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1.
Ital J Dermatol Venerol ; 157(6): 510-514, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36177779

RESUMO

BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from different cofactors. The alteration of the skin microbiome has recently been revealed to play a role in acne pathogenesis. Concerns with side effects of available systemic treatment for acne resulted in a greater focus on topical therapies, such as topical azelaic acid which showed to be an effective and safe treatment option for acne. The aim of our study was to evaluate the efficacy of a new treatment protocol for acne based on an oral supplement composed of biotin and 3 strains of lactic ferments combined with a topical gel composed of azelaic acid, hydroxypinacolone retinoate, and α-hydroxy acids. METHODS: An Italian single-center interventional study was performed enrolling patients suffering from mild-to-moderate-acne. Patients were treated with a supplement based on biotin and 3 strains of lactic ferments, combined with a topical gel product (azelaic-acid, hydroxypinacolone retinoate, and α-hydroxy acids). All enrolled patients were scheduled for a total of 2 visits, a baseline visit (V0) and a follow-up visit after 60 days of treatment (V1). RESULTS: A total of 30 patients were enrolled in the study. Between V0 (baseline) and V1 (60 days), there was a reduction of 37.4% in the GAGS Score, 40.7% in the SEBUTAPEtm Score, and 18% in the TEWL Score, and an increment of 44% in the T-Blue Test Score. No cases of serious AEs were reported in our experience. CONCLUSIONS: Our results confirmed the promising therapeutic role of a probiotic supplement associated with topical therapy in the treatment of mild to moderate acne.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Probióticos , Humanos , Fármacos Dermatológicos/efeitos adversos , Biotina/uso terapêutico , Acne Vulgar/tratamento farmacológico , Probióticos/uso terapêutico , Hidroxiácidos/uso terapêutico
2.
Bioresour Technol ; 355: 127304, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35562023

RESUMO

Aromatic and hydroxyl acid treatments demonstrate their respective characteristics for the separation of lignocellulosic biomass. In this study, the effect of salicylic acid (SA-A) treatment on the separation of eucalyptus components with both aromatic and hydroxyl acid properties was analyzed. The optimal conditions were SA-A concentration 9.0%, reaction temperature 140 °C and time 75 min. The separation yield of xylose was 85.93%. The separation of cellulose and lignin was inhibited by SA-A treatment in contrast to the separation by glycolic acid and p-toluenesulfonic acid treatment. Moreover, SA-A treatment resulted in a larger fiber crystallinity index and higher thermal stability. The SA-A-treated samples contained lignin that was rich in ß-O-4 and hydroxyl groups. The degradation and condensation of lignin was inhibited. The selectivity of aromatic acids for separating hemicellulose and protecting the lignin structure using hydroxy acids was demonstrated. Thus, new and efficient organic acid treatments can be developed.


Assuntos
Eucalyptus , Ácidos , Biomassa , Eucalyptus/química , Hidroxiácidos , Lignina/química , Polissacarídeos , Ácido Salicílico
3.
J Tradit Chin Med ; 42(2): 264-271, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35473348

RESUMO

OBJECTIVE: To assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K ß-hydroxy acid form (MKA), Heye (), and Cangzhu (), compared to lifestyle modifications. METHODS: Totally 117 subjects with moderate to severe dyslipidemia (according to Chinese guidelines) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of MKA, LM plus a high dosage of MKA, and treated for 60 d. The primary endpoint was the reduction of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Safeties along with Traditional Chinese Medicine Syndromes were assessed through the study. RESULTS: A low dosage of MKA along with lifestyle modifications caused a significant decrease in LDL-C by 15.6% on average (95% , 9.6% to 21%) with, a decrease in TC by 15.3% on average (95% CI, 9.26% to 21.4%), and a decrease in non-HDL-C by 35.4% (95% CI, 25.76% to 41.34%). Weak evidence of a reduction of triglycerides but an increment of HDL-C was observed in patients with severe hyperlipidemia. No severe adverse events occurred during the study. CONCLUSION: Our results confirm the LDL-C and TC lowering properties of MKA is clinically meaningful. It also produces a significant reduction of non-HDL-C, and slightly effects on TG and HDL-C as well.


Assuntos
Hipercolesterolemia , Hiperlipidemias , Produtos Biológicos , LDL-Colesterol , Humanos , Hidroxiácidos , Hipercolesterolemia/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Lovastatina/efeitos adversos
4.
Food Funct ; 13(9): 5124-5134, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35416190

RESUMO

The objective of the present study was to examine the effects of hydroxy citric acid (HCA) extracts from Garcinia cambogia on metabolic, atherogenic and inflammatory biomarkers in obese women with non-alcoholic fatty liver disease (NAFLD). The present clinical trial was carried out on 40 overweight/obese women with NAFLD. The patients were randomly allocated into either the "HCA group" (receiving calorie-restricted diet (-700 kcal d-1) accompanied by HCA tablets) and the "control group" (receiving only calorie-restricted diet) for eight weeks. Weight, height, body mass index (BMI), and waist circumference (WC) were measured. Fasting blood sugar (FBS), lipid profile, liver enzymes, as well as inflammatory biomarkers were determined at baseline and after the intervention. Dietary intake was assessed at baseline and at the end of the trial and food intake data were analyzed by the Nutritionist IV software. Results showed a decrease in energy and macronutrient intake in both groups (p < 0.05). Weight, BMI, WC, and hip circumference as well as FBS, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) decreased and high-density lipoprotein cholesterol (HDL-C) increased significantly in the HCA group (p < 0.05). There were also significant reductions in WC, FBS, TG, total cholesterol, LDL-C in the control group while inter-group changes in FBS, TG, LDL-C and HDL-C were statistically significant. Although atherogenic indices reduced significantly in both groups, inter-group comparison revealed that the HCA group showed greater decrease in the TG/HDL-C ratio than the control group (p = 0.004). Other atherogenic indices including TC/HDL-C and non-HDL-C/HDL-C ratio showed greater reduction in the control versus HCA group (p < 0.01). Some inflammatory factors were reduced in the HCA group; however, no significant within- or between-group differences were revealed post-intervention. Our results indicated that HCA supplementation plus calorie-restricted diet could improve some metabolic factors without any significant effect on inflammation in patients with NAFLD.


Assuntos
Aterosclerose , Hepatopatia Gordurosa não Alcoólica , Aterosclerose/tratamento farmacológico , Biomarcadores , Restrição Calórica , Colesterol , HDL-Colesterol , LDL-Colesterol , Ácido Cítrico , Suplementos Nutricionais , Feminino , Humanos , Hidroxiácidos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/tratamento farmacológico , Triglicerídeos
5.
Orthop Surg ; 14(4): 704-713, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35195339

RESUMO

OBJECTIVES: To evaluate the efficacy of resistance training (RT) combined with beta-hydroxy-beta-methylbutyric acid (HMB) in the treatment of elderly patients with sarcopenia after hip replacement. METHODS: From January 1, 2018 to December 31, 2018, 200 elderly patients (68 men, mean age 76.3 years and 137 women, mean age 79.1 years) who experienced femoral neck fracture with sarcopenia after hip arthroplasty were assigned to four groups: RT + HMB group, RT group, HMB group, and negative control group. Baseline data, body composition, grip strength, Barthel index (BI), Harris hip score (HHS), and visual analog scale score (VAS) were compared among the four groups before and 3 months after surgery. RESULTS: A total of 177 participants completed the trial, including 43 in the HMB + RT group, 44 in the HMB group, 45 in the RT group, and 45 in the negative control group. At the 3-month follow-up, the body composition and grip strength of the HMB + RT group and RT group were significantly improved compared with those before operation. The HMB group had no significant change, while the measures in the negative control group significantly decreased. Postoperative BI and HSS did not reach pre-injury levels in any of the four groups, but postoperative VAS score was significantly improved. However, there was no significant difference in BI, HSS, or VAS among the four groups. CONCLUSION: RT, with or without HMB supplementation, can effectively improve body composition and grip strength in elderly patients with sarcopenia after hip replacement at short-term follow-up. Simultaneously, use of exclusive HMB supplementation alone may also help to prevent decreases in muscle mass and grip strength in these patients.


Assuntos
Artroplastia de Quadril , Treinamento Resistido , Sarcopenia , Idoso , Suplementos Nutricionais , Feminino , Humanos , Hidroxiácidos/farmacologia , Masculino , Músculo Esquelético , Sarcopenia/patologia , Sarcopenia/prevenção & controle , Valeratos/farmacologia , Valeratos/uso terapêutico
6.
Poult Sci ; 101(3): 101661, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35042180

RESUMO

In addition to offering methionine, 2-hydroxy-4-methylthiobutyric acid (HMTBa) is also an organic acid and shows excellent bacteriostasis. Therefore, 3 experiments were conducted to determine the influence of drinking water supplemented HMTBa in combination with acidifier on performance, intestinal development, and microflora in broilers. The addition of different concentration (0.02-0.20%) of the blend of HMTBa and other acids significantly reduced the pH of water and exerted antimicrobial activity in dose-dependent manner in vitro. The outcomes from animal trial consisting of the drinking water with blended acidifier at 0.00, 0.05, 0.10, 0.15, and 0.20% indicated that the water with 0.15 or 0.20% acidifier resulted in linear and quadratic higher body weight at 42 d, gain and water consumption during 1 to 42 d (P < 0.05). In experiment 3, responding to graded blended acidifier in drinking water, birds receiving 0.10, 0.15, and 0.20% acidifier decreased the internal pH of gastrointestinal tract and muscle, and exhibited increased duodenal weight, length, villus high, and the ratio of villus high to crypt depth. Drinking water with 0.2% blended acidifier increased the abundance of probiotics (Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae) and decreased the account of pathogenic bacteria such as Desulfovibrionaceae. Alternations in gut microflora were closely related to the metabolism of carbohydrate, amino acid, and vitamins. These findings, therefore, suggest that drinking water with 0.10 to 0.13% the combination HMTBa with acidifier might benefit to intestinal development and gut microbiota, and the subsequent produce a positive effect on the performance of broilers.


Assuntos
Água Potável , Microbioma Gastrointestinal , Ração Animal/análise , Animais , Butiratos , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Hidroxiácidos/metabolismo
7.
Eur J Pharmacol ; 901: 174095, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862063

RESUMO

Previous clinical studies have shown that anisodamine could improve no-reflow phenomenon and prevent reperfusion arrhythmias, but whether this protective effect is related to the antagonism of the M-type cholinergic receptor or other potential mechanisms is uncertain. The aim of the present study was to investigate the role of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) in cardioprotective effect of anisodamine against ischemia/reperfusion injury. Anisodamine and 5- hydroxydecanoic acid were used to explore the relationship between anisodamine and mitoK ATP . Using a Langendorff isolated heart ischemia/reperfusion injury model, hemodynamic parameters and reperfusion ventricular arrhythmia were evaluated; in addition, changes in myocardial infarct size, cTnI from coronary effluent and myocardial ultrastructure, as well as ATP, MDA and SOD in myocardial tissues, were detected. In the hypoxia/reoxygenation injury model of neonatal rat cardiomyocyte, cTnI release in the culture medium and levels of ATP, MDA and SOD in cardiomyocytes and mitochondrial membrane potential, were analyzed. Overall, anisodamine could significantly improve the hemodynamic indexes of isolated rat heart injured by ischemia/reperfusion, reduce the occurrence of ventricular reperfusion arrhythmia and myocardial infarction area, and improve the ultrastructural damage of myocardium and mitochondria. The in vitro results demonstrated that anisodamine could improve mitochondrial energy metabolism, reduce oxidative stress and stabilize mitochondrial membrane potential. The cardioprotective effects were significantly inhibited by 5-hydroxydecanoic acid. In conclusion, this study suggests that the opening of mitoK ATP could play an important role in the protective effect of anisodamine against myocardial ischemia/reperfusion injury.


Assuntos
Cardiotônicos/uso terapêutico , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Canais de Potássio/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Alcaloides de Solanáceas/uso terapêutico , Trifosfato de Adenosina/metabolismo , Animais , Arritmias Cardíacas/prevenção & controle , Ácidos Decanoicos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hidroxiácidos/farmacologia , Técnicas In Vitro , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Alcaloides de Solanáceas/antagonistas & inibidores , Superóxido Dismutase/metabolismo
8.
Biomed Res Int ; 2020: 3039184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134375

RESUMO

Inflammatory response during myocardial ischemia reperfusion injury (MIRI) is essential for cardiac healing, while excessive inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanism of these uncontrolled inflammatory processes has a significant impact during the MIRI therapy. Here, we found a critical role of ATP-sensitive potassium channels (KATP) in the inflammatory response of MIRI and its potential mechanism and explored the effects of Panax Notoginseng Saponins (PNS) during this possess. Rats underwent 40 min ischemia by occlusion of the left anterior descending (LAD) coronary artery and 60 min of reperfusion. PNS was treated at the corresponding time point before operation; 5-hydroxydecanoate (5-HD) and glybenclamide (Gly) (or Nicorandil (Nic)) were used as pharmacological blocker (or nonselective opener) of KATP. Cardiac function and pathomorphology were evaluated and a set of molecular signaling experiments was tested. KATP current density was measured by patch-clamp. Results revealed that in MIRI, PNS pretreatment restored cardiac function, reduced infarct size, and ameliorated inflammation through KATP. However, inhibiting KATP by 5-HD and Gly significantly reversed the effects, including NLRP3 inflammasome and inflammatory mediators IL-6, MPO, TNF-α, and MCP-1. Moreover, PNS inhibited the phosphorylation and nuclear translocation of NF-κB in I/R myocardium when the KATP was activated. Importantly, PNS promoted the expression of subunits and activation of KATP. The study uncovered KATP served as a new potential mechanism during PNS modulating MIRI-induced inflammation and promoting injured heart recovery. The manipulation of KATP could be a potential therapeutic approach for MIRI and other inflammatory diseases.


Assuntos
Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/química , Canais KATP/genética , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Saponinas/farmacologia , Animais , Cardiotônicos/isolamento & purificação , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ácidos Decanoicos/farmacologia , Regulação da Expressão Gênica , Glibureto/farmacologia , Hidroxiácidos/farmacologia , Inflamação , Interleucina-6/genética , Interleucina-6/metabolismo , Canais KATP/agonistas , Canais KATP/antagonistas & inibidores , Canais KATP/metabolismo , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Nicorandil/farmacologia , Técnicas de Patch-Clamp , Peroxidase/genética , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
BMC Mol Cell Biol ; 21(1): 31, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306897

RESUMO

BACKGROUND: Cytoprotection afforded by mitochondrial ATP-sensitive K+-channel (mKATP-channel) opener diazoxide (DZ) largely depends on the activation of potassium cycle with eventual modulation of mitochondrial functions and ROS production. However, generally these effects were studied in the presence of Mg∙ATP known to block K+ transport. Thus, the purpose of our work was the estimation of DZ effects on K+ transport, K+ cycle and ROS production in rat liver mitochondria in the absence of Mg∙ATP. RESULTS: Without Mg·ATP, full activation of native mKATP-channel, accompanied by the increase in ATP-insensitive K+ uptake, activation of K+-cycle and respiratory uncoupling, was reached at ≤0.5 µM of DZ,. Higher diazoxide concentrations augmented ATP-insensitive K+ uptake, but not mKATP-channel activity. mKATP-channel was blocked by Mg·ATP, reactivated by DZ, and repeatedly blocked by mKATP-channel blockers glibenclamide and 5-hydroxydecanoate, whereas ATP-insensitive potassium transport was blocked by Mg2+ and was not restored by DZ. High sensitivity of potassium transport to DZ in native mitochondria resulted in suppression of mitochondrial ROS production caused by the activation of K+-cycle on sub-micromolar scale. Based on the oxygen consumption study, the share of mKATP-channel in respiratory uncoupling by DZ was found. CONCLUSIONS: The study of mKATP-channel activation by diazoxide in the absence of MgATP discloses novel, not described earlier, aspects of mKATP-channel interaction with this drug. High sensitivity of mKATP-channel to DZ results in the modulation of mitochondrial functions and ROS production by DZ on sub-micromolar concentration scale. Our experiments led us to the hypothesis that under the conditions marked by ATP deficiency affinity of mKATP-channel to DZ can increase, which might contribute to the high effectiveness of this drug in cardio- and neuroprotection.


Assuntos
Trifosfato de Adenosina/metabolismo , Diazóxido/farmacologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Canais de Potássio/metabolismo , Potássio/metabolismo , Animais , Ácidos Decanoicos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Glibureto/farmacologia , Hidroxiácidos/farmacologia , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/genética , Canais KATP/metabolismo , Magnésio/metabolismo , Mitocôndrias Hepáticas/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/genética , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
10.
Wei Sheng Yan Jiu ; 49(2): 285-319, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32290947

RESUMO

OBJECTIVE: To establish a method for determination of ten kinds of α-hydroxy acids in cosmetics with quantitative analysis of multi-components by single marker(QAMS). METHODS: The analytes were separated by high performance liquid chromatography on a Venusil XBP C_8 column(4. 6 mm×250 mm, 5 µm), with the mobile phases of ammonium dihydrogen phosphate buffer-methonal under a gradient elution. The components were detected at the wavelengths of 214 nm using a diode array detector. Citric acid was used as the internal standard to determine the relative correction factors(RCFs) of the nine other α-hydroxy acids, in order to calculate their contents in samples by their RCFs. RESULTS: Good linearity with correlation coefficients greater than 0. 9994 was obtained for all the analytes. Stabilities within 24 h and precision of ten α-hydroxy acids were all good. Recoveries of the method were from 89. 3% to 105. 0% at three concentration levels, with the relative standard deviation(RSD) from 1. 0% to 2. 9%. Nine batches of samples were determined by QAMS, as well as the standard curve method(SCM). The relative average deviations(RAD) were below 3. 2% between the result of the two method, which showed good feasibility and accuracy of QAMS. CONCLUSION: The method is simple, accurate and beneficial to the saving of reference substances, which is suitable for the determination of ten kinds of α-hydroxy acids in cosmetics.


Assuntos
Cosméticos/análise , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Hidroxiácidos
11.
Molecules ; 24(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717454

RESUMO

Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1-3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1-3) were established using modified Mosher's method together with analysis of NMR data for their acetonide derivatives. All the isolates (1-3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.


Assuntos
Ascomicetos/metabolismo , Ácidos Decanoicos/química , Ácidos Decanoicos/metabolismo , Hidroxiácidos/química , Hidroxiácidos/metabolismo , Aconitum/genética , Aconitum/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Ascomicetos/genética , Bactérias/efeitos dos fármacos , Ácidos Decanoicos/síntese química , Ácidos Decanoicos/farmacologia , Humanos , Hidroxiácidos/síntese química , Hidroxiácidos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular
12.
Eur J Pharmacol ; 862: 172636, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491405

RESUMO

Several studies have reported that CORM-3, a water-soluble carbon monoxide releasing molecule, elicits cardioprotection against myocardial infarction but the mechanism remains to be investigated. Numerous reports indicate that inhibition of pH regulators, the Na+/H+ exchanger (NHE) and Na+/HCO3- symporter (NBC), protect cardiomyocytes from hypoxia/reoxygenation injury by delaying the intracellular pH (pHi) recovery at reperfusion. Our goal was to explore whether CORM-3-mediated cytoprotection involves the modulation of pH regulation. When added at reoxygenation, CORM-3 (50 µM) reduced the mortality of cardiomyocytes exposed to 3 h of hypoxia and 2 h of reoxygenation in HCO3--buffered solution. This effect was lost when using inactive iCORM-3, which is depleted of CO and used as control, thus implicating CO as the mediator of this cardioprotection. Interestingly, the cardioprotective effect of CORM-3 was abolished by switching to a bicarbonate-free medium. This effect of CORM-3 was also inhibited by 5-hydroxydecanoate, a mitochondrial ATP-dependent K+ (mKATP) channel inhibitor (500 µM) or PD098059, a MEK1/2 inhibitor (10 µM). In additional experiments and in the absence of hypoxia-reoxygenation, intracellular pH was monitored in cardiomyocytes exposed to cariporide to block NHE activity. CORM-3 inhibited alkalinisation and this effect was blocked by PD098059 and 5-HD. In conclusion, CORM-3 protects the cardiomyocyte against hypoxia-reoxygenation injury by inhibiting a bicarbonate transporter at reoxygenation, probably the Na+/HCO3- symporter. This cardioprotective effect of CORM-3 requires the activation of mKATP channels and the activation of MEK1/2.


Assuntos
Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Monóxido de Carbono/metabolismo , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultura/química , Ácidos Decanoicos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Flavonoides/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Hidroxiácidos/farmacologia , Canais KATP/antagonistas & inibidores , Canais KATP/metabolismo , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 2/metabolismo , Masculino , Camundongos , Mitocôndrias/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/patologia , Compostos Organometálicos/uso terapêutico , Cultura Primária de Células , Substâncias Protetoras/uso terapêutico
13.
Anal Bioanal Chem ; 411(25): 6655-6665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31410535

RESUMO

For the analysis of pigment-rich red yeast rice products, a fast quantitative high-performance thin-layer chromatography (HPTLC) method was newly developed and validated. The active ingredient lovastatin, present in lactone (LL) and hydroxy acid forms (LH), as well as the mycotoxin citrinin were analyzed in 19 red yeast rice products, including powders, dietary supplements, and Chinese proprietary medicines (Xuezhikang and Zhibituo). The HPTLC method including sample preparation allows a high throughput of matrix-rich samples (10 min per analysis) and is highly cost-efficient (running costs of 0.5 Euro per analysis). For a fast protocol, application volumes up to 10 µL were selected although higher application volumes will lower still the LODs, which were 30 mg/kg for LL and LH as well as 4 mg/kg for citrinin. Thanks to the minimalistic sample preparation, the overall mean recovery rate was good (109.9% ± 5.9%; repeated measurements of the three analytes per fresh sample preparation at three spike levels). Repeated calibrations (five per analyte) in the red yeast rice matrix showed highly satisfying determination coefficients (≥ 0.9991; mean 0.9996). For three analytes at three concentration levels, the obtained mean intermediate precisions in red yeast rice matrix analyzed over the whole procedure including sample preparation were highly satisfying (≤ 2.6%). Citrinin was not detectable in the samples down to the given LOD of 4.0 mg/kg for the 10-µL sample volume applied. The mean content of lovastatin in 15 RYR powders was 8.7 g/kg, with a rang of 1.5-26.2 g/kg. The content of lovastatin in Zhibituo tablets and Xuezhikang capsules was determined to be 2.7 and 11.1 g/kg, respectively. The two commercially available RYR dietary supplement samples showed the highest lovastatin contents of 40.7 and 41.4 g/kg. By these figures of merit, the HPTLC method was proven to be suited for the control of such matrix-rich, fermented food. Graphical abstract.


Assuntos
Anticolesterolemiantes/análise , Produtos Biológicos/análise , Citrinina/análise , Medicamentos de Ervas Chinesas/análise , Lovastatina/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina/métodos , Hidroxiácidos/análise , Lactonas/análise , Limite de Detecção
14.
J Pharmacol Exp Ther ; 370(3): 736-741, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31092539

RESUMO

Pasty polymers offer a platform for injectable implants for drug delivery. A library of biodegradable pasty polymers was synthesized by bulk ring-opening polymerization of lactide, glycolide, trimethylene carbonate, or caprolactone using castor oil or 12-hydroxy stearic acid as hydroxyl initiators and stannous octoate as the catalyst. Some of the polymers behaved as Newtonian liquids. Pasty polymers of poly(caprolactone) and poly(trimethylene carbonate) were stable under physiologic conditions for over 1 month in vitro, whereas polymers of poly(lactic-co-glycolic acid) degraded within 10 days. These pasty polymers offer a platform for pasty injectable biodegradable carriers for drugs and fillers. SIGNIFICANCE STATEMENT: New injectable pasty, in situ forming drug delivery systems are described and are advantageous due to their ease of administration, tunable viscosity, and biodegradability. Polyesters based on lactide, glycolide, trimethylene carbonate, and caprolactone, which are commonly used as absorbable implants and drug carriers, were conjugated onto natural hydroxyl fatty acids. These polymers have potential use as wrinkle fillers and drug carriers.


Assuntos
Plásticos Biodegradáveis , Óleo de Rícino/química , Hidroxiácidos/química , Lactonas/química , Polímeros , Portadores de Fármacos , Stents Farmacológicos , Ácidos Graxos/química , Injeções , Viscosidade
15.
Poult Sci ; 98(9): 3818-3827, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30839093

RESUMO

This study evaluated reduced dietary CP and supplementing amino acid analogs to sustain growth and carcass weight in 0- to 21-day-old Cobb × Avian-48 male broiler chicks. A total of 6 diets with 3 levels of CP (22.5, 19.5, and 16.5%) and 2 sources of AA analogs, either synthetic amino acids (SA) or keto-/hydroxy-acids (KA), were assigned randomly to 36 cages (8 chicks/cage) in a 3 × 2 factorial design. For SA diets, DL-Met, DL-Met + L-Ile, and D-Met + L-Ile + L-Val were used to supplement 22.5, 19.5, and 16.5% CP diets, respectively, and for corresponding KA diets, DL-Met was replaced with methionine hydroxy analog (MHA), L-Ile was replaced with keto-Ile, and L-Val was replaced with keto-Val. Water and all isocaloric diets (3,050 kcal ME/kg) were given ad libitum. Lowering dietary CP to 16.5% reduced BW at 7, 14, and 21 D (P ≤ 0.0001) and feed intake at 8 to 14, 15 to 21, and 0 to 21 D (P ≤ 0.001). Body weight gain (BWG) was reduced and feed-to-gain ratio (FGR) was increased (P ≤ 0.003 to 0.0001) at all times for chicks fed 16.5% CP; however, chicks fed 22.5 and 19.5% CP had comparable performance. Differences in 0 to 7 D BWG (SA, 122.9 vs. KA, 113.9 g/bird; P ≤ 0.04), a 0 to 21 D FGR cumulative effect (1.45 vs. 1.51; P ≤ 0.02), and a 15 to 21 D (P ≤ 0.04) and 0 to 21 D (P ≤ 0.05) CP × AA interaction were also observed. Greater liver weight among 16.5 vs. 19.5 or 22.5% CP fed chicks was found at 14 and 21 D (P ≤ 0.0001 and P = 0.06, respectively). Lower dietary CP reduced spleen weight on day 21 birds (P ≤ 0.0005) with lighter spleens among 16.5 and 19.5% vs. the 22.5% CP fed group (0.090, 0.095, 0.119 g/100 g BW, respectively). Breast weight at 21 D was significantly less for 16.5 vs. 22.5% CP fed chicks. Fat pad weight on day 21 was heaviest among 16.5% chicks (P ≤ 0.0004). Overall, lowering dietary CP to 16.5% had a negative effect, but keto-acid supplementation supported 0 to 21 D broiler growth compared to SA; however, transamination efficiency of KA may be lower for 0 to 7D old chicks compared to older birds.


Assuntos
Galinhas/fisiologia , Dieta com Restrição de Proteínas/veterinária , Hidroxiácidos/metabolismo , Cetoácidos/metabolismo , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Proteínas Alimentares/análise , Suplementos Nutricionais/análise , Hidroxiácidos/administração & dosagem , Cetoácidos/administração & dosagem , Masculino , Distribuição Aleatória
16.
Mater Sci Eng C Mater Biol Appl ; 85: 79-87, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29407160

RESUMO

Scaffolds with extracellular matrix-like fibrous morphology, suitable mechanical properties, biomineralization capability, and excellent cytocompatibility are desired for bone regeneration. In this work, fibrous and degradable poly(ester urethane)urea (PEUU) scaffolds reinforced with titanium dioxide nanoparticles (nTiO2) were fabricated to possess these properties. To increase the interfacial interaction between PEUU and nTiO2, poly(ester urethane) (PEU) was grafted onto the nTiO2. The scaffolds were fabricated by electrospinning and exhibited fiber diameter of <1µm. SEM and EDX mapping results demonstrated that the PEU modified nTiO2 was homogeneously distributed in the fibers. In contrast, severe agglomeration was found in the scaffolds with unmodified nTiO2. PEU modified nTiO2 significantly increased Young's modulus and tensile stress of the PEUU scaffolds while unmodified nTiO2 significantly decreased Young's modulus and tensile stress. The greatest reinforcement effect was observed for the scaffold with 1:1 ratio of PEUU and PEU modified nTiO2. When incubating in the simulated body fluid over an 8-week period, biomineralization was occurred on the fibers. The scaffolds with PEU modified nTiO2 showed the highest Ca and P deposition than pure PEUU scaffold and PEUU scaffold with unmodified nTiO2. To examine scaffold cytocompatibility, bone marrow-derived mesenchymal stem cells were cultured on the scaffold. The PEUU scaffold with PEU modified nTiO2 demonstrated significantly higher cell proliferation compared to pure PEUU scaffold and PEUU scaffold with unmodified nTiO2. The above results demonstrate that the developed fibrous nanocomposite scaffolds have potential for bone tissue regeneration.


Assuntos
Materiais Biomiméticos/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Nanocompostos/química , Poliuretanos/farmacologia , Alicerces Teciduais/química , Titânio/farmacologia , Animais , Líquidos Corporais/química , Cálcio/análise , Proliferação de Células/efeitos dos fármacos , Hidroxiácidos/síntese química , Hidroxiácidos/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanocompostos/ultraestrutura , Fósforo/análise , Poliuretanos/síntese química , Poliuretanos/química , Propionatos/síntese química , Propionatos/química , Ratos , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
17.
J Asian Nat Prod Res ; 19(11): 1143-1147, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28347167

RESUMO

A new oligostilbene, caragasinin C (1), and seven known compounds, betulinic acid (2), 4-hydroxybenzaldehyde (3), (‒)-medicarpin (4), wistin (5), (2E,4S)-4-hydroxy-2-nonenoic acid (6), pallidol (7), and (+)-α-viniferin (8), were isolated from the roots of Caragana sinica. The structure of caragasinin C was established on the basis of spectroscopic techniques, including HRESIMS, 1D and 2D-NMR.


Assuntos
Caragana/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Raízes de Plantas/química , Estilbenos/isolamento & purificação , Benzaldeídos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Hidroxiácidos/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Compostos Policíclicos/isolamento & purificação , República da Coreia , Estilbenos/química
18.
J Exp Biol ; 219(Pt 17): 2743-51, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27358470

RESUMO

The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how the mitoKATP channel protects against hypoxia-reoxygenation (H-R)-induced mitochondrial dysfunction in fish, we first determined the mitochondrial bioenergetic effects of two key modulators of the channel, diazoxide and 5-hydroxydecanoate (5-HD), using a wide range of doses. Subsequently, the effects of low and high doses of the modulators on mitochondrial bioenergetics and volume under normoxia and after H-R using buffers with and without magnesium and ATP (Mg-ATP) were tested. In the absence of Mg-ATP (mitoKATP channel open), both low and high doses of diazoxide improved mitochondrial coupling, but only the high dose of 5-HD reversed the post-H-R coupling-enhancing effect of diazoxide. In the presence of Mg-ATP (mitoKATP channel closed), diazoxide at the low dose improved coupling post-H-R, and this effect was abolished by 5-HD at the low dose. Interestingly, both low and high doses of diazoxide reversed H-R-induced swelling under mitoKATP channel open conditions, but this effect was not sensitive to 5-HD. Under mitoKATP channel closed conditions, diazoxide at the low dose protected the mitochondria from H-R-induced swelling and 5-HD at the low dose reversed this effect. In contrast, diazoxide at the high dose failed to reduce the swelling caused by H-R, and the addition of the high dose of 5-HD enhanced mitochondrial swelling. Overall, our study showed that in the presence of Mg-ATP, both opening of mitoKATP channels and bioenergetic effects of diazoxide were protective against H-R in fish mitochondria, while in the absence of Mg-ATP only the bioenergetic effect of diazoxide was protective.


Assuntos
Metabolismo Energético , Hipóxia/metabolismo , Mitocôndrias/metabolismo , Oncorhynchus mykiss/metabolismo , Oxigênio/farmacologia , Canais de Potássio/metabolismo , Substâncias Protetoras/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Soluções Tampão , Respiração Celular/efeitos dos fármacos , Ácidos Decanoicos/farmacologia , Diazóxido/farmacologia , Metabolismo Energético/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Hidroxiácidos/farmacologia , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos
19.
Semin Cutan Med Surg ; 35(2): 87-95, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27416314

RESUMO

Acne and rosacea are common inflammatory processes historically classified in the same disease category, but evolving understanding of their disparate pathophysiology and exacerbating factors have generated an enormous armamentarium of therapeutic possibilities. Patients seek over-the-counter therapies first when managing cutaneous disease; therefore, this review defines ingredients considered to be effective over-the-counter acne and rosacea products, their mechanisms, and safe formulations, including botanical components, oral supplements, and other anecdotal options in this vast skin care domain.


Assuntos
Acne Vulgar/tratamento farmacológico , Peróxido de Benzoíla/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Medicamentos sem Prescrição/administração & dosagem , Rosácea/tratamento farmacológico , Acne Vulgar/epidemiologia , Administração Cutânea , Adstringentes/administração & dosagem , Detergentes/administração & dosagem , Medicina Baseada em Evidências , Saúde Global , Humanos , Hidroxiácidos/administração & dosagem , Cinetina/administração & dosagem , Niacinamida/administração & dosagem , Fototerapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resorcinóis/administração & dosagem , Rosácea/epidemiologia , Salicilatos/administração & dosagem , Enxofre/administração & dosagem , Protetores Solares/administração & dosagem , Óleo de Melaleuca/administração & dosagem , Resultado do Tratamento , Tretinoína/administração & dosagem , Zinco/administração & dosagem
20.
Food Chem ; 212: 585-9, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27374571

RESUMO

A new method for determining the acid values (AVs) of edible oils based on the OH stretching band was developed. The oil sample was diluted with carbon tetrachloride and was placed in a quartz cuvette with a thickness of 1cm to record the FTIR spectrum. The peak at 3535cm(-1), which corresponds to the OH stretch of the carboxyl group in free fatty acids, together with the peak valley at 3508cm(-1) and the spectral data in the range of 3340-3390cm(-1) were used to determine the AV of the edible oil. The excellent linear relationship between the AVs measured in this work and those measured using a titration method, with a correlation coefficient (R) of 0.9929, indicates that the present procedure can be applied as an alternative to the classic method for determining the AVs of edible oils.


Assuntos
Ácidos Graxos não Esterificados/análise , Óleos de Plantas/análise , Alimentos , Hidroxiácidos/análise , Óleos de Plantas/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
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