assay, followed by C. temensis (piscivorous). Nuclear abnormalities, such as binucleated, blebbed, lobed and notched cells, were used as evidence of cytotoxicity. Oreochromis niloticus followed by Hoplias malaricus, ominivorous/detritivotous and piscivorous species, respectively, presented the highest frequency of nuclear abnormalities, especially notched cells, while the herbivorous Astyanax bimaculatus lacustres showed the lowest frequency compared to the other species studied. Thus, for biomonitoring aquatic genotoxins under field conditions, the food web should also be considered