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1.
Philos Trans R Soc Lond B Biol Sci ; 378(1871): 20220035, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36633276

RESUMO

Menaquinones (MKs) are electron carriers in bacterial respiratory chains. In Staphylococcus aureus (Sau), MKs are essential for aerobic and anaerobic respiration. As MKs are redox-active, their biosynthesis likely requires tight regulation to prevent disruption of cellular redox balance. We recently found that the Mycobacterium tuberculosis MenD, the first committed enzyme of the MK biosynthesis pathway, is allosterically inhibited by the downstream metabolite 1,4-dihydroxy-2-naphthoic acid (DHNA). To understand if this is a conserved mechanism in phylogenetically distant genera that also use MK, we investigated whether the Sau-MenD is allosterically inhibited by DHNA. Our results show that DHNA binds to and inhibits the SEPHCHC synthase activity of Sau-MenD enzymes. We identified residues in the DHNA binding pocket that are important for catalysis (Arg98, Lys283, Lys309) and inhibition (Arg98, Lys283). Furthermore, we showed that exogenous DHNA inhibits the growth of Sau, an effect that can be rescued by supplementing the growth medium with MK-4. Our results demonstrate that, despite a lack of strict conservation of the DHNA binding pocket between Mtb-MenD and Sau-MenD, feedback inhibition by DHNA is a conserved mechanism in Sau-MenD and hence the Sau MK biosynthesis pathway. These findings may have implications for the development of anti-staphylococcal agents targeting MK biosynthesis. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.


Assuntos
Naftalenos , Staphylococcus aureus , Vitamina K 2/farmacologia , Vitamina K 2/metabolismo , Staphylococcus aureus/metabolismo , Retroalimentação , Naftalenos/farmacologia
2.
Chempluschem ; 88(1): e202200449, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36680302

RESUMO

Herein is delineated a first systematic framework for the definition of structure-antioxidant property relationships in the dihydroxynaphthalene (DHN) series. The results obtained by a combined experimental and theoretical approach revealed that 1,8-DHN is the best performing antioxidant platform, with its unique hydrogen-bonded peri-hydroxylation pattern contributing to a fast H atom transfer process. Moreover, the comparative analysis of the antioxidant properties of DHNs carried out by performing DPPH and FRAP assays and laser flash photolysis experiments, revealed the higher antioxidant power associated with an α-substitution pattern (i. e. in 1,8- and 1,6-DHN) with respect to DHNs exhibiting a ß-substitution pattern (i. e. in 2,6- and 2,7-DHN). DFT calculations and isolation and characterization of the main oligomer intermediates formed during the oxidative polymerization of DHNs supported this evidence by providing unprecedented insight into the generation and fate of the intermediate naphthoxyl radicals, which emerged as the main factor governing the antioxidant activity of DHNs.


Assuntos
Antioxidantes , Naftalenos , Antioxidantes/química , Oxirredução
3.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674936

RESUMO

There is growing concern about the consumption of synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances, its consequence on human health (general population and workers), and the continuous placing of new SCs on the market. Although drug-induced alterations in neuronal function remain an essential component for theories of drug addiction, accumulating evidence indicates the important role of activated astrocytes, whose essential and pleiotropic role in brain physiology and pathology is well recognized. The study aims to clarify the mechanisms of neurotoxicity induced by one of the most potent SCs, named MAM-2201 (a naphthoyl-indole derivative), by applying a novel three-dimensional (3D) cell culture model, mimicking the physiological and biochemical properties of brain tissues better than traditional two-dimensional in vitro systems. Specifically, human astrocyte spheroids, generated from the D384 astrocyte cell line, were treated with different MAM-2201 concentrations (1-30 µM) and exposure times (24-48 h). MAM-2201 affected, in a concentration- and time-dependent manner, the cell growth and viability, size and morphological structure, E-cadherin and extracellular matrix, CB1-receptors, glial fibrillary acidic protein, and caspase-3/7 activity. The findings demonstrate MAM-2201-induced cytotoxicity to astrocyte spheroids, and support the use of this human 3D cell-based model as species-specific in vitro tool suitable for the evaluation of neurotoxicity induced by other SCs.


Assuntos
Astrócitos , Canabinoides , Humanos , Astrócitos/metabolismo , Canabinoides/toxicidade , Canabinoides/química , Naftalenos/toxicidade , Naftalenos/metabolismo , Neurônios/metabolismo
4.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674971

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Animais , Camundongos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Células 3T3-L1 , Adipogenia , Projetos Piloto , Naftalenos/farmacologia , Naftalenos/metabolismo , Tecido Adiposo/metabolismo , Poluentes Ambientais/metabolismo , Obesidade/metabolismo
5.
J Chromatogr A ; 1688: 463722, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36571981

RESUMO

Purification of basic drugs in reversed-phase mode is often difficult, mainly due to adsorption of positively charged compounds to the silica gel-based stationary phase. Since this adsorption can be suppressed under alkaline condition, columns with alkali-resistance are required. In addition, compounds with acid-sensitive structures are sometimes degraded during separation on silica gel-based columns which exhibit acidity due to their surface structure. We prepared an alkali-resistant reversed-phase packing material, Eggshell-PMAcO based on eggshells modified with an amphiphilic copolymer, poly(maleic acid-alt-1-octadecene) (PMAcO). The height equivalent to a theoretical plate (HETP) of the Eggshell-PMAcO column was improved by surface treatment with ammonium acetate buffer (900 mM, pH = 3.7), which is an inexpensive reagent, and the retention behavior for hydrophobic compounds was compared to a typical ODS column based on silica gel, resulting in sufficient selectivity of the eggshell-based column for hydrophobic compounds, as indicated by the ratio of retention factors of pentylbenzene and butylbenzene (Eggshell-PMAcO column: 1.55, ODS column: 1.65). Column temperature-dependent retention behavior of naphthalene was investigated in the temperature range from 25 °C to 45 °C, followed by the calculation of thermodynamic parameters. There was little difference in the standard molar enthalpy (Eggshell-PMAcO: -19.6 kJ/mol, ODS: -21.7 kJ/mol). The absolute value of the standard free Gibbs energy for the Eggshell-PMAcO column was much smaller than that of the ODS column (Eggshell-PMAcO: -0.284 kJ/mol, ODS: -13.0 kJ/mol), indicating that the Eggshell-PMAcO column had a weaker retention strength for naphthalene than the ODS column mainly due to the large difference in the standard molar entropy (Eggshell-PMAcO: -64.9 J/mol K, ODS column: -29.2 J/mol K). The retention capacities for imipramine under neutral (water/methanol) and alkaline (0.1% triethylamine water/methanol) conditions were 0.2 mg and 5 mg, respectively, based on injection mass-dependent HETP, retention factor and symmetry factor. Finally, the prepared column was applied to the purification of a building block for nucleic acid drugs. This study demonstrated that reversed-phase columns, which can be fabricated from eggshells and an amphiphilic copolymer in an inexpensive and eco-friendly way, have the ability to purify basic compounds and acid-sensitive compounds.


Assuntos
Casca de Ovo , Metanol , Animais , Cromatografia Líquida de Alta Pressão/métodos , Sílica Gel , Polímeros/química , Naftalenos , Água , Dióxido de Silício/química
6.
Sci Total Environ ; 862: 160845, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36526193

RESUMO

Coking industry has been considered as important source of volatile organic compounds (VOCs) emissions. However, few studies have emphasized the occurrence and adverse effects of VOCs from coking wastewater treatment processes. In this research, pollution profiles of both air and water phase VOCs in a typical coking wastewater treatment plant were investigated in terms of distribution characteristics, air-water exchange, ozone formation potential (OFP) and associated human health risks. Thirty VOCs were detected in the air phase, in which benzene and naphthalene were found to be the major VOCs with total contribution of 87.81 %. Nineteen VOCs were detected in the water phase, in which benzene, naphthalene and toluene contribute most to total VOCs with total contribution of 75.1 %. The regulating tank (RT) was the major source of VOCs, and the emission rate of total VOCs from all unites was 2711.03 g/d with annual emission of 0.99 t. The emission factor was estimated to be 1.36 g VOCs/m3 wastewater. The air-water exchange was assessed using the Fugacity model, and water-to-air volatilization was predominant based on the net flux of air-water exchange. OFP evaluated by emission factor indicated that the total OFP in RT was the highest (1.52 g O3/m3 wastewater), and toluene contributed 41.8 % of the total OFP, followed by naphthalene accounting for 38.7 % The total carcinogenic risks were in the range of 8.60 × 10-6 to 2.18 × 10-3, in which the RT exceeded the significant risk threshold (>1 × 10-4). The non-carcinogenic risks of hazard quotient value in RT also exceeded the risk threshold (>1), and naphthalene was the major contributor accounting for 79.02 %. These results not only provided comprehensive knowledge on pollution profiles and environmental risks of VOCs during coking wastewater treatment processes, but also facilitated the implement of VOCs regulation and occupational health protection strategies in coking industries.


Assuntos
Poluentes Atmosféricos , Coque , Ozônio , Compostos Orgânicos Voláteis , Purificação da Água , Humanos , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , Ozônio/análise , Benzeno , Monitoramento Ambiental/métodos , Medição de Risco , Naftalenos , Carcinógenos , Tolueno , China
7.
Environ Pollut ; 318: 120923, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36566676

RESUMO

Polycyclic aromatic hydrocarbons, a prominent family of persistent organic molecules produced by both anthropogenic and natural processes, are widespread in terrestrial and aquatic environments owing to their hydrophobicity, electrochemical stability and low aqueous solubility. Phenanthrene and naphthalene belong to the group of polycyclic aromatic hydrocarbons whose occurrence are reported to be relatively higher. The bioremediation mode of removing the toxicities of these two compounds has been reported to be promising than other methods. Most of the microbial classes of bacterial, fungal and algal origin are reported to degrade the target pollutants into non-toxic compounds effectively. The review aims to give an overview on toxicological studies, identification and enrichment techniques of phenanthrene and naphthalene degrading microbes and the bioremediation technologies (microbial assisted reactors, microbial fuel cells and microbial assisted constructed wetlands) reported by various researchers. All the three modes of bioremediation techniques were proved to be promising on different perspectives. In the treatment of phenanthrene, a maximum recovery of 96% and 98% was achieved in an aerobic membrane reactor with Bacillus species and single chamber air cathode microbial fuel cell with Acidovorax and Aquamicrobium respectively were reported. With the constructed wetland configuration, 95.5% of removal was attained with manganese oxide based microbial constructed wetland. The maximum degradation efficiency reported for naphthalene are 99% in a reverse membrane bioreactor, 98.5% in a marine sediment microbial fuel cell and 92.8% with a low-cost sandy soil constructed wetland.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Biodegradação Ambiental , Biotransformação , Naftalenos , Fenantrenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise
8.
Environ Pollut ; 318: 120919, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563993

RESUMO

Microplastics (MP) have received great attention due to the mass-produced residues discharged into the environment. MP are ideal for adhering to organic pollutants that can be easily dispersed, thus posing risks to human health. Furthermore, little has been reported on how different functional groups in polycyclic aromatic hydrocarbons (PAH) derivatives influence the adsorption behavior on MP. To better understand this process, groups methyl (-CH3) and hydroxyl (-OH) were selected and commercial and waste high-density polyethylene (HDPE, ≤ 1 mm) were used as adsorbents, and Naphthalene (Nap), 1-Methyl-Naphthalene (Me-Nap) and α-Naphthol as adsorbates. The results showed different behaviors for nonpolar and polar adsorbates. Dispersion forces were the main type of interaction between HDPE and Nap/Me-Nap, while dipole-induced dipole forces and H-bonding were the chief interactions involving MP and polar compounds. Regardless the HDPE source, Nap and Me-Nap have a Type III isotherm, and α-Naphthol presents a Type II isotherm. Nap and Me-Nap fitted to Freundlich isotherm of an unfavorable process (n = 2.12 and 1.11; 1.87 and 1.31, respectively), with positive values of ΔH° (50 and 77.17; 66 and 64.63 kJ mol-1) and ΔS° (0.070 and 0.0145; 0.122 and 0.103 kJ mol-1) for commercial and waste MP, respectively. Besides, the adsorption isotherm of α-Naphthol on commercial and waste HDPE fitted to the Langmuir model (Qmax = 42.5 and 27.2 µmol g-1, respectively), presenting negative values of ΔH° (-43.71 and -44.10 kJ mol-1) and ΔS° (-0.037 and -0.025 kJ mol-1). The adsorption kinetic study presents a nonlinear pseudo-second-order model for all cases. The K2 values follow the order Me-Nap > Nap > α-Naphthol in both MP. Therefore, this experimental study provides new insights into the affinity of PAH derivatives for a specific class of MP, helping to understand the environmental fate of residual MP and organic pollutants.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Humanos , Microplásticos/química , Plásticos , Polietileno , Adsorção , Poluentes Químicos da Água/análise , Naftalenos/química , Termodinâmica , Hidrocarbonetos Policíclicos Aromáticos/análise , Cinética , Concentração de Íons de Hidrogênio
9.
Arch Biochem Biophys ; 733: 109471, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36522814

RESUMO

NahE is a hydratase-aldolase that converts o-substituted trans-benzylidenepyruvates (H, OH, or CO2-) to benzaldehyde, salicylaldehyde, or 2-carboxybenzaldehyde, respectively, and pyruvate. The enzyme is in a bacterial degradative pathway for naphthalene, which is a toxic and persistent environmental contaminant. Sequence, crystallographic, and mutagenic analysis identified the enzyme as a member of the N-acetylneuraminate lyase (NAL) subgroup in the aldolase superfamily. As such, it has a conserved lysine (Lys183) and tyrosine (Tyr155), for Schiff base formation, as well as a GXXGE motif for binding of the pyruvoyl carboxylate group. A crystal structure of the selenomethionine derivative of NahE shows these active site elements along with nearby residues that might be involved in the mechanism and/or specificity. Mutations of five active site amino acids (Thr65, Trp128, Tyr155, Asn157, and Asn281) were constructed and kinetic parameters measured in order to assess the effect(s) on catalysis. The results show that the two Trp128 mutants (Phe and Tyr) have the least effect on catalysis, whereas amino acids with bulky side chains at Thr65 (Val) and Asn281 (Leu) have the greatest effect. Changing Tyr155 to Phe and Asn157 to Ala also hinders catalysis, and the effects fall in between these extremes. These observations are put into a structural context using a crystal structure of the Schiff base of the reaction intermediate. Trapping experiments with substrate, Na(CN)BH3, and wild type enzyme and selected mutants mostly paralleled the kinetic analysis, and identified two salicylaldehyde-modified lysines: the active site lysine (Lys183) and one outside the active site (Lys279). The latter could be responsible for the observed inhibition of NahE by salicylaldehyde. Together, the results provide new insights into the NahE-catalyzed reaction.


Assuntos
Frutose-Bifosfato Aldolase , Bases de Schiff , Frutose-Bifosfato Aldolase/genética , Cinética , Bases de Schiff/química , Bases de Schiff/metabolismo , Lisina , Mutagênicos , Sítios de Ligação , Aldeído Liases/química , Catálise , Hidrolases/metabolismo , Naftalenos , Especificidade por Substrato
10.
J Environ Sci (China) ; 126: 742-753, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36503799

RESUMO

The activated sludge process is characterized by high microbial density and diversity, both of which facilitate antibiotic resistance gene transfer. Many studies have suggested that antibiotic and non-antibiotic drugs at sub-inhibitory concentrations are major inducers of conjugative gene transfer. The self-transmissible plasmid pND6-2 is one of the endogenous plasmids harbored in Pseudomonas putida ND6, which can trigger the transfer of another co-occurring naphthalene-degrading plasmid pND6-1. Therefore, to illustrate the potential influence of stimulants on conjugative transfer of pND6-2, we evaluated the effects of four antibiotics (ampicillin, gentamycin, kanamycin, and tetracycline) and naphthalene, on the conjugal transfer efficiency of pND6-2 by filter-mating experiment. Our findings demonstrated that all stimulants within an optimal dose promoted conjugative transfer of pND6-2 from Pseudomonas putida GKND6 to P. putida KT2440, with tetracycline being the most effective (100 µg/L and 10 µg/L), as it enhanced pND6-2-mediated intra-genera transfer by approximately one hundred-fold. Subsequently, seven AS reactors were constructed with the addition of donors and different stimulants to further elucidate the conjugative behavior of pND6-2 in natural environment. The stimulants positively affected the conjugal process of pND6-2, while donors reshaped the host abundance in the sludge. This was likely because stimulant addition enhanced the expression levels of conjugation transfer-related genes. Furthermore, Blastocatella and Chitinimonas were identified as the potential receptors of plasmid pND6-2, which was not affected by donor types. These findings demonstrate the positive role of sub-inhibitory stimulant treatment on pND6-2 conjugal transfer and the function of donors in re-shaping the host spectrum of pND6-2.


Assuntos
Transferência Genética Horizontal , Esgotos , Naftalenos , Tetraciclina , Antibacterianos
11.
Food Res Int ; 162(Pt A): 111911, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461180

RESUMO

This study investigated the formation of polycyclic aromatic hydrocarbons (PAHs) in a mutton intramuscular fat model system containing epicatechin under various reaction conditions using multivariate statistical analysis, and established the optimal equations for PAHs prediction. Results indicated that at 100-180 °C for 10-60 min, epicatechin inhibited the formation of naphthalene, acenaphthylene, phenanthrene, anthracene, benz[a]anthracene and benzo[g,h,i]perylene by 10-37 %, 11-32 %, 9-100 %, 27-56 %, 100 % and 6-18 %, respectively. Polynomial equation third-order model with R2 at 0.87-0.98 and R2 at 0.80-0.95 well fitted for the formation of PAHs under various temperatures and times, respectively. The correlation coefficients of calibration set (R2c) and validation set (R2v) were 0.92 and 0.81 for naphthalene, 0.84 and 0.84 for acenaphthylene, 0.99 and 0.98 for phenanthrene, 0.97 and 0.95 for anthracene, 0.91 and 0.80 for benzo[g,h,i]perylene, respectively, which suggested good mathematical models for the PAHs formation rules. These results provide theoretical support to develop technologies for PAHs real-time monitoring during roasted mutton processing.


Assuntos
Catequina , Perileno , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Naftalenos , Antracenos
12.
Molecules ; 27(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36557897

RESUMO

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a-e and 7a-e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a-e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal-Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a-e and 7a-e were evaluated. Compounds 4a-e and 7a-e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids.


Assuntos
Antineoplásicos , Quinolonas , Estrutura Molecular , Receptores ErbB/metabolismo , Proliferação de Células , Quinolonas/farmacologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Antineoplásicos/química , Naftalenos/farmacologia , Naftalenos/química , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais
13.
PLoS One ; 17(12): e0279078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36512619

RESUMO

The dosage of evocalcet required to control serum parathyroid hormone (PTH) levels varies among secondary hyperparathyroidism (SHPT) patients. This post hoc analysis evaluated the dose-dependent efficacy of evocalcet on serum intact PTH (iPTH) levels, corrected calcium (Ca) and phosphate (P) levels, and safety, in an evaluation period (week 28 to week 30) by stratifying the previous phase 3 data with the final evocalcet dosages (low 1-2 mg [131 patients], medium 3-4 mg [90 patients], high 5-8 mg [92 patients]), and identified pre-treatment patient characteristics predicting the use of higher final evocalcet dosages via univariate and multivariate logistic regression models. At the end of the study at week 30, the median serum iPTH level was higher and the achievement ratio for the target range of Japanese Society for Dialysis Therapy (60-240 pg/mL) was lower in the final high-dose subgroup (216 pg/mL and 58%, respectively) than in the other subgroups (low: 149 pg/mL and 79%; medium: 149 pg/mL and 73%, respectively). Among the three subgroups, the mean serum corrected Ca and P levels demonstrated similar trends, and similar ratio of patients achieved the target range (corrected Ca, 8.4-10 mg/dL; P, 3.5-6.0 mg/dL) from week 28 to week 30. No dose-dependent safety concerns were identified. Younger age, prior cinacalcet use, higher serum levels of iPTH and corrected Ca, procollagen type 1 N-terminal propeptide, intact fibroblast growth factor-23, and larger maximum parathyroid gland volume were significantly associated with final high-dose evocalcet (p < 0.05 in all cases). Patients requiring final high-dose evocalcet had pre-treatment characteristics indicating severe SHPT, leading to a lower final achievement rate for the target PTH levels of Japanese Society for Dialysis Therapy. Therefore, the early initiation of evocalcet treatment for SHPT is critical. Trial registration: This trial was registered as follows: ClinicalTrials.gov: NCT02549391 and JAPIC: JapicCTI-153013.


Assuntos
Hiperparatireoidismo Secundário , Humanos , Cálcio , Cinacalcete/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Naftalenos/uso terapêutico , Hormônio Paratireóideo , Diálise Renal
14.
BMC Psychiatry ; 22(1): 723, 2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403047

RESUMO

BACKGROUND: Inhalant or volatile substance use is a health issue with significant medical and psychiatric sequelae. Inhalants or volatile substances are volatile organic substances found in domestic and commercial products which are inhaled to obtain pleasurable effects. They are easily accessible, cheap, and legal. Common inhalants are spray, paints, glue and shoe polish whilst naphthalene or 'mothball' abuse is reported less commonly. We report a case of a 29-year-old female who inhaled and ingested naphthalene during her pregnancy. This case report is unique because the dependence on naphthalene was confined to pregnancy and resolved as soon as she delivered. This brings up the question whether pregnancy in general increases the risk of substance dependence in vulnerable populations or whether the dependence in this patient during pregnancy is due to individual factors. CASE PRESENTATION: The patient we report is a 29-year-old female who developed a strong desire to inhale mothballs during her third pregnancy. The pattern of use started in the first trimester meeting the criteria for dependence syndrome and resolved completely by the second day following delivery. She had features suggestive of harmful use in her second pregnancy as well. CONCLUSIONS: The case report emphasizes that pregnant women should be screened for psychoactive substance use. Equally important is the need for adequate psychoeducation about the myths and cultural beliefs associated with pregnancy-related cravings and the potentially devastating consequences of harmful cravings on the neonate and the mother. The case highlights how chemicals used in day-to-day activities can lead to dependence.


Assuntos
Odorantes , Transtornos Relacionados ao Uso de Substâncias , Recém-Nascido , Humanos , Feminino , Gravidez , Adulto , Naftalenos/efeitos adversos , Fissura
15.
J Org Chem ; 87(23): 15947-15962, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36378998

RESUMO

A divergent strategy for natural polyketides synthesis has been designed. This synthetic route allowed chemical alterations leading to all stereoisomers of the natural agropyrenol 1, sordarial 2, and heterocornol B 4. Key steps involve desymmetrization of divinylcarbinol using asymmetric Sharpless epoxidation and Heck coupling of an easily available aromatic partner and prepared chiral alkene. The versatility of the synthetic method was demonstrated on the preparation of heterocornol A 3 and sordariol 5. The absolute and relative configurations of prepared natural compounds 2·1/3C6H12 and 4 were confirmed and assigned by single-crystal X-ray analysis.


Assuntos
Naftalenos , Estereoisomerismo
16.
Psychopharmacology (Berl) ; 239(12): 3953-3962, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36344824

RESUMO

OBJECTIVE: Lifelong premature ejaculation (PE) is regarded as one of the most common male sexual dysfunction. We aimed to detect whether insula-related brain functional networks are altered in lifelong PE patients and whether such alterations are "normalised" after selective serotonin reuptake inhibitors (SSRI) administration. METHODS: Twenty-three drug-naive lifelong PE patients and 30 healthy controls (HC) were recruited in current study. All subjects underwent resting-state functional magnetic resonance imaging (fMRI) scan at first. One hour after dapoxetine administration, all patients underwent fMRI scanning again. The degree centrality (DC), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analysis, and ROI-based functional connectivity (FC) analysis were applied to calculate the abnormalities in insula-related functions among three groups. RESULTS: Compared to HC group, PE patients at baseline showed significantly altered DC, ALFF, and ReHo value of the bilateral insula, which subsequently showed a "normalised" trend after dapoxetine administration. Additionally, compared to HC group, PE patients at baseline showed significantly decreased FC between insula and precentral gyrus, inferior frontal gyrus, middle/inferior temporal gyrus, and caudate, while patients after dapoxetine administration showed increased insula-related FC in anterior cingulate cortex and decreased FC in thalamus and middle/inferior temporal gyrus. The main effects of dapoxetine were located in precentral gyrus, inferior frontal gyrus, caudate, and limbic system. CONCLUSIONS: Our findings report altered brain mechanism of insula in lifelong PE patients and also indicate that dapoxetine can "normalise" the abnormal function of the insula to certain extent in lifelong PE patients.


Assuntos
Ejaculação Precoce , Humanos , Masculino , Ejaculação Precoce/diagnóstico por imagem , Ejaculação Precoce/tratamento farmacológico , Benzilaminas/farmacologia , Naftalenos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem
17.
Bioresour Technol ; 366: 128210, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36323372

RESUMO

In this study, the metabolic fates and response strategies of microorganisms to aromatic compounds with different structures (phenol, naphthalene, phenanthrene, and pyrene) were comparatively studied. The results indicated that the phenol (90.9%), naphthalene (68.4%), phenanthrene (69.5%), and pyrene (67.1%) could be mineralized, and the biotoxicity also has been drastically reduced. The degradation characteristics and toxic effects were closely related to their chemical structure. The microorganisms showed different response strategies to aromatic compounds with different structures. Phenol had a simple structure and low toxicity, the microbial community structure was simple, and the rapid expression of key enzymes enabled it to be rapidly degraded. For the hydrophobic and complex naphthalene, phenanthrene, and pyrene, the more complex the structure, the higher the microbial diversity, the EPS showed different response for the purpose of improving their bioavailability, and the activity of key enzymes was positively correlated with their structural complexity.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Biodegradação Ambiental , Pirenos , Fenantrenos/metabolismo , Compostos Orgânicos , Naftalenos , Fenol
18.
Sci Rep ; 12(1): 20527, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443410

RESUMO

Pollution of the environment by crude oil and oil products (represented by various types of compounds, mainly aliphatic, mono- and polyaromatic hydrocarbons) poses a global problem. The strain Pseudomonas veronii 7-41 can grow on medium-chain n-alkanes (C8-C12) and polycyclic aromatic hydrocarbons such as naphthalene. We performed a genetic analysis and physiological/biochemical characterization of strain 7-41 cultivated in a mineral medium with decane, naphthalene or a mixture of the hydrocarbons. The genes responsible for the degradation of alkanes and PAHs are on the IncP-7 conjugative plasmid and are organized into the alk and nah operons typical of pseudomonads. A natural plasmid carrying functional operons for the degradation of two different classes of hydrocarbons was first described. In monosubstrate systems, 28.4% and 68.8% of decane and naphthalene, respectively, were biodegraded by the late stationary growth phase. In a bisubstrate system, these parameters were 25.4% and 20.8% by the end of the exponential growth phase. Then the biodegradation stopped, and the bacterial culture started dying due to the accumulation of salicylate (naphthalene-degradation metabolite), which is toxic in high concentrations. The activity of the salicylate oxidation enzymes was below the detection limit. These results indicate that the presence of decane and a high concentration of salicylate lead to impairment of hydrocarbon degradation by the strain.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Alcanos , Naftalenos , Biodegradação Ambiental , Salicilatos
19.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362092

RESUMO

Charge transport in crystalline organic semiconductors (OSCs) is considerably hindered by low-frequency vibrations introducing dynamic disorder in the charge transfer integrals. Recently, we have shown that the contributions of various vibrational modes to the dynamic disorder correlate with their Raman intensities and suggested a Raman-based approach for estimation of the dynamic disorder and search for potentially high-mobility OSCs. In the present paper, we showcase this approach by revealing the highest-mobility OSC(s) in two series of crystalline naphthalene diimide derivatives bearing alkyl or cycloalkyl substituents. In contrast to our previous studies, Raman spectra are not measured, but are instead calculated using periodic DFT. As a result, an OSC with a potentially high charge mobility is revealed in each of the two series, and further mobility calculations corroborate this choice. Namely, for the naphthalene diimide derivatives with butyl and cyclopentyl substituents, the estimated room-temperature isotropic electron mobilities are as high as 6 and 15 cm2 V-1 s-1, respectively, in the latter case even exceeding 20 cm2 V-1 s-1 in a two-dimensional plane. Thus, our results highlight the potential of using the calculated Raman spectra to search for high-mobility crystalline OSCs and reveal two promising OSCs, which were previously overlooked.


Assuntos
Imidas , Análise Espectral Raman , Imidas/química , Naftalenos , Vibração
20.
Eur J Dermatol ; 32(4): 445-450, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36301750

RESUMO

Acne vulgaris is typically treated with a combination of a topical retinoid plus an antimicrobial agent, as recommended by national and international evidence-based guidelines around the globe. Adapalene, a synthetic topical retinoid, is available in two concentrations (0.1% and 0.3%) and in once-daily fixed-dose combinations with benzoyl peroxide (BPO) 2.5%. Adapalene 0.3%/BPO 2.5% is approved for use for moderate-to-severe acne with proven efficacy, good safety and tolerability across a spectrum of patient variables (different ages, genders, and skin types) and disease severity. While some patients experience issues with transient tolerability during retinoid and BPO therapy, it is our clinical experience that good patient education to set expectations and provide strategies to minimize irritation can overcome the majority of issues. This article reviews the data supporting the use of adapalene 0.3%/2.5% in practice, including the complementary mechanism of action of adapalene and BPO, clinical data from a range of settings, and key aspects of patient education.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Humanos , Feminino , Masculino , Adapaleno , Fármacos Dermatológicos/efeitos adversos , Naftalenos/uso terapêutico , Combinação de Medicamentos , Géis/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Acne Vulgar/tratamento farmacológico , Retinoides/uso terapêutico , Resultado do Tratamento
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