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1.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 24-29, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430045

RESUMO

The genetics of organisms play a vital role in the development of coronary artery disease (CAD), with its heritability estimated at approximately 50-60%. For this purpose, we examined the relationship between CAD risk and C12orf43/rs2258287 polymorphisms in the Pakistani population. In this study based on the genetic approach to dyslipidemia, a total of 200 subjects were included from the southern Punjab. The biochemical analysis of parameters (total cholesterol, triglycerides, blood glucose, high-density lipoprotein, and low-density lipoprotein) was carried out along with molecular analysis using an ARMS-PCR-based assay for single-nucleotide polymorphism (SNP) C12orf43/rs2258287 to identify the genotype. Genotypes showed a substantial correlation with both family history and metabolic markers. The cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides and blood glucose levels were higher while the high-density lipoprotein cholesterol (HDL-C) level was lower significantly (p<0.05) in cases than in controls. Age, pulse rate, diabetes, physical activity, smoking, family history, and dietary habits were also significantly associated (p<0.05) with CAD individuals. The SNP C12orf43/rs2258287 also showed an association with CAD in the population of southern Punjab. Based upon this study, it could be concluded that CAD is characterized by an unfavorable lipid profile in association with SNP C12orf43/rs2258287.


Assuntos
Doença da Artéria Coronariana , Proteínas , Humanos , Glicemia , Colesterol , LDL-Colesterol , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Lipoproteínas HDL , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos , Proteínas/genética
2.
Chem Biodivers ; 20(9): e202300881, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37531600

RESUMO

This study analysed some physicochemical and quality parameters of 176 royal jelly (RJ) samples from different regions of Türkiye, collected over different years and seasons. According to the obtained results, the moisture percentage varied between 47.36 % and 69.58 %, with no statistically significant differences seen across various seasons and areas (p>0.05). The average value of 10-hydroxy-2-decenoic acid (10-HDA), which varies according to factors such as season, region, and year, was determined to be 2.32 %. It was also seen that this value was close to the international standard. The values of total acidity ranged from 28-58 mL 1 N NaOH/100 g. Furthermore, statistical significance (p<0.001) was observed for the year-region interaction in relation to 10-HDA and total acidity. The pH measurement results for all samples confirmed the acidic nature of the samples and resulted in a range between 3.45 and 3.80. And the pH variability was also found to be statistically significant for years (p=0.002) and regions (p=0.011). Finally, the correlation analysis between moisture (%), 10-HDA (%), total acidity, and pH revealed no statistically significant or strong differences. This comprehensive study, supported by statistical analyses, is thought to be a useful reference for future research on RJ.


Assuntos
Ácidos Graxos Monoinsaturados , Ácidos Graxos , Ácidos Graxos/química , Ácidos Graxos Monoinsaturados/análise , Ácidos Graxos Monoinsaturados/química
3.
Chem Biodivers ; 20(5): e202300305, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37058679

RESUMO

This study focused on the protective effects of different types of propolis extracts on gastric mucosa in indomethacin-induced rats. The animals were divided into nine groups: control, negative control (ulcer), positive control (omeprazole), and experimental groups, which were summarized by 200, 400, and 600 mg/kg, bw for aqueous-based and ethanol, respectively. According to the histopathological evaluation, more than others, the doses of 200 and 400 mg/kg of aqueous-based propolis extracts had different degrees of positive effects on the gastric mucosa. Generally, the biochemical analyses of the gastric tissue showed a correlation with microscopic evaluations. According to the phenolic profile analysis, while pinocembrin (684.34±1.70 µg/ml) and chrysin (540.54±9.06 µg/ml) were the most abundant phenolics in the ethanolic extract, ferulic acid (53.77±0.07 µg/ml) and p-coumaric acid (52.61±0.42 µg/ml) dominated the aqueous-based extract. Also, the total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of the ethanolic extract showed almost nine-fold superiority compared to the aqueous-based extracts. Based on data from preclinical data, it was decided that the best doses for the main goal of the study were 200 mg and 400 mg/kg, bw for aqueous-based propolis extract.


Assuntos
Própole , Úlcera Gástrica , Ratos , Animais , Própole/farmacologia , Própole/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Etanol/química , Água , Mucosa Gástrica , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química
4.
Pharm Res ; 39(9): 2179-2190, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35915321

RESUMO

AIM: Widespread clinical application of vascularized composite allotransplantation (VCA) has been limited by the need for lifelong systemic immunosuppression to prevent rejection. Our goal was to develop a site-specific immunosuppressive strategy that promotes VCA allograft survival and minimizes the risk of systemic side effects. METHODS: Tacrolimus loaded polycaprolactone (TAC-PCL) disks were prepared and tested for their efficacy in sustaining VCA allograft survival via site-specific immunosuppression. Brown Norway-to-Lewis rat hind limb transplantations were performed; animals received one TAC disk either in the transplanted (DTx) or in the contralateral non-transplanted (DnonTx) limbs. In another group, animals received DTx and lymphadenectomy on Tx side. Blood and allograft levels of TAC were measured using LC-MS/MS. Systemic toxicity was evaluated. RESULTS: Animals that received DTx achieved long-term allograft survival (> 200 days) without signs of metabolic and infectious complications. In these animals, TAC blood levels were low but stable between 2 to 5 ng/mL for nearly 100 days. High concentrations of TAC were achieved in the allografts and the draining lymph nodes (DLN). Animals that underwent lymphadenectomy rejected their allograft by 175 days. Animals that received DnonTx rejected their allografts by day 70. CONCLUSION: Controlled delivery of TAC directly within the allograft (with a single TAC disk) effectively inhibits rejection and prolongs VCA allograft survival, while mitigating the complications of systemic immunosuppression. There was a survival benefit of delivering TAC within the allograft as compared to a remote site. We believe this approach of local drug delivery has significant implications for drug administration in transplantation.


Assuntos
Aloenxertos Compostos , Tacrolimo , Aloenxertos , Animais , Cromatografia Líquida , Sobrevivência de Enxerto , Terapia de Imunossupressão , Imunossupressores/farmacologia , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Tacrolimo/farmacologia , Espectrometria de Massas em Tandem
5.
Chem Biodivers ; 19(12): e202200835, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36282115

RESUMO

The purpose of this research was to identify the biological activity of Turkish pine honeys and the most abundant phenolic compound(s) to guide future studies to be done about this type of honey. Moreover, this will provide the chance to introduce Turkish pine honeys by elucidating a distinct parameter compared to other forms of honey reported in the literature. To this end, microscopic examination based on the number of honeydew elements (NHE) and the number of total pollen (NTP) grains was performed on 17 samples of pine honeys from the Aegean region of Turkey. Then 18 commonly-occurring phenolic standards were used in high-performance liquid chromatography (HPLC) to examine the samples. Each sample was tested for individual phenolic compounds, as well as total phenolic content (TPC), total flavonoid content (TFC), and ferric reducing antioxidant power (FRAP). As shown by the numerical data, the values for NHE and NTP were 6600-144000 and 3000-75000, respectively. In addition, the general means of TPC, TFC, and FRAP values for the samples were 53.000 mg GAE/100 g fresh sample, 1.944 mg QE/100 g fresh sample, and 3.455 µmol FeSO4 /g fresh sample, respectively. Protocatechuic acid predominated with a range of 197.841-780.227 µg phenolic /100 g sample in all samples. According to the general mean for values detected in the samples, p-hydroxybenzoic acid and benzoic acid were the second and third markers for Turkish pine honey samples. It is believed that these results will help efforts to set standards for pine honey on a national and global scale.


Assuntos
Mel , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Mel/análise , Fenóis/química
6.
Pharm Res ; 37(11): 222, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067715

RESUMO

AIM: The high doses of oral tacrolimus (TAC) (1,2) necessary to prevent acute rejection (AR) after vascularized composite allotransplantation (VCA) are associated with systemic adverse effects. The skin is the most antigenic tissue in VCA and the primary target of AR. However, the short-term use of topical TAC (Protopic®), as an off-label adjunct to oral TAC, to treat AR episodes pro re nata (PRN), has yielded inconsistent results. There is lack of data on the pharmacokinetics and tissue distribution of topical TAC in VCA, that hampers our understanding of the reasons for unreliable efficacy. Toward this goal, we evaluated the ability of topical TAC to achieve high local tissue concentrations at the site of application with low systemic concentrations. MATERIALS AND METHODS: We assessed the pharmacokinetics and tissue distribution of topical TAC (Protopic®, 0.03%) after single or repeated topical application in comparison to those after systemic delivery in rats. Animals received a single topical application of TAC ointment (Group 1) or an intravenous (IV) injection of TAC (Group 2) at a dose of 0.5 mg/kg. In another experiment, animals received daily topical application of TAC ointment (Group 3), or daily intraperitoneal (IP) injection of TAC (Group 4) at a dose of 0.5 mg/kg for 7 days. TAC concentrations in blood and tissues were analyzed by Liquid Chromatography-Mass Spectrometry (LC/MS-MS). RESULTS: Following single topical administration, TAC was absorbed slowly with a Tmax of 4 h and an absolute bioavailability of 11%. The concentrations of TAC in skin and muscle were several folds higher than whole blood concentrations. Systemic levels remained subtherapeutic (< 3 ng/ml) with repeated once daily applications. CONCLUSION: Topical application of TAC ointment (Protopic®, 0.03%) at a dose of 0.5 mg/kg/day provided high concentrations in the local tissues with low systemic exposure. Repeated topical administration of TAC is well tolerated with no local or systemic adverse effects. This study confirms the feasibility of topical application of TAC for site specific graft immunosuppression and enables future applications in VCA.


Assuntos
Inibidores de Calcineurina/farmacocinética , Aloenxertos Compostos/transplante , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Alotransplante de Tecidos Compostos Vascularizados , Administração Tópica , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/sangue , Aloenxertos Compostos/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Injeções Intravenosas , Masculino , Músculo Esquelético/metabolismo , Estudo de Prova de Conceito , Ratos Endogâmicos Lew , Pele/metabolismo , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Distribuição Tecidual , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos
7.
J Enzyme Inhib Med Chem ; 31(3): 490-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25942364

RESUMO

The aim of this study was to evaluate new natural inhibitor sources for the enzymes urease and xanthine oxidase (XO). Chestnut, oak and polyfloral honey extracts were used to determine inhibition effects of both enzymes. In addition to investigate inhibition, the antioxidant capacities of these honeys were determined using total phenolic content (TPC), ferric reducing antioxidant power (FRAP), and DPPH radical scavenging activity assays. Due to their high phenolic content, chestnut and oak honeys are found to be a powerful source for inhibition of both enzymes. Especially, oak honeys were efficient for urease inhibition with 0.012-0.021 g/mL IC50 values, and also chestnut honeys were powerful for XO inhibition with 0.028-0.039 g/mL IC50 values. Regular daily consumption of these honeys can prevent gastric ulcers deriving from Helicobacter pylori and pathological disorders mediated by reactive oxygen species.


Assuntos
Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/farmacologia , Mel , Urease/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Canavalia/enzimologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Leite/enzimologia , Relação Estrutura-Atividade , Urease/metabolismo , Xantina Oxidase/metabolismo
8.
J Enzyme Inhib Med Chem ; 31(4): 599-602, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26076195

RESUMO

The purpose of this study was to investigate the anti-hyaluronidase activities of honeys from different botanical origins honeys in order to determine their anti-inflammatory properties. The total phenolic contents, total flavonoids and total tannin levels of six types of honey, chestnut, oak, heather, pine, buckwheat and mixed blossom, were determined. Concentration-related inhibition values were tested turbidimetrically on bovine testis hyaluronidase (BTHase) as IC50 (mg/mL). All honeys exhibited various concentration-dependent degrees of inhibition against BTHase. Inhibition values varied significantly depending on honeys' levels of phenolic contents, flavonoid and tannin. The honeys with the highest anti-hyaluronidase activity were oak, chestnut and heather. In conclusion, polyphenol-rich honeys have high anti-hyaluronidase activity, and these honeys have high protective and complementary potential against hyaluronidase-induced anti-inflammatory failures.


Assuntos
Inibidores Enzimáticos/farmacologia , Mel , Hialuronoglucosaminidase/antagonistas & inibidores , Polifenóis/farmacologia , Testículo/enzimologia , Animais , Bovinos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Hialuronoglucosaminidase/metabolismo , Masculino , Polifenóis/química , Relação Estrutura-Atividade
9.
J Enzyme Inhib Med Chem ; 31(sup3): 96-104, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27440492

RESUMO

This study was planned to investigate some physicochemical and anti-inflammatory, antioxidant, antimicrobial properties of three different degrees of unifloral characters of chestnut honeys. Antihyaluronidase, antiurease and antimicrobial activities were evaluated as anti-inflammatory characteristics. Total phenolic contents, flavonoids, tannins, phenolic profiles, ferric-reducing antioxidant power (FRAP), scavenging activities of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were evaluated as antioxidant properties. Color, optical rotation, conductivity, moisture, pH and ash content were evaluated as physicochemical parameters, and some sugars content, prolin, diastase, HMF and minerals (Na, K, Ca, P, Fe, Cu and Zn) were evaluated as chemical and biochemical parameters. All studied physicochemical and biological active properties were changed in line with the unifloral character of the chestnut honeys. A higher unifloral character was found associated with greater apitherapeutic capacity of the honey, as well as biological active compounds.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Fagaceae/química , Mel , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bactérias/efeitos dos fármacos , Bovinos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Fungos/efeitos dos fármacos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Urease/antagonistas & inibidores , Urease/metabolismo
10.
J Sep Sci ; 37(8): 997-1003, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24478225

RESUMO

This paper describes a GC-MS method for the determination of naproxen in human plasma. Naproxen and internal standard ibuprofen were extracted from plasma using a liquid-liquid extraction method. Derivatization was carried out using N-methyl-N-(trimethylsilyl)trifluoroacetamide. The calibration curve was linear between the concentration range of 0.10-5.0 µg/mL. Intra- and interday precision values for naproxen in plasma were <5.14, and accuracy (relative error) was better than 4.67%. The extraction recoveries of naproxen from human plasma were between 93.0 and 98.9%. The LOD and LOQ of naproxen were 0.03 and 0.10 µg/mL, respectively. Also, this assay was applied to determine the pharmacokinetic parameters of naproxen in six healthy Turkish volunteers who had been given 220 mg naproxen.


Assuntos
Naproxeno/sangue , Adulto , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Humanos , Ibuprofeno/sangue , Extração Líquido-Líquido , Naproxeno/administração & dosagem , Naproxeno/farmacocinética , Sensibilidade e Especificidade
11.
J Enzyme Inhib Med Chem ; 29(6): 829-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24246090

RESUMO

In this study, firstly, antioxidant and polyphenol oxidase (PPO) properties of Yomra apple were investigated. Seventeen phenolic constituents were measured by reverse phase-high-performance liquid chromatography (RP-HPLC). Total phenolic compounds (TPCs), ferric reducing antioxidant power (FRAP) and 2, 2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activities were performed to measure antioxidant capacity. Some kinetic parameters (Km, Vmax), and inhibition behaviors against five different substrates were measured in the crude extract. Catechin and chlorogenic acid were found as the major components in the methanolic extract, while ferulic acid, caffeic acid, p-hydroxybenzoic acid, quercetin and p-coumaric acid were small quantities. Km values ranged from 0.70 to 10.10 mM in the substrates, and also 3-(4-hydroxyphenyl) propanoic acid (HPPA) and L-DOPA showed the highest affinity. The inhibition constant of Ki were ranged from 0.05 to 14.90 mM against sodium metabisulphite, ascorbic acid, sodium azide and benzoic acid, while ascorbic acid and sodium metabisulphite were the best inhibitors.


Assuntos
Antioxidantes/química , Catequina/química , Catecol Oxidase/química , Ácido Clorogênico/química , Malus/química , Proteínas de Plantas/química , Polifenóis/química , Antioxidantes/isolamento & purificação , Ácido Ascórbico/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Ácidos Cafeicos/química , Ácidos Cafeicos/isolamento & purificação , Catequina/isolamento & purificação , Catecol Oxidase/isolamento & purificação , Ácido Clorogênico/isolamento & purificação , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Inibidores Enzimáticos/química , Frutas/química , Cinética , Levodopa/química , Levodopa/isolamento & purificação , Oxirredução , Parabenos/química , Parabenos/isolamento & purificação , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Proteínas de Plantas/isolamento & purificação , Polifenóis/isolamento & purificação , Propionatos , Quercetina/química , Quercetina/isolamento & purificação , Sulfitos/química
12.
J Enzyme Inhib Med Chem ; 29(4): 469-75, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23914927

RESUMO

Grayanotoxin III (GTX3) was investigated for inhibition of all catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, i.e. CA I to CA XIV. It showed micromolar inhibition (KIs of 8.01 and 6.13 µM) for cytosolic isoforms CA I and II, respectively. GTX3 showed a submicromolar inhibition (KIs in the range of 0.51-2.15 µM) for the remaining cytosolic (CA III, VII and XIII), membrane-associated/transmembrane (CA IV, IX, XII and XIV), mitochondrial (CA VA and CA VB) and secreted (CA VI) isoforms. This inhibition profile is very different from that of the sulfonamide CA inhibitors (CAIs), which possess different clinical applications. A molecular docking study for GTX3 within the active sites of CA I and II assisted to the understanding of molecular mechanism of the ligand. The interesting inhibition profile, coupled with various possibilities of interacting with the enzyme active site make this family of natural compounds attractive leads for designing novel chemotypes acting as CAIs.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Diterpenos/farmacologia , Inibidores da Anidrase Carbônica/química , Simulação por Computador , Diterpenos/química , Relação Dose-Resposta a Droga , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Modelos Moleculares , Conformação Molecular , Soluções , Relação Estrutura-Atividade
13.
J AOAC Int ; 97(4): 1061-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25145138

RESUMO

This paper describes a GCIMS method for the determination of flurbiprofen in human plasma. Flurbiprofen and internal standard ibuprofen were extracted from plasma by using a liquid-liquid extraction method. Derivatization was carried out using N-Methyl-N-(trimethylsilyl)trifluoroacetamide. The calibration curve was linear between the concentration range of 0.10 and 5.0 microg/mL. Intraday and interday precision values for flurbiprofen in plasma were less than 5.49%, and accuracy (relative error) was better than 5.33%. The extraction recoveries of flurbiprofen from human plasma were between 93.6 and 98.6%. The LOD and LOQ of flurbiprofen were 0.03 and 0.10 microg/mL, respectively. This assay was applied to determine the pharmacokinetic parameters of flurbiprofen in healthy Turkish volunteers who had been given 100 mg of flurbiprofen.


Assuntos
Flurbiprofeno/sangue , Flurbiprofeno/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas , Humanos
14.
J Pharm Sci ; 113(6): 1607-1615, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38309457

RESUMO

AIM: The goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression. MATERIALS AND METHODS: Lewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment. Other groups were treated with STAC at a dose of 1 mg/kg/day for 7 days. On post-operative day (POD) 8, the STAC dose was dropped to 0.1 mg/kg/day for Group 2 and maintained at 1 mg/kg for Group 3. Group 4 received topical application of TAC and MPA on the transplanted (Tx) limb starting POD 8 without STAC. Group 5 received topical TAC and MPA on the contralateral non-Tx limb and Group 6 received topical TAC and MPA on the Tx limb starting POD 8 along with low dose STAC (0.1 mg/kg/day). Treatment was continued until the study end point was reached, defined as either grade 3 rejection or allograft survival exceeding 100 days. .We conducted sequential LC-MS/MS measurements to assess TAC and MPA concentrations in both blood/plasma and allograft tissues. Additionally, we evaluated markers indicative of organ toxicity associated with STAC immunosuppression. RESULTS: Compared to controls, topical therapy with TAC+MPA significantly prolonged allograft survival beyond 100 daysat very low dose STAC (0.1 mg/kg/day) (Group 6). The histopathological assessment of the grafts was consistent with the clinical outcomes. .Drug levels in blood/plasma remained low or undetectable, while allograft tissues showed higher drug concentrations compared to contralateral limb tissues (P<0.05). . Urinary creatinine clearance remained within the normal range at 2.5 mL/min. CONCLUSION: Combination therapy with topical TAC and MPA synergizes with a very low dose, corticosteroid- free-STAC regimen and facilitates rejection-free, prolonged VCA survival without morbidity.


Assuntos
Administração Tópica , Sobrevivência de Enxerto , Imunossupressores , Ácido Micofenólico , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Tacrolimo , Animais , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Sobrevivência de Enxerto/efeitos dos fármacos , Ratos , Masculino , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Terapia de Imunossupressão/métodos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Sinergismo Farmacológico , Aloenxertos Compostos/efeitos dos fármacos , Aloenxertos
15.
Hum Exp Toxicol ; 42: 9603271231168764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37021362

RESUMO

BACKGROUND: Epilepsy is a common disorder affecting approximately 50 million people worldwide. Oxidative stress is known to play an important role in the pathophysiology of diseases, including epilepsy. In this study, we investigated the effects of sennoside B on PTZ-induced seizures in rats. METHOD: The rats were grouped into Group Electroencephalography and Group Behavioral. Both Groups were divided into eight subgroups, and these subgroups were compared in terms of the time of first myoclonic jerk, Racine's Convulsion Scale, malondialdehyde levels, and brain superoxide dismutase activity. The experimental seizure model was performed with pentylenetetrazol. RESULTS: The spike percentage was significantly lower in groups that received sennoside B, and this beneficial effect was shown to be associated with the dose of sennoside B received. The RCS score was lower and the FJM onset time was higher in the sennoside B-administered groups. Additionally, brain MDA and brain aquaporin-3 levels were lower and brain SOD activity was higher in the sennoside-administered groups. CONCLUSIONS: The present study shows the beneficial effects of sennoside B on PTZ-induced convulsion in rats. It is considered that sennoside B which is a natural and safe product would be a good candidate for strengthening the management of epilepsy without serious side effects.


Assuntos
Epilepsia , Pentilenotetrazol , Convulsões , Animais , Ratos , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
16.
Turk J Chem ; 47(1): 171-184, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720866

RESUMO

In this study, some novel mono- and di-O-ß-D-glycopyranosyl chalcone analogs were designed, synthesized, and characterized. The chalcone derivatives were synthesized with good yields by base-catalyzed Claisen-Schmidt condensation in EtOH solution. Then these chalcones were reacted with TAGBr (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0-5 °C. Deacylated was carried out by the Zemplen's method with NaOCH3 in dry methanol results in substituted chalcone-O-glycosides (mono- and di-O-ß-D-glycopyranosyl chalcone analogs). The chemical structures of all synthesized compounds were elucidated based on IR, NMR spectral data, and mass spectrometry. Further, the compounds (7a-c, 8a-c, 12a-c, 16a-c, and 17a-c) were tested for their enzyme inhibition activity against α-glycosidase, tyrosinase, and AChE with in vitro and in silico analysis. Amongst them, compounds 12a-c, 16a-c, and 17a-c displayed moderate or less enzyme inhibition activity against α-glycosidase while other compounds 7a-c and 8a-c) were not active. Remarkably interesting enzyme inhibition effects, with IC50 values below 30.59 ± 0.30 µM were recorded with 7c (IC50=11.07 ± 0.55 µM) against tyrosinase.

17.
Braz J Microbiol ; 54(3): 2307-2317, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37171533

RESUMO

Bee bread (BB) and bee pollen (BP) are accepted as functional food and considered in medical properties due to its important bioactive components. These bee products show different biological properties, but researches on these aspects have not been clear yet. In present study, Anatolian BB and BP extracts were analyzed for the first time for their pollen type, total phenolic (TPC) and flavonoid content (TFC), and antimicrobial and antioxidant properties. Samples were analyzed for their antimicrobial efficacy by the agar well diffusion and MIC methods. HPLC analysis was used to identify the compounds in the BB and BP samples. Antioxidant activity was measured by the FRAP and DPPH methods. As a result of microscopy for pollen identification, Fagaceae family was dominant. Phenolic compound analysis showed that the amounts of p-coumaric acid and rutin were found to be the highest in BB and BP, respectively. Stronger antioxidant activity was obtained from BP. MIC values of BB were range from 250 to 12.5 µg/mL. The most susceptible bacterium was Mycobacterium smegmatis. The extract of BP was effective on all gram-negative bacteria with doses range from 250 µg/mL to 500 µg/mL. The lowest MIC value was detected with the concentration of 12.5 µg/mL against M. smegmatis. Anatolian BB and BP could be considered as a functional foods due to antioxidant activity and may be beneficial in the management and treatment of pathogenic bacteria because of high antimicrobial activity.


Assuntos
Anti-Infecciosos , Própole , Abelhas , Animais , Própole/farmacologia , Própole/química , Antioxidantes/farmacologia , Antioxidantes/análise , Turquia , Anti-Infecciosos/química , Fenóis/química , Bactérias , Pólen
18.
J Plast Reconstr Aesthet Surg ; 82: 284-290, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37279613

RESUMO

BACKGROUND: Migraine headache surgery has been recently reported and supported by studies as management to provide long-term relief in migraine sufferers. This study aimed to monitor the long-term results of patients who underwent migraine surgery in our clinic and determine the relationship between pain and anatomical anomalies. METHODS: A prospective review was conducted of 93 patients who underwent surgery for migraine headaches performed between 2017 and 2021 by the senior author (M.U.) and had at least 12 months of follow-up. Anatomical data were obtained by recording the findings during surgery. Migraine surgery was performed bilaterally in all patients. Anatomical symmetry differences between the right and left sides were recorded. RESULTS: A total of 79 (84.9%) patients experienced at least 50% reduction in migraine headache. Furthermore, 13 (14%) patients reported complete elimination of migraine headache. A significant difference was found before and after surgery in Migraine Disability Assessment score, migraine headache index, frequency, duration, and pain (p < 0.001). Also, 30 (32.3%) of the patients had bilateral headaches and 63 (67.7%) had primarily unilateral headaches. Then, 51 (81%) patients with mostly unilateral headache were anatomically asymmetrical and 12 (12%) were anatomically symmetrical. Patients with mostly unilateral headache were found to be anatomically highly asymmetrical (p < 0.005). CONCLUSIONS: This study shows that surgical treatment is effective and long-term protection and has mild complications that are easily tolerated by the patient. The fact that headache side and anatomical asymmetry were significant in this study supports the peripheral mechanism.


Assuntos
Transtornos de Enxaqueca , Humanos , Estudos Prospectivos , Transtornos de Enxaqueca/cirurgia , Cefaleia
19.
J Enzyme Inhib Med Chem ; 27(3): 395-402, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21740099

RESUMO

Different natural products and secondary metabolites from mushrooms, teas, honeys, mosses, plants and seaweeds were investigated for their in vitro inhibitory effects on human carbonic anhydrase (hCA, E.C.4.2.1.1) isoforms I and II. Inhibition data were correlated with the total phenol content in the extract and investigated with the pure compounds believed to be responsible for this activity. Methanolic extracts were prepared for 17 such pure chemicals present in the natural products and for 41 diverse natural products. The IC(50) values were in the range of 0.11-66.50 µg/mL against hCA I and of 0.09-54.54 µg/mL against hCA II, respectively. The total phenol content was in the range of 0.02-1318.96 (as milligrams of gallic acid equivalents) per gram of sample. These data offer new insights on possible novel classes of CA inhibitors based on natural products, possessing a range of chemical structures not present in the classical inhibitors with pharmacological applications, such as the sulfonamides and sulfamates.


Assuntos
Agaricales/química , Produtos Biológicos/farmacologia , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Mel , Plantas/química , Biocatálise , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/isolamento & purificação , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade
20.
BMC Complement Altern Med ; 12: 115, 2012 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-22862993

RESUMO

OBJECTIVE: This study aims to examine knowledge and attitudes towards Complementary and Alternative Medicine among medical students in Turkey, and find out whether they want to be trained in Complementary and Alternative Medicine (CAM). METHODS: A cross-sectional study was carried out between October and December 2010 among medical students. Data were collected from a total of seven medical schools. FINDINGS: The study included 943 medical students. The most well known methods among the students were herbal treatment (81.2 %), acupuncture (80.8 %), hypnosis (78.8 %), body-based practices including massage (77 %) and meditation (65.2 %), respectively. Acupuncture, aromatherapy, herbal treatment and meditation were better known among female participants compared to males (p < 0.05). Females and first year students, generally had more positive attitudes. A larger proportion of female students compared to male students reported that a doctor should be knowledgeable about CAM (p = 0.001), and this knowledge would be helpful in their future professional lives (p = 0.015). Positive attitudes towards and willingness to receive training declined as the number of years spent in the faculty of medicine increased. CONCLUSIONS: Majority of the medical students were familiar with the CAM methods widely used in Turkey, while most of them had positive attitudes towards CAM as well as willingness to receive training on the subject, and they were likely to recommend CAM methods to their patients in their future professional lives. With its gradual scientific development and increasing popularity, there appears a need for a coordinated policy in integrating CAM into the medical curriculum, by taking expectations of and feedback from medical students into consideration in setting educational standards.


Assuntos
Atitude , Terapias Complementares/psicologia , Conhecimento , Estudantes de Medicina/psicologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários , Turquia , Adulto Jovem
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