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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.
J Pharm Sci ; 2024 Feb 02.
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.

3.
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.

4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
Neurosci Lett ; 766: 136342, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34774703

RESUMO

Chronic stress is a potential problem associated with anxiety, depression, and cognitive dysfunction. Bee pollen, a powerful antioxidant, has many therapeutic effects. In this study, we aimed to examine the effects of one of the Anatolian bee pollens on depression/anxiety. 24 male Sprague Dawley rats were divided into 3 groups as control, stress, and bee pollen + stress. Bee pollen (200 mg/kg/day) was given to rats exposed to physical stress for 10 days. Open field test (OFT) and forced swimming test (FST) were applied to monitor the behavioral changes of the rats. After behavioral tests, the rats were euthanized. Brain-derived neurotrophic factor (BDNF), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) levels were measured by ELISA to evaluate neurological and biochemical changes in rat hippocampal tissue. In addition, malondialdehyde (MDA) and glutathione (GSH) levels in the brain were evaluated. According to the behavioral test results, bee pollen reduced anxiety-like behavior but did not affect depression-like behavior. We also found that bee pollen suppressed neuroinflammation while reducing oxidative stress and lipid peroxidation in hippocampal tissues. Moreover, bee pollen significantly increased the level of BDNF in the hippocampus. In conclusion, bee pollen reduced oxidative damage and neuroinflammation caused by immobilization stress in rat brain tissue. Therefore, we suggest that bee pollen may be an effective natural compound in alleviating the negative effects caused by immobilization stress.


Assuntos
Abelhas , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Doenças Neuroinflamatórias/etiologia , Pólen , Animais , Antioxidantes/farmacologia , Hipocampo/metabolismo , Masculino , Doenças Neuroinflamatórias/metabolismo , Ratos , Ratos Sprague-Dawley , Restrição Física/psicologia , Estresse Psicológico/psicologia
12.
J Food Biochem ; 46(4): e13921, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34477237

RESUMO

AIDS is a global disease caused by HIV, affecting millions of people and causing death. The current limitations of antiretroviral therapy used in the therapy of HIV/AIDS have led to the need to search for new and effective drugs from natural products, especially plants. Herewith, using the present study, the detection of HIV-1-RT inhibition of aqueous extract of Satureja spicigera (C.KOCH) BOISS. was performed for the first time. Besides, total phenolic content (TPC), analysis of phenolic constituents by RP-HPLC-DAD and antioxidant capacity by DPPH and Ferric reducing antioxidant power (FRAP) methods were determined for the first time. In addition, molecular docking studies were carried out between HIV-1-RT and phenolic substances, the presence of which was determined in the aqueous extract, for the determination of the phenolics that may be responsible for HIV-1-RT activity. HIV-1-RT inhibition was defined as IC50 : 22.83 µg/ml. Benzoic acid, vanillin, rutin, and chlorogenic acid were present as main phenolics in quantities of 621.96, 505.87, 349.33, and 323.23 µg phenolic/g extract, respectively. Further, TPC, DPPH, and FRAP were calculated as in the order of 151.69 mg GAE/g extract, 23.77 µg/ml, and 445.7 µmol TE/g extract. Chlorogenic acid (-8.48 kcal/mol) was found to be the most effective ligand in docking studies, with a value close to positive standard nevirapine (-9.35 kcal/mol). Hereby, although the aqueous extract of S. spicigera can be used as a natural antioxidant, the crude extract or its phenolics have the potential to be used in the treatment of AIDS due to its high HIV-1-RT activity. PRACTICAL APPLICATIONS: In this study, anti-HIV-1-RT and antioxidant activity and total phenolic content of Satureja spicigera aqueous extract were determined. In addition, HPLC analysis of some phytochemicals and the activities of these phytochemicals against HIV-1-RT enzyme was determined by molecular docking studies. The results showed that the aqueous extract of S. spicigera and some of the phytochemicals it contains have the potential to be used as a natural product against HIV infection or in the treatment of AIDS.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Satureja , Antioxidantes/química , Ácido Clorogênico , Cromatografia Líquida de Alta Pressão , Humanos , Simulação de Acoplamento Molecular , Fenóis/análise , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia
13.
Front Immunol ; 12: 591154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017323

RESUMO

Systems-level insights into inflammatory events after vascularized composite allotransplantation (VCA) are critical to the success of immunomodulatory strategies of these complex procedures. To date, the effects of tacrolimus (TAC) immunosuppression on inflammatory networks in VCA, such as in acute rejection (AR), have not been investigated. We used a systems biology approach to elucidate the effects of tacrolimus on dynamic networks and principal drivers of systemic inflammation in the context of dynamic tissue-specific immune responses following VCA. Lewis (LEW) rat recipients received orthotopic hind limb VCA from fully major histocompatibility complex-mismatched Brown Norway (BN) donors or matched LEW donors. Group 1 (syngeneic controls) received LEW limbs without TAC, and Group 2 (treatment group) received BN limbs with TAC. Time-dependent changes in 27 inflammatory mediators were analyzed in skin, muscle, and peripheral blood using Principal Component Analysis (PCA), Dynamic Bayesian Network (DyBN) inference, and Dynamic Network Analysis (DyNA) to define principal characteristics, central nodes, and putative feedback structures of systemic inflammation. Analyses were repeated on skin + muscle data to construct a "Virtual VCA", and in skin + muscle + peripheral blood data to construct a "Virtual Animal." PCA, DyBN, and DyNA results from individual tissues suggested important roles for leptin, VEGF, various chemokines, the NLRP3 inflammasome (IL-1ß, IL-18), and IL-6 after TAC treatment. The chemokines MCP-1, MIP-1α; and IP-10 were associated with AR in controls. Statistical analysis suggested that 24/27 inflammatory mediators were altered significantly between control and TAC-treated rats in peripheral blood, skin, and/or muscle over time. "Virtual VCA" and "Virtual Animal" analyses implicated the skin as a key control point of dynamic inflammatory networks, whose connectivity/complexity over time exhibited a U-shaped trajectory and was mirrored in the systemic circulation. Our study defines the effects of TAC on complex spatiotemporal evolution of dynamic inflammation networks in VCA. We also demonstrate the potential utility of computational analyses to elucidate nonlinear, cross-tissue interactions. These approaches may help define precision medicine approaches to better personalize TAC immunosuppression in VCA recipients.


Assuntos
Biomarcadores , Imunossupressores/farmacologia , Mediadores da Inflamação , Tacrolimo/farmacologia , Alotransplante de Tecidos Compostos Vascularizados , Animais , Modelos Animais de Doenças , Membro Posterior/transplante , Inflamassomos/metabolismo , Modelos Biológicos , Especificidade de Órgãos , Transplante de Órgãos , Ratos , Tacrolimo/administração & dosagem , Alotransplante de Tecidos Compostos Vascularizados/métodos
14.
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
15.
J Food Biochem ; 44(7): e13267, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32378224

RESUMO

The study investigated whether ethanolic propolis extract would exhibit an anti-diabetic effect in rats. The animals were divided into four groups of five rats each. Diabetic rats received 30% or 15% propolis extract at a dosage of 0.5 ml/100 g for 4 weeks. Data for the diabetic groups treated with 30% and 15% propolis showed a decrease in blood sugar levels from 393 ± 192.7 to 154 ± 28.0 mg/dl and from 386 ± 141.1 to 331.5 ± 123.74 mg/dl, respectively. Compared with the diabetic control group, an improvement was observed in both groups treated with propolis at the pancreatic, hepatic, and renal tissue levels. Antioxidant capacity, phenolic analysis, and the inhibition of α-amylase and α-glucosidase were also tested using the propolis samples to support in vivo data. Chrysin and caffeic acid phenyl ester were the dominant phenolics. The IC50 results for α-amylase (0.62 ± 0.00 µg/ml) and α-glucosidase (40.40 ± 0.09 µg/ml) were also encouraging. PRACTICAL APPLICATIONS: Bee products, non-synthetic compounds including propolis, are of great interest due to their potential therapeutic effects in metabolic disorders. The current study was designed and is now reported in order to confirm this potential benefit. The results obtained indicate that the higher concentration (30%) of ethanolic propolis extract exhibited excellent potential anti-diabetic activity by reducing blood sugar levels in diabetic rats. In addition, compared to the diabetic rat group, this extract exhibited a promising effect on the pancreatic, hepatic, and renal tissues of the propolis-treated groups. The current results indicate that propolis is a remarkable natural product with clinical potential in the treatment of diabetic disease.


Assuntos
Diabetes Mellitus Experimental , Própole , Animais , Antioxidantes/farmacologia , Abelhas , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , alfa-Glucosidases
16.
J Food Biochem ; 43(12): e13054, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31576596

RESUMO

This study focused on the concept of the possible protective effect of some honey types against HCl/ethanol-induced gastric ulcers in male Wistar albino rats. Rats were pretreated with rhododendron, chestnut, and oak honey orally with doses of 1.25 and 2.5 g/kg, bw (body weight) for three consecutive days. On fourth day, nothing was applied, and after the administration of anesthesia on the fifth day, their stomachs were surgically removed to investigate the histopathological examinations. Besides analyses of some blood serum profiles and antioxidant parameters of gastric tissue, some biochemical properties of honeys were investigated to support the histopathological results. The degrees of ulcer lesions in all groups revealed a statistically significant difference (p = .011). Although this difference originated from the additional ulcerative inducing effect of some honeys, the lower concentration rhododendron honey indicated more promising data than the positive control group (pantoprazole) in consequence of the microscopic and macroscopic evaluations. PRACTICAL APPLICATIONS: As being a member of natural products, honey has acquired fame among the studies in recent years due to its versatility as a source of food and complementary medicine. For contributing to this argument, this comprehensive study was performed and results were focused on the lower concentration of rhododendron honey thanks to its clinical potential with protecting the gastric mucosa. According to the obtained results, our suggestion came into prominence that this honey might be protecting the mucosa, better than the different concentrations of chestnut and oak honeys, by being better-absorbed through the gastric mucosa.


Assuntos
Antioxidantes/análise , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Soro/química , Úlcera Gástrica/induzido quimicamente , Animais , Produtos Biológicos , Mel , Ratos , Ratos Wistar
17.
J Plast Reconstr Aesthet Surg ; 72(10): 1640-1650, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377202

RESUMO

INTRODUCTION: Whole eye transplantation (WET) holds promise for vision restoration in devastating/disabling visual loss (congenital or traumatic) not amenable to surgical or neuroprosthetic treatment options. The eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. Anatomically and immunologically, the eye is unique due to its avascular (cornea) and highly vascular (retina) components. Our goal was to establish technical feasibility, demonstrate graft viability, and evaluate histologic changes in ocular tissues/adnexae in a novel experimental model of WET that included globe, adnexal, optic nerve (ON), and periorbital soft tissues. METHODS: Outbred Sprague-Dawley rats (n = 5) received heterotopic vascularized WET from donors. Each WET included the entire globe, adnexa, ON, and periorbital soft tissues supplied by the common carotid artery and external jugular vein. Viability and perfusion were confirmed by clinical examination, angiography and magnetic resonance imaging (MRI). Globe, adnexal, and periorbital tissues were analyzed for histopathologic changes, and the ON was examined for neuro-regeneration at study endpoint (30 days) or Banff Grade 3 rejection in the periorbital skin (whichever was earlier). RESULTS: Gross examination confirmed transplant viability and corneal transparency. Average operative duration was 64.0 ±â€¯5.8 min. Average ischemia time was 26.0 ±â€¯4.2 min. MRI revealed loss of globe volume by 36.0 ±â€¯2.8% after transplantation. Histopathology of globe and adnexal tissues showed unique and differential patterns of inflammatory cell infiltration. The ON revealed a neurodegeneration pattern. CONCLUSION: The present study is the first in the literature to establish an experimental model of WET. This model holds significant potential in investigating mechanistic pathways, monitoring strategies or developing management approaches involving ocular viability, immune rejection, and ON regeneration after WET.


Assuntos
Olho/transplante , Procedimentos Cirúrgicos Oftalmológicos/métodos , Transplante de Órgãos/métodos , Animais , Estudos de Viabilidade , Rejeição de Enxerto , Sobrevivência de Enxerto , Imageamento por Ressonância Magnética/métodos , Masculino , Modelos Teóricos , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Ratos , Ratos Sprague-Dawley , Medição de Risco , Sensibilidade e Especificidade
18.
Biomed Pharmacother ; 110: 742-747, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30554112

RESUMO

OBJECTIVE: This study aimed to investigate the protective effects of nigella sativa oil (NSO) against liver damage due to intraperitoneal (i.p.) usage of carboplatin which is commonly used as a chemotherapeutic agent. MATERIAL AND METHOD: Twenty four female Wistar-albino rats (about 200-350 grams each) were divided into 4 groups. Group 1 (n = 6) was administered 4 ml/kg intraperitoneal (i.p.) saline 48 and 24 h before. Group 2 (n = 6) was i.p. administered 4 ml/kg NSO 48 h before and 4 ml/kg saline 24 h before. Group 3 (n = 6) was i.p. administered 4 ml/kg saline 48 h before and 80 mg/kg carboplatin 24 h before. Group 4 (n = 6) was i.p. administered 4 ml/kg NSO 48 h before and 80 mg/kg carboplatin 24 h before. At the end of 48 h, all rats were sacrificed, and liver tissues were put into 10% neutral formalin. After the routine tissue follow-up, histopathological changes and collagen fiber density were evaluated with Hematoxylin-Eosin and Masson's Trichrome staining. Apoptotic index was determined with TUNEL staining. RESULTS: The degeneration in hepatocytes, fiber distribution and density around central vein and portal space was observed in the carboplatin group compared to the control and NSO groups, hepatocyte cords preserved integrity, partial degeneration in hepatocytes and decreased collagen fiber distribution around central vein was noted in the NSO-carboplatin group compared to the carboplatin group. The apoptosis was lower in the NSO-carboplatin group compare with the carboplatin group, but no statistically significant difference was found between the two groups (p = 0.449). CONCLUSION: When used NSO before carboplatin exposure, it may protect against liver damage.


Assuntos
Antineoplásicos/toxicidade , Carboplatina/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Nigella sativa , Óleos de Plantas/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Óleos de Plantas/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar
19.
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
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