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1.
Chem Pharm Bull (Tokyo) ; 71(1): 74-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36596515

RESUMO

Propan-1,3-diol (PD) and propan-1,2-diol (propylene glycol, PG) are very similar compounds because their structures, safety data, and anti-microbial activities are almost the same. Actually, both compounds are made up of three carbon atoms and two hydroxyl groups. Regarding their safety, they do not have serious hazard data for animals, and LD50 values (in rats) of both are similar. As for the anti-microbial activity, minimum inhibitory concentration (MIC) values of both PD and PG are approximately 10% (v/v). In this study, we used the preservatives-effectiveness test (PET) to evaluate the anti-microbial activities of PD and PG, because both compounds are used in cosmetics as preservatives. The results indicated that PD was more effective as an anti-microbial agent compared with PG, and the effect of PD was marked against Escherichia coli and Pseudomonas aeruginosa. Scanning electron microscopy (SEM) images showed that the membrane of Escherichia coli was injured by PD and PG, but the damage by PD was more marked. The damage of the cell membrane may be the cause of high anti-microbial activity of PD in PET. These results suggest that PD has greater potential as a preservative, and PD should be recommended as an additive for food and medicine.


Assuntos
Anti-Infecciosos , Propilenoglicol , Animais , Ratos , Propilenoglicol/farmacologia , Anti-Infecciosos/farmacologia , Conservantes Farmacêuticos/farmacologia , Fenilpropanolamina/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana
2.
Molecules ; 27(12)2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35744906

RESUMO

Phenomena related to asymmetric amplification are considered to be key to understanding the emergence of homochirality in life. In asymmetric catalysis, theoretical and experimental models have been studied to understand such chiral amplification, in particular based on non-linear effects. Three decades after the theoretical demonstration that a chiral catalyst, when not enantiopure, could be more enantioselective than its enantiopure counterpart, we show here a new experimental example of nonlinear hyperpositive effect. We report here our investigations in the enantioselective zinc-catalyzed alkylation of benzaldehyde with N-pyrrolidinyl norephedrine as partially resolved chiral ligand, which shows a significant hyperpositive non-linear effect. A study of the underlying mechanism was conducted, which allows us to confirm a mechanism that implies a monomeric and a dimeric complex both catalyzing the reaction at a steady state and giving different enantioselectivities.


Assuntos
Compostos Organometálicos , Alquilação , Catálise , Fenilpropanolamina , Estereoisomerismo
3.
Int J Toxicol ; 41(5): 355-366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35658727

RESUMO

Cathine is the stable form of cathinone, the major active compound found in khat (Catha edulis Forsk) plant. Khat was found to inhibit major phase I drug metabolizing cytochrome P450 (CYP) enzyme activities in vitro and in vivo. With the upsurge of khat consumption and the potential use of cathine to combat obesity, efforts should be channelled into understanding potential cathine-drug interactions, which have been rather limited. The present study aimed to assess CYPs activity and inhibition by cathine in a high-throughput in vitro fluorescence-based enzyme assay and molecular docking analysis to identify how cathine interacts within various CYPs' active sites. The half maximal inhibitory concentration (IC50) values of cathine determined for CYP2A6 and CYP3A4 were 80 and 90 µM, while CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2 and CYP3A5 showed no significant inhibition. Furthermore, in Ki analysis, the Lineweaver-Burk plots depicted non-competitive mixed inhibition of cathine on both CYP2A6 and CYP3A4 with Ki value of 63 and 100 µM, respectively. Cathine showed negligible time-dependent inhibition on CYPs. Further, molecular docking studies showed that cathine was bound to CYP2A6 via hydrophobic, hydrogen and π-stacking interactions and formed hydrophobic and hydrogen bonds with active site residues in CYP3A4. Both molecular docking prediction and in vitro outcome are in agreement, granting more detailed insights for predicting CYPs metabolism besides the possible cathine-drug interactions. Cathine-drug interactions may occur with concomitant consumption of khat or cathine-containing products with medications metabolized by CYP2A6 and CYP3A4.


Assuntos
Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450 , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Ligantes , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Fenilpropanolamina
4.
Chembiochem ; 22(13): 2345-2350, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33880862

RESUMO

We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-ß-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.


Assuntos
Fenilpropanolamina/química , Estirenos/química , Alanina Desidrogenase/metabolismo , Álcool Desidrogenase/metabolismo , Álcoois/química , Biocatálise , Oxirredução , Fenilpropanolamina/metabolismo , Estereoisomerismo , Estirenos/metabolismo , Transaminases/metabolismo
5.
Molecules ; 26(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805790

RESUMO

A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.


Assuntos
Alcaloides/análise , Ephedra/química , Efedrina/análogos & derivados , Efedrina/análise , Ephedra/classificação , Estudos de Viabilidade , Humanos , Limite de Detecção , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Medicina Tradicional Chinesa , Fenilpropanolamina/análise , Preparações de Plantas/química , Pseudoefedrina/análise , Especificidade da Espécie
6.
Eur J Anaesthesiol ; 38(10): 1067-1076, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625060

RESUMO

BACKGROUND: In Germany, hypotension induced by spinal anaesthesia is commonly treated with a combination of cafedrine hydrochloride (C, 200 mg) and theodrenaline hydrochloride (T, 10 mg) in 2 ml. We compared the effectiveness of C/T with ephedrine. OBJECTIVES: The primary objectives were to assess the speed of onset and the ability to restore blood pressure without an increase in heart rate. Secondary objectives were to evaluate maternal/foetal outcomes and the number of required additional boluses or other additional measures. DESIGN: HYPOTENS was a national, multicentre, prospective, open-label, two-armed, noninterventional study comparing C/T with ephedrine in two prospectively defined cohorts. This study relates to the cohort of patients receiving spinal anaesthesia for caesarean section. SETTING: German hospitals using either C/T or ephedrine in their routine clinical practice. PATIENTS: Women aged at least 18 years receiving spinal anaesthesia for caesarean section. INTERVENTIONS: Bolus administration of C/T or ephedrine at the discretion of the attending anaesthesiologist. MAIN OUTCOME MEASURES: Endpoints within 15 min after initial administration of C/T or ephedrine were area under the curve between the observed SBP and the minimum target SBP; and incidence of newly occurring heart rate of at least 100 beats min-1. RESULTS: Although effective blood pressure stabilisation was achieved with both treatments, this effect was faster and more pronounced with C/T (P < 0.0001). The incidence of tachycardia and changes in heart rate were higher with ephedrine (P < 0.01). Fewer additional boluses (P < 0.01) were required with C/T. Although favourable neonatal outcomes were reported in both groups, base deficit and lactate values were greater with ephedrine (P < 0.01). Physician satisfaction was higher with C/T. CONCLUSIONS: After C/T, tachycardia was not a problem, providing an advantage over ephedrine. Fewer additional boluses were required with C/T, suggesting greater effectiveness. An increased base deficit with ephedrine suggests reduced oxygen supply or increased demands in foetal circulation. TRIALS REGISTRATION: Clinicaltrials.gov: NCT02893241, German Clinical Trials Register: DRKS00010740.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão Controlada , Hipotensão , Adolescente , Adulto , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Efedrina , Feminino , Humanos , Hipotensão/induzido quimicamente , Hipotensão/diagnóstico , Hipotensão/tratamento farmacológico , Recém-Nascido , Norepinefrina/análogos & derivados , Fenilpropanolamina/análogos & derivados , Gravidez , Estudos Prospectivos , Teofilina/análogos & derivados , Vasoconstritores/efeitos adversos
7.
J Emerg Med ; 60(4): 495-497, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33414048

RESUMO

BACKGROUND: Redotex™ is a Mexican weight-loss supplement that is not U.S. Food and Drug Administration-approved. It consists of the following five ingredients: tri-iodothyronine 75 µg, atropine 0.36 mg, diazepam 8 mg, aloin 16 mg, and d-norpseudoephedrine 50 mg per tablet. There are few case reports with clinically severe ingestions. We report two cases of clinical thyrotoxicosis due to use of Redotex. CASE REPORTS: A 29-year-old woman presented to the emergency department (ED) with anxiety and palpitations. She reported taking Redotex daily for 1 week. Her temperature was 37.1°C, blood pressure (BP) was 166/104 mm Hg, and heart rate (HR) was 140 beats/min. Laboratory analysis was significant for a bicarbonate level of 20 mmol/L (reference 22-29 mmol/L), free T4 0.75 ng/dL (reference 0.93-1.70 ng/dL), and thyroid-stimulating hormone (TSH) 0.05 uIU/mL (reference 0.27-4.20 uIU/mL). She was treated with 2 mg i.v. lorazepam and 20 mg oral propranolol. A 37-year-old woman presented with chest pain, palpitations, and nausea after taking Redotex 1 to 2 tablets daily for 6 weeks. Her HR was 134 beats/min and BP was 130/66 mm Hg. Thyroid function tests on initial presentation showed a TSH of 0.013 uU/mL, free T4 of 0.24 ng/dL, and free T3 of >30 pg/mL. She was treated with propranolol 1 mg i.v. twice per day and 2 doses of lorazepam 1 mg. Both patients had resolution of their symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When taken chronically and at recommended doses, Redotex can present with clinically significant T3 thyrotoxicosis. This has not been seen in prior reports.


Assuntos
Tireotoxicose , Redução de Peso , Adulto , Atropina , Diazepam , Combinação de Medicamentos , Ingestão de Alimentos , Emodina/análogos & derivados , Feminino , Humanos , Fenilpropanolamina , Tireotoxicose/induzido quimicamente , Tireotoxicose/diagnóstico , Tireotoxicose/tratamento farmacológico , Tri-Iodotironina
8.
Ann Ital Chir ; 92: 441-451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524119

RESUMO

OBJECTIVE: Pancreaticoduodenectomy has been established as the treatment of choice for the management of benign and malignant lesions of the pancreatic head, and pancreaticojejunal or pancreaticogastric anastomosis seems to be the safer choice for the management of the pancreatic duct. However, in certain seldom, but still existing circumstances, pancreatic duct ligation or occlusion with a chemical substance is a valuable and viable alternative. The aim of the current study is to compare these two methods of occlusion of the pancreatic duct regarding the endocrine and exocrine function of the pancreas and its histopathology. MATERIALS AND METHODS: 18 health mixed breed dog of both sexes were randomized in two groups: group A, in which the pancreatic duct was ligated and group B, in which the pancreatic duct was occluded with prolamine. RESULTS: None of the animals presented postoperatively steatorrhea and significant body weight changes. Peripancreatic inflammation at sacrifice, inflammatory cell infiltration and edema of the pancreas on the 15th postoperative day and 30th postoperative day were milder after occlusion with prolamine than after ligation. Ligation of pancreatic duct lead to significantly greater hyperamylasemia than prolamine occlusion every day until the 15th. Mild hyperglycemia presented from the first to the fourth day in both groups, which was associated with a significant drop in insulin. Glucagon remained within the normal values at all times during the experiment. None of glucose, insulin and glucagon differed between groups. CONCLUSION: Prolamine occlusion of the pancreatic duct causes milder hyperamylasemia and less extensive inflammation both macroscopically and microscopically than ligation. KEY WORDS: Pancreas, Pancreaticoduodenectomy, Hyperamylasemia.


Assuntos
Glucagon , Insulina , Amilases , Animais , Cães , Feminino , Glucose , Ligadura , Masculino , Pâncreas/cirurgia , Ductos Pancreáticos/cirurgia , Fenilpropanolamina
9.
Anaesthesist ; 70(4): 298-307, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33170310

RESUMO

BACKGROUND: Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally. METHODS: HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures. RESULTS: A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E. CONCLUSION: Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.


Assuntos
Raquianestesia , Hipotensão , Pressão Sanguínea , Efedrina/uso terapêutico , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Pessoa de Meia-Idade , Norepinefrina/análogos & derivados , Fenilpropanolamina/análogos & derivados , Estudos Prospectivos , Teofilina/análogos & derivados , Vasoconstritores/uso terapêutico
10.
Forensic Sci Int ; 319: 110658, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33370655

RESUMO

The consumption of Khat leaves represents an ancient kind of drug abuse mainly observed in Eastern Africa and the Arab Peninsula among adult men. For this purpose, the leaves are directly collected from the shrub "Catha edulis" prior to extensive chewing process. Seizures in Europe are rare, since the leaves have to undergo quick transportation: After a short period of time, the harvested leaves decompose and suffer in decrease of concentration of the active ingredient cathinone, which makes long term transportation difficult. As an alternative, plant material can be dried to increase life period. In the past years, an increasing number of seizures were made by Austrian police, however, the content of cathinone and cathine in dry material is widely unknown. In this work, a seizure of fresh Khat leaves was compared with two seizures of dried material in terms of concentration of cathinone and cathine using LC-MS/MS analysis. For fresh leaves, a purity grade was found to be 0.115-0.158% for cathinone and 0.172-0.192% for cathine, respectively. In contrast, subsequent storage of dried Khat leaves over months led to a dramatic loss of cathinone: Analysis of two seizures revealed that concentration of cathinone dropped to 0.021-0.023%. These findings are intended to serve as a guideline for Justice authorities to estimate the content of the controlled ingredients of Khat leaves in future.


Assuntos
Alcaloides/análise , Catha/química , Dessecação , Fenilpropanolamina/análise , Folhas de Planta/química , Cromatografia Líquida , Humanos , Transtornos Relacionados ao Uso de Substâncias , Espectrometria de Massas em Tandem
11.
J Enzyme Inhib Med Chem ; 36(1): 218-237, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33357002

RESUMO

A set of quinazolinones synthesized by the aid of L-norephedrine was assembled to generate novel analogues as potential anticancer and radiosensitizing agents. The new compounds were evaluated for their cytotoxic activity against MDA-MB-231, MCF-7, HepG-2, HCT-116 cancer cell lines and EGFR inhibitory activity. The most active compounds 5 and 6 were screened against MCF-10A normal cell line and displayed lower toxic effects. They proved their relative safety with high selectivity towards MDA-MB-231 breast cancer cell line. Measurement of the radiosensitizing activity for 5 and 6 revealed that they could sensitize the tumour cells after being exposed to a single dose of 8 Gy gamma radiation. Compound 5 was able to induce apoptosis and arrest the cell cycle at the G2-M phase. Molecular docking of 5 and 6 in the active site of EGFR was performed to gain insight into the binding interactions with the key amino acids.


Assuntos
Inibidores Enzimáticos/síntese química , Fenilpropanolamina/química , Quinazolinonas/síntese química , Radiossensibilizantes/síntese química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sítios de Ligação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/efeitos da radiação , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Receptores ErbB/metabolismo , Raios gama , Células HCT116 , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Simulação de Acoplamento Molecular , Fenilpropanolamina/metabolismo , Fenilpropanolamina/farmacologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Quinazolinonas/metabolismo , Quinazolinonas/farmacologia , Radiossensibilizantes/metabolismo , Radiossensibilizantes/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
12.
Brain Res ; 1748: 147098, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32896521

RESUMO

For over 50 years, the sympathomimetic phenylpropanolamine (PPA; ±-norephedrine) was a primary active ingredient in over-the-counter nasal decongestants for both children and adults and continues to be prevalent in the vast majority of countries today. Previously, we reported that juvenile PPA exposure alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC), impacting the motivational valence of cocaine in later life. The present study employed a combination of in vivo microdialysis and immunoblotting approaches to better understand how juvenile PPA exposure impacts catecholamine and glutamate function within the NAC. For this, C57BL/6J mice were pretreated repeatedly with PPA (0 or 40 mg/kg) during postnatal days 21-33. Starting at 70 days of age, the function and expression of receptors and transporters regulating extracellular dopamine and glutamate were determined. Juvenile PPA pretreatment completely abolished the capacity of selective dopamine and epinephrine reuptake inhibitors to increase NAC levels of both catecholamines, without impacting D2 or α2 receptor regulation of catecholamine release. Juvenile PPA pretreatment facilitated the rise in NAC glutamate elicited by dopamine, norepinephrine and glutamate transporter inhibitors and blunted mGlu2/3 inhibition of glutamate release in this region. These data confirm that juvenile exposure to PPA produces protracted perturbations in the regulation of extracellular catecholamine and glutamate levels within the NAC and further the hypothesis that early exposure to sympathomimetic drugs found in cough, cold and allergy medicines, have long-lasting effects upon neurotransmission within brain regions gating motivation.


Assuntos
Catecolaminas/metabolismo , Ácido Glutâmico/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Fenilpropanolamina/farmacologia , Simpatomiméticos/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Núcleo Accumbens/metabolismo
13.
J Chromatogr A ; 1623: 461176, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505280

RESUMO

A detailed computer simulation study of the isotachophoretic migration and separation of norpseudoephedrine stereoisomers for cases with the neutral selector added to the leader, immobilized to the capillary wall or support, or partially present in the separation column is presented. The electrophoretic transport of the analytes from the sampling compartment into the separation medium with the selector, the formation of a transient mixed zone, the separation dynamics of the stereoisomers with a free or immobilized selector, the dependence of the leader pH, the ionic mobility of norpseudoephedrine, the complexation constant and selector immobilization on steady-state plateau zone properties, and zone changes occurring during the transition from the chiral environment into a selector free leader are thereby visualized in a hitherto unexplored way. For the case with the selector dissolved in the leading electrolyte, simulation data are compared to those observed in experimental setups with coated fused-silica capillaries that feature minimized electroosmosis and zone detection with conductivity and absorbance detectors.


Assuntos
Isotacoforese , Fenilpropanolamina/química , Simulação por Computador , Eletro-Osmose , Fenilpropanolamina/análise , Fenilpropanolamina/isolamento & purificação , Dióxido de Silício/química , Estereoisomerismo
14.
Pharm Biol ; 58(1): 342-351, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32298156

RESUMO

Context: A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by restraint stress, while melatonin (MT) elicits anti-inflammation and antioxidant effects.Objective: The present study investigated the mechanisms of MT-mediated protection effects on restraint stress-induced GIMD.Materials and methods: 144 8-week-old male ICR mice were divided into four groups: control, restraint stress, restraint stress + MT and MT (positive control). 20 mg/kg MT or vehicle were intraperitoneally injected 60 min before restraint stress (10 h/day) once daily for 3 days. Biochemical parameters, intestinal mucosal integrity, tissues antioxidant ability and autophagic proteins levels were determined.Results: Mice subjected to restraint stress elevated NE level by 141.41% and decreased MT content by 38.82% in plasma. Consistent with the decrease in MT level, we observed a reduction in the antioxidant ability and an increase in autophagic proteins by 14.29-46.74% in the gut, resulting in injury to intestinal mucosa which was manifested by reductions in villus height and villus height/crypt depth (V/C) ratio, number of goblet and PCAN-positive cells, and expression of tight junction protein (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by restraint stress and improved the intestinal mucosal injury. However, there was no significant difference between MT (positive control) and control group.Discussion and conclusion: Our results suggest that MT effectively mitigates psychological stress-induced injury to intestinal mucosa, providing evidence demonstrating the potential for using MT as therapy against intestinal impairment associated with psychological stress.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Gastroenteropatias/tratamento farmacológico , Mucosa Intestinal/metabolismo , Melatonina/farmacologia , Estresse Psicológico/complicações , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Autofagia/efeitos dos fármacos , Gastroenteropatias/etiologia , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Melatonina/administração & dosagem , Melatonina/uso terapêutico , Camundongos , Camundongos Endogâmicos ICR , Fenilpropanolamina/metabolismo , Restrição Física , Proteínas de Junções Íntimas/metabolismo
15.
Endocrinology ; 160(10): 2314-2325, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504387

RESUMO

Adaptive thermogenesis is a catabolic process that consumes energy-storing molecules and expends that energy as heat in response to environmental changes. This process occurs primarily in brown and beige adipose tissue. Thermogenesis is regulated by many factors, including lipid derived paracrine and endocrine hormones called lipokines. Recently, technologic advances for identifying new lipid biomarkers of thermogenic activity have shed light on a diverse set of lipokines that act through different pathways to regulate energy expenditure. In this review, we highlight a few examples of lipokines that regulate thermogenesis. The biosynthesis, regulation, and effects of the thermogenic lipokines in several families are reviewed, including oloeylethanolamine, endocannabinoids, prostaglandin E2, and 12,13-diHOME. These thermogenic lipokines present potential therapeutic targets to combat states of excess energy storage, such as obesity and related metabolic disorders.


Assuntos
Adaptação Fisiológica/fisiologia , Benzofuranos/metabolismo , Cafeína/metabolismo , Di-Iodotironinas/metabolismo , Fenilpropanolamina/metabolismo , Termogênese/fisiologia , Ioimbina/metabolismo , Animais
16.
Plant Cell Physiol ; 60(10): 2193-2205, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31198964

RESUMO

Tudor-SN is involved in a myriad of transcriptional and post-transcriptional processes due to its modular structure consisting of 4 tandem SN domains (4SN module) and C-terminal Tsn module consisting of Tudor-partial SN domains. We had previously demonstrated that OsTudor-SN is a key player for transporting storage protein mRNAs to specific ER subdomains in developing rice endosperm. Here, we provide genetic evidence that this multifunctional RBP is required for storage protein expression, seed development and protein body formation. The rice EM1084 line, possessing a nonsynonymous mutation in the 4SN module (SN3 domain), exhibited a strong reduction in grain weight and storage protein accumulation, while a mutation in the Tudor domain (47M) or the loss of the Tsn module (43M) had much smaller effects. Immunoelectron microscopic analysis showed the presence of a new protein body type containing glutelin and prolamine inclusions in EM1084, while 43M and 47M exhibited structurally modified prolamine and glutelin protein bodies. Transcriptome analysis indicates that OsTudor-SN also functions in regulating gene expression of transcriptional factors and genes involved in developmental processes and stress responses as well as for storage proteins. Normal protein body formation, grain weight and expression of many genes were partially restored in EM1084 transgenic line complemented with wild-type OsTudor-SN gene. Overall, our study showed that OsTudor-SN possesses multiple functional properties in rice storage protein expression and seed development and that the 4SN and Tsn modules have unique roles in these processes.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Armazenamento de Sementes/metabolismo , Endosperma/genética , Endosperma/crescimento & desenvolvimento , Endosperma/fisiologia , Perfilação da Expressão Gênica , Glutens/metabolismo , Corpos de Inclusão/metabolismo , Mutação , Oryza/crescimento & desenvolvimento , Oryza/fisiologia , Fenilpropanolamina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Domínios Proteicos , Transporte de RNA , RNA de Plantas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Armazenamento de Sementes/genética
20.
Plant Physiol ; 179(3): 1111-1131, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659066

RESUMO

The transport and targeting of glutelin and prolamine mRNAs to distinct subdomains of the cortical endoplasmic reticulum is a model for mRNA localization in plants. This process requires a number of RNA-binding proteins (RBPs) that recognize and bind to mRNA cis-localization (zipcode) elements to form messenger ribonucleoprotein complexes, which then transport the RNAs to their destination sites at the cortical endoplasmic reticulum. Here, we present evidence that the rice (Oryza sativa) RNA-binding protein, RBP-L, like its interacting RBP-P partner, specifically binds to glutelin and prolamine zipcode RNA sequences and is required for proper mRNA localization in rice endosperm cells. A transfer DNA insertion in the 3' untranslated region resulted in reduced expression of the RBP-L gene to 10% to 25% of that in the wild-type. Reduced amounts of RBP-L caused partial mislocalization of glutelin and prolamine RNAs and conferred other general growth defects, including dwarfism, late flowering, and smaller seeds. Transcriptome analysis showed that RBP-L knockdown greatly affected the expression of prolamine family genes and several classes of transcription factors. Collectively, these results indicate that RBP-L, like RBP-P, is a key RBP involved in mRNA localization in rice endosperm cells. Moreover, distinct from RBP-P, RBP-L exhibits additional regulatory roles in development, either directly through its binding to corresponding RNAs or indirectly through its effect on transcription factors.


Assuntos
Retículo Endoplasmático/metabolismo , Oryza/metabolismo , Proteínas de Plantas/fisiologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/fisiologia , Transporte Biológico , Glutens/análise , Glutens/metabolismo , Oryza/genética , Fenilpropanolamina/análise , Fenilpropanolamina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Mensageiro/análise , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína
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