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1.
Pol Merkur Lekarski ; 52(2): 240-245, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38642361

RESUMO

Platelet-rich plasma is an autologous product used in restorative medicine. It contains a high concentration of platelets, which are rich in growth factors and other biologically active substances known for their ability to stimulate regenerative processes in the body. Currently, research is being conducted into the use of platelet-rich plasma in many areas of medicine. This publication provides information on the nature, mechanism of action, therapeutic properties and application of autologous platelet-rich plasma in medicine. Furthermore, ongoing investigations explore its potential in wound healing, orthopedics, dermatology, and even in dentistry, showcasing its versatility and promising outcomes across various medical disciplines. Additionally, the safety and efficacy of platelet-rich plasma therapies are subjects of continual scrutiny, aiming to refine protocols and expand its clinical utility with robust scientific evidence. The growing interest in this regenerative approach underscores its potential as a valuable tool in modern medical practice. Platelet-rich plasma therapy represents a promising avenue for personalized medicine, offering tailored treatment approaches that capitalize on the body's own healing mechanisms to promote tissue repair and regeneration.


Assuntos
Plasma Rico em Plaquetas , Cicatrização , Humanos , Medicina Regenerativa
2.
Int J Mol Sci ; 24(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38003677

RESUMO

Due to the incidence of ovarian cancer (OC) and the limitations of available therapeutic strategies, it is necessary to search for novel therapeutic solutions. The aim of this study was to evaluate the cytotoxic effect of betulin 1 and its propynoyl derivatives 2-6 against ovarian cancer cells (SK-OV-3, OVCAR-3) and normal myofibroblasts (18Co). Paclitaxel was used as the reference compound. The propynoyl derivatives 2-6 exhibited stronger antiproliferative and cytotoxic activities compared to betulin 1. In both ovarian cancer cell lines, the most potent compound was 28-propynoylbetulin 2. In the case of compound 2, the calculated IC50 values were 0.2 µM for the SK-OV-3 cells and 0.19 µM for the OVCAR-3 cells. Under the same culture conditions, the calculated IC50 values for compound 6 were 0.26 µM and 0.59 µM, respectively. It was observed that cells treated with compounds 2 and 6 caused a decrease in the potential of the mitochondrial membrane and a significant change in cell morphology. Betulin 1, a diol from the group of pentacyclic triterpenes, has a confirmed wide spectrum of biological effects, including a significant anticancer effect. It is characterized by low bioavailability, which can be improved by introducing changes to its structure. The results showed that chemical modifications of betulin 1 only at position C-28 with the propynoyl group (compound 2) and additionally at position C-3 with the phosphate group (compound 3) or at C-29 with the phosphonate group (compound 6) allowed us to obtain compounds with greater cytotoxic activity than their parent compounds, which could be used to develop novel therapeutic systems effective in the treatment of ovarian cancer.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Triterpenos , Humanos , Feminino , Apoptose , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais
3.
Pol Merkur Lekarski ; 51(3): 271-275, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589115

RESUMO

E-cigarettes are electronic devices used to inhale aerosols generated from the vaporization of flavored liquids. Nowadays, the use of e-cigarettes has become one of the most popular alternatives to traditional smoking. The wide variety of devices and liquids makes it challenging to assess the health effects of using e-cigarettes. During the vaporization of e-liquids, toxins, carcinogens, and various other chemicals can be released and inhaled by the user. Limited data exist regarding the potential health impact of exposure to e-vapors, primarily derived from animal studies and in vitro research. The oral tissues are the first site of direct interaction with the components of the inhaled vapor. While e-cigarettes are commonly portrayed as safer alternatives to tobacco cigarettes, little is known about the short- or long-term health effects of their use. The aim of this review is to briefly present the available data regarding the impact of chemical ingredients and toxins present in e-cigarette vapors on oral cavity cells.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Animais , Saúde Bucal , Boca , Fumar
4.
Biogerontology ; 23(1): 53-64, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34923608

RESUMO

Clinical and biological assessment of the COVID-19 vaccine efficacy in the frail population is of crucial importance. The study focuses on measuring the levels of anti-SARS-CoV-2 IgG antibodies before and after BNT162b2 mRNA COVID-19 vaccination among long-term care facility (LTCF) elderly residents. We conducted a prospective, single-center, observational study among LTCF residents. The study protocol was based on three blood sample acquisitions: first taken at baseline-5 days before the first dose of the vaccine, second-20 days after the first dose, and third-12 days after the second shot of the vaccine. The comparison was made for two cohorts: patients with and without prior COVID-19 infection. The data was collected from January to March 2021. A total number of 78 LTCF residents (55 women and 23 men) aged 62-104, 85.72 ± 7.59 years (mean ± SD), were enrolled in the study. All study participants were investigated for the presence of SARS-CoV-2 anti-spike (S) protein IgG, using a chemiluminescent immunoassay. Frailty was assessed with the Clinical Frailty Scale. Among elderly COVID-19 survivors in LTCF, a single dose of vaccine significantly increased anti-SARS-CoV-2 IgG antibody levels. IgG concentration after a single and double dose was comparable, which may suggest that elderly COVID-19 survivors do not require a second dose of vaccine. For residents without a previous history of COVID-19, two doses are needed to achieve an effective serological response. The level of anti-SARS-CoV-2 IgG antibodies after vaccination with BNT162b2 mRNA COVID-19 did not correlate with the frailty and age of the studied individuals.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Fragilidade , Imunogenicidade da Vacina , Idoso , Vacina BNT162 , COVID-19/prevenção & controle , Feminino , Humanos , Assistência de Longa Duração , Masculino , Estudos Prospectivos , RNA Mensageiro , SARS-CoV-2
5.
Pol J Pathol ; 73(1): 6-13, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35848475

RESUMO

Tumor cells stimulate local angiogenesis, resulting in their further multiplication and spread. Angiogenesis is a multifaceted process in which angiopoietins parti- cipate. Angiopoietin-1 (Ang-1) through its receptor Tie2 stimulates endothelial cell survival and the maintenance of the endothelial barrier. These phenomena can support tumour growth by promoting angiogenesis. On the other hand, overproduction of Ang-1 triggers endothelium stability and can lead to angiogenesis inhibition. Because of the ambiguous role of Ang-1, we decided to determine its clinical significance in patients with resectable NSCLC. In a group of 47 patients, tumours and the adjacent non-cancerous tissues were assessed for ANG-1 mRNA expression (using Q-RT-PCR analysis) and Ang-1 concentration (by enzyme-linked immunosorbent assay) together with clinical parameters and the five-year survival rate. ANG-1 expression and Ang-1 concentration were higher in tumour-free tissue, showing no differences between histological types of NSCLC, clinical stage or grading and seemed not to determine the five-year survival. ANG-1 expression and Ang-1 concentration in tumour and tumour-free tissues in patients with NSCLC seem not to be useful as factors supporting either diagnostics or prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Angiopoietina-1/genética , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica , Prognóstico , Receptor TIE-2/genética , Receptor TIE-2/metabolismo
6.
J Appl Biomed ; 20(3): 87-97, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36218129

RESUMO

The aim of this study was to assess 17-ß-estradiol (E2) influence on sciatic nerve regeneration after injury followed by a repair with chitosan conduit in ovariectomized female rats. The study was performed in 2 groups (n = 16) of rats: OVChit - after excision of a fragment of the sciatic nerve, a chitosan conduit was implanted; OVChitE10 group - additionally to chitosan conduit, shape-memory terpolymer rods based on poly(L-lactide-co-glycolide- co-trimethylene carbonate) releasing 17-ß-estradiol for 20 weeks were implanted. The mean number of regenerating axons and mean fiber area were significantly greater in 17-ß-estradiol-treated animals. In this group, the infiltrate of leukocytes was diminished. The presence of 17-ß-estradiol receptors alpha and beta in motoneurons in the spinal cord were discovered. This may indicate the location where 17-ß-estradiol affects the regeneration of the injured nerve. Estradiol released from the terpolymer rods for 20 weeks could enhance, to some extent, sciatic nerve regeneration after injury, and diminish the inflammatory reaction. In the future, 17-ß-estradiol entrapped in terpolymer rods could be used in the repair of injured peripheral nerves, but there is a need for further studies.


Assuntos
Quitosana , Animais , Quitosana/farmacologia , Estradiol/farmacologia , Feminino , Regeneração Nervosa , Ratos , Ratos Wistar , Receptores de Estradiol , Nervo Isquiático/cirurgia
7.
Catheter Cardiovasc Interv ; 98(5): 914-922, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946190

RESUMO

OBJECTIVE: This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres. BACKGROUND: Delivery of everolimus into the arterial wall is challenging due to its low-lipophilic profile. METHODS: A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1 hour, 1,7,28, and 90-day follow-up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow-up was scheduled at 28 and 90-day. RESULTS: The study showed high-everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 ± 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time-points. CONCLUSIONS: The present study demonstrates for the first time the safety, biocompatibility, and long-term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.


Assuntos
Reestenose Coronária , Stents Farmacológicos , Nanosferas , Animais , Angiografia Coronária , Everolimo , Desenho de Prótese , Sirolimo , Stents , Suínos , Resultado do Tratamento
8.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299324

RESUMO

Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80-90%. The presence of a foreign body in the human body causes disturbances in its proper functioning. It can lead to biofilm formation on the stent surface, which may favor the development of urinary tract infections or the formation of encrustation, as well as stent fragmentation, complicating its subsequent removal. In this work, the effect of the polymeric coating containing the active substance-papaverine hydrochloride on the functional properties of ureteral stents significant for clinical practice were assessed. Methods: The most commonly clinically used polyurethane ureteral Double-J stent was selected for the study. Using the dip-coating method, the surface of the stent was coated with a poly(D,L-lactide-glycolide) (PLGA) coating containing the papaverine hydrochloride (PAP). In particular, strength properties, retention strength of the stent ends, dynamic frictional force, and the fluoroscopic visibility of the stent during X-ray imaging were determined. Results: The analysis of the test results indicates the usefulness of a biodegradable polymer coating containing the active substance for the modification of the surface of polyurethane ureteral stents. The stents coated with PLGA+PAP coating compared to polyurethane stents are characterized by more favorable strength properties, the smaller value of the dynamic frictional force, without reducing the fluoroscopic visibility.


Assuntos
Stents Farmacológicos , Papaverina/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Obstrução Ureteral/terapia , Implantes Absorvíveis , Materiais Biocompatíveis/farmacologia , Humanos , Papaverina/metabolismo , Poliuretanos/química , Obstrução Ureteral/metabolismo , Obstrução Ureteral/cirurgia
9.
Molecules ; 26(3)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33503929

RESUMO

Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise.


Assuntos
Alcinos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Necrose/tratamento farmacológico , Fosfatos/farmacologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Postepy Dermatol Alergol ; 38(3): 389-395, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34377118

RESUMO

INTRODUCTION: Chronic venous diseases (CVD), because of its chronic and progressive nature, impairs patients' quality of life (Qol). AIM: To compare the QoL in patients with primary superficial venous insufficiency at different stages before and after compression therapy (CT). MATERIAL AND METHODS: We compared the change in the QoL parameters from baseline to the end of a 6-month compression therapy. 180 subjects were enrolled. They were subdivided into 6 equal subgroups according to CEAP classes. The QoL was assessed using questionnaires, the general SF-36v2 and the disease-specific CIVIQ-20. At the beginning and after the completion of the study intervention, the severity of CVD was assessed in each patient using CEAP and VCSS. The pain intensity was assessed using the numerical rating scale. RESULTS: The CT reduced the severity of CVD, which translated into the increased size of C2 an d C5 subgroups, and reduced size of C3 and C6 subgroups. Another marker of reduced severity of CVD after CT was a significant reduction in VCSS scores in C1, and C3-C6 subgroups. A 6-month CT was associated with a significant QoL improvement in all CEAP class-based subgroups, across all individual and composite domains of SF-36v2, as well as dimensions and GIS of CIVIQ-20. Similarly, there was a significant pain reduction reported in all CEAP class-based subgroups. CONCLUSIONS: Compression therapy using ready-made compression hosiery significantly affects the quality of life in patients with chronic venous disease at all its stages, CEAP classes C1-C6.

11.
Pharm Res ; 37(5): 90, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382838

RESUMO

PURPOSE: The blood-brain barrier limits the application of idarubicin in the therapy of glioblastoma multiforme. Biodegradable, intracranial wafers with prolonged release may increase therapy efficiency. METHODS: Blank wafers, wafers containing 5% w/w and 10% w/w of idarubicin were formulated by solution casting from poly(L-lactide-co-glycolide) and poly(glycolide-co-ε-caprolactone). The following methods were used: NMR, GPC, DSC, FTIR, AFM, UV-VIS, and a viability and proliferation assay for idarubicin action (U87MG cell line). RESULTS: Wafers showed a surface with numerous immersions and hills. A lack of interactions between idarubicin and the copolymers was observed. The substance was entrapped in the matrix and released in two phases for all wafers with the appropriate bolus and maintenance dose. The burst effect was observed for all wafers, however, the biggest bolus for poly(L-lactide-co-glycolide) wafers containing 5% w/w of idarubicin was noted. The stable and steady degradation of poly(glycolide-co-ε-caprolactone) wafers containing 5% w/w of idarubicin ensures the most optimal release profile and high inhibition of proliferation. CONCLUSIONS: Copolymer wafers with idarubicin are an interesting proposition with great potential for the local treatment of glioblastoma multiforme. The release rate and dose may be regulated by the amount and kind of wafers for various effects.


Assuntos
Portadores de Fármacos/síntese química , Glioblastoma/tratamento farmacológico , Idarubicina/uso terapêutico , Polímeros/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular , Liberação Controlada de Fármacos , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tecnologia Farmacêutica/métodos
12.
Saudi Pharm J ; 28(3): 290-299, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194330

RESUMO

PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm. The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.

13.
Rep Pract Oncol Radiother ; 25(4): 579-585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494232

RESUMO

AIM: This work is focused on the Monte Carlo microdosimetric calculations taking into account the influence of the AuNPs' shape, size and mass concentration on the radiation dose enhancement for the high-energy 6 MV and 18 MV X-ray therapeutic beams from a medical linac. BACKGROUND: Due to a high atomic number and the photoelectric effect, gold nanoparticles can significantly enhance doses of ionizing radiation. However, this enhancement depends upon several parameters, such as, inter alia, nanoparticles' shape etc. METHOD: The simulated system was composed of the therapeutic beam, a water phantom with the target volume (with and without AuNPs) located at the depth of the maximum dose, i.e. at 1.5 cm for the 6 MV beam and at 3.5 cm for the 18 MV one. In the study the GEANT4 code was used because it makes it possible to get a very short step of simulation which is required in case of simulating the radiation interactions with nanostructures. RESULTS: The dependence between the dose increase and the mass concentration of gold was determined and described by a simple mathematical formula for three different shapes of gold nanoparticles - two nanorods of different sizes and a flat 2D structure. The dose increase with the saturation occurring with the increasing mass concentration of gold was observed. CONCLUSIONS: It was found that relatively large cylindrical gold nanoparticles can limit the increase of the dose absorbed in the target volume much more than the large 2D gold nanostructure.

14.
Bioorg Chem ; 87: 613-628, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30947097

RESUMO

Betulin derivatives exhibit an antiproliferative activity and have been tested for many cancer cell lines. This paper describes a new series of 3-phosphate derivatives of betulin bearing different substituents at C28 position. The synthesized compounds were tested in vitro for their antiproliferative effect against human leukemia (MV-4-11 and CCRF/CEM), lung carcinoma (A549), prostate cancer (DU 145), melanoma (Hs 294T) cell lines, and murine leukemia P388. To explore the possible mechanism of anticancer activity for the most in vitro active compounds (4, 5, 7 and 8) and betulin, molecular docking was performed to the binding sites of potential anticancer targets, described for the various triterpene derivatives, including topoisomerase I and II, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGFR), transcription factor NF-κB, anti-apoptotic protein Bcl-2 and peroxisome proliferator-activated receptor (PPARγ). According to the results of the docking, the best fit to the binding pocket of PPARγ was shown by compound 4.


Assuntos
Antineoplásicos/farmacologia , Simulação de Acoplamento Molecular , Fosfatos/farmacologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fosfatos/síntese química , Fosfatos/química , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/química , Células Tumorais Cultivadas
15.
Pharm Res ; 33(12): 2967-2978, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27628625

RESUMO

PURPOSE: Estradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined. METHODS: The extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope. RESULTS: A stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods. CONCLUSIONS: Shape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.


Assuntos
Estradiol/administração & dosagem , Nanotubos/química , Doenças Neurodegenerativas/tratamento farmacológico , Poliésteres/química , Animais , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estradiol/química , Estradiol/farmacocinética , Feminino , Hidrólise , Ratos Wistar , Propriedades de Superfície , Distribuição Tecidual
16.
Postepy Hig Med Dosw (Online) ; 70(0): 1404-1408, 2016 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28100848

RESUMO

INTRODUCTION: A relatively new approach in treatment of malignant melanoma is the use of betulin and its synthetic derivatives that have anticancer properties. The aim of the study was to determine the effect of an acetylenic derivative of betulin, 28-O-propynoylbetulin, on cell growth and apoptosis induction in human melanotic and amelanotic melanoma cells. MATERIALS AND METHODS: The A2058 and C32 cell lines were incubated with 28-O-propynoylbetulin (working solutions from 0.1 to 10 µg/ml). To evaluate cell proliferation, a sulforhodamine B based assay was conducted. In order to elucidate the early stages of apoptosis in both melanoma cell lines, caspase-3 activity was evaluated. RESULTS: The administration of 28-O-propynoylbetulin at a concentration equal to or less than 1 µg/ml did not cause a statistically significant change in the cell proliferation in either melanoma cell line (compared to control, p>0.05). Higher concentrations of the compound (3 and 10 µg/ml) inhibited the cell growth (in comparison to control, p<0.05). These results corresponded with caspase-3 activity results that revealed an increase of enzyme activity after 24-hour incubation with 3 and 10 µg/ml of the compound (compared to control, p<0.05). DISCUSSION: The study revealed that 28-O-propynoylbetulin may have diverse effects on melanoma cells and could be a strong inhibitor of cell growth (C32 cells) or exert a more potent proapoptotic effect (A2058 cells). These findings support the possibility of the use of EB5 in different antimelanoma approaches.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Melanoma/tratamento farmacológico , Triterpenos/farmacologia , Adulto , Caspase 3/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Melanoma/metabolismo , Melanoma/fisiopatologia , Pessoa de Meia-Idade
17.
Pol J Pathol ; 66(3): 231-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26619101

RESUMO

Chronic hepatitis C (CHC) is accompanied by numerous metabolic disorders, partially associated with altered adipokine system regulation. Omentin (intelectin-1) is a novel adipokine known to play a pivotal role in metabolic regulation in CHC. In a group of 63 CHC patients (29 men/34 women) infected with genotype 1b, aged 6.6 ± 14.6 years, serum omentin levels and its gene expression in liver tissue were examined and their association with metabolic and histopathological features was assessed. Serum omentin levels were significantly higher in CHC patients compared to controls (p < 0.001), regardless of sex, body mass index (BMI), insulin sensitivity and lipid concentrations. There was no correlation between serum omentin and omentin hepatic expression. Neither parameter was associated with any histological features. Serum omentin in non-obese CHC patients seems not to be related to metabolic disorders or liver pathology. Omentin hepatic expression shows no relationship with either serum omentin levels or histopathological features. This suggests different mechanisms regulating circulating omentin concentration and omentin hepatic expression in CHC.


Assuntos
Citocinas/biossíntese , Hepatite C Crônica/metabolismo , Lectinas/biossíntese , Adulto , Idoso , Citocinas/análise , Feminino , Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/biossíntese , Hepatite C Crônica/patologia , Humanos , Lectinas/análise , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
18.
Toxicol Appl Pharmacol ; 280(1): 36-41, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25038314

RESUMO

The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead. The population consisted of two randomly divided groups of healthy male volunteers exposed to lead. Workers in the first group (reference group) were not administered any antioxidants, while workers in the second group (CAR group) were treated orally with 10mg of beta-carotene once a day for 12weeks. Biochemical analysis included measuring markers of lead-exposure and oxidative stress in addition to the levels and activities of selected antioxidants. After treatment, levels of malondialdehyde, lipid hydroperoxides and lipofuscin significantly decreased compared with the reference group. However, the level of glutathione significantly increased compared with the baseline. Treatment with beta-carotene also resulted in significantly decreased glutathione peroxidase activity compared with the reference group, while the activities of other glutathione-related enzymes and of superoxide dismutase were not significantly changed. However, the activities of glucose-6-phosphate dehydrogenase and catalase, as well as the level of alpha-tocopherol, were significantly higher after treatment compared with the baseline. Despite controversy over the antioxidant properties of beta-carotene in vivo, our findings showed reduced oxidative stress after beta-carotene supplementation in chronic lead poisoning.


Assuntos
Antioxidantes/metabolismo , Glutationa/metabolismo , Intoxicação por Chumbo/tratamento farmacológico , Doenças Profissionais/tratamento farmacológico , Estresse Oxidativo/fisiologia , beta Caroteno/uso terapêutico , Adulto , Humanos , Intoxicação por Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Estresse Oxidativo/efeitos dos fármacos , Adulto Jovem , beta Caroteno/farmacologia
19.
Acta Pol Pharm ; 71(6): 1023-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25745774

RESUMO

Bioresorbable, aliphatic polyesters are known in medicine where serve as orthopedic devices (e.g., rods, pins and screws) or sutures and staples in wound closure. Moreover, such materials are extensively stud- ied as scaffolds--three-dimensional structures for tissue engineering but also drug delivery systems (DDS). The aim of this study was to determine the release profile of paclitaxel, one of the anti-inflammatory, antiprolifera- tive and anti-restenotic agent, from biocompatible copolymer of L-lactide and ε-caprolactone that seems to be very attractive especially for minimally invasive surgery due to its potential shape-memory property. The influ- ence of drug on copolymer hydrolytic degradation was also analyzed. Three types of matrices (3%, 5% of PTX and without drug) were prepared by solvent-casting method and degraded in vitro. The physicochemical changes of copolymer were analyzed by means of nuclear magnetic resonance spectroscopy (NMR), gel per- meation chromatography (GPC) and differential scanning calorimetry (DSC). The amount of drug released into media was monitored with the use of high-pressure liquid chromatography (HPLC). Similar drug release pro- files were obtained for matrices with paclitaxel. The drug-containing matrices degraded slightly slower than drug free matrices, regardless PTX content. Results of this work may be helpful in designing new bioresorbable paclitaxel delivery system applied in anti-cancer therapy or drug-eluting stents technology.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Paclitaxel/administração & dosagem , Poliésteres/química , Varredura Diferencial de Calorimetria , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Espectroscopia de Ressonância Magnética
20.
Med Pr ; 65(3): 309-16, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25230559

RESUMO

BACKGROUND: Oxidative stress is involved in lead toxicity. This suggests that some antioxidants may play a role in the treatment of lead poisoning. In the light of this, the aim of the study was to determine whether beta-carotene administration reduces oxidative stress and homocysteine level in workers chronically exposed to lead. MATERIAL AND METHODS: The exposed population included healthy male workers exposed to lead who were randomly divided into 2 groups (mean blood lead level ca. 44 microg/dl). Workers in the 1st group (N = 49, reference group) had no antioxidants, drugs, vitamins or dietary supplements administered, while workers in the 2nd group (N = 33) had beta-carotene administered in a dose of 10 mg per day for 12 weeks. Biochemical analysis included markers of lead-exposure and the level of malondialdehyde (MDA), an oxidative stress biomarker. We also measured the level of homocysteine (Hcy) and thiol groups as well as the activity of superoxide dismutase (SOD) and its isoenzyme EC-SOD in serum. RESULTS: After supplementation, the level of MDA significantly decreased, compared to baseline, by 16%, and to the reference group. When compared to the reference group, Hcy level was also significantly decreased. However, the level of thiol groups was significantly higher after supplementation with beta-carotene compared to the reference group. Analogically, the activity of SOD and EC-SOD was significantly higher compared to the baseline and to the reference group. CONCLUSIONS: Despite some controversies over antioxidant properties of beta-carotene, our results indicate that its antioxidant action could provide some beneficial effects in lead poisoning independent of chelation.


Assuntos
Homocisteína/sangue , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/tratamento farmacológico , Doenças Profissionais/sangue , Doenças Profissionais/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , beta Caroteno/uso terapêutico , Antioxidantes/uso terapêutico , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Polônia , Compostos de Sulfidrila/sangue , Superóxido Dismutase/sangue
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