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1.
Artigo em Inglês | MEDLINE | ID: mdl-33179265

RESUMO

INTRODUCTION: We aimed to give a global overview of trends in access to sexual and reproductive health and rights (SRHR) during the coronavirus disease 2019 (COVID-19) pandemic and what is being done to mitigate its impact. MATERIAL AND METHODS: We performed a descriptive analysis and content analysis based on an online survey among clinicians, researchers, and organizations. Our data were extracted from multiple-choice questions on access to SRHR services and risk of SRHR violations, and written responses to open-ended questions on threats to access and required response. RESULTS: The survey was answered by 51 people representing 29 countries. Eighty-six percent reported that access to contraceptive services was less or much less because of COVID-19, corresponding figures for surgical and medical abortion were 62% and 46%. The increased risk of gender-based and sexual violence was assessed as moderate or severe by 79%. Among countries with mildly restrictive abortion policies, 69% had implemented changes to facilitate access to abortion during the pandemic, compared with none among countries with severe restrictions (P < .001), 87.5% compared with 46% had implemented changes to facilitate access to contraception (P = .023). The content analysis showed that (a) prioritizations in health service delivery at the expense of SRHR, (b) lack of political will, (c) the detrimental effect of lockdown, and (d) the suspension of sexual education, were threats to SRHR access (theme 1). Requirements to mitigate these threats (theme 2) were (a) political will and support of universal access to SRH services, (b) the sensitization of providers, (c) free public transport, and (d) physical protective equipment. A contrasting third theme was the state of exception of the COVID-19 pandemic as a window of opportunity to push forward women's health and rights. CONCLUSIONS: Many countries have seen decreased access to and increased violations of SRHR during the COVID-19 pandemic. Countries with severe restrictions on abortion seem less likely to have implemented changes to SRHR delivery to mitigate this impact. Political will to support the advancement of SRHR is often lacking, which is fundamental to ensuring both continued access and, in a minority of cases, the solidification of gains made to SRHR during the pandemic.

2.
Water Sci Technol ; 81(3): 421-435, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32385196

RESUMO

A novel compound was synthesized by the reaction of the amino group of the chitosan with the formyl group of pyrano[3,2-c]quinoline-3-carboxaldehyde moiety, which produced chitosan modified with a Schiff base (chitosan Schiff base). The structure of the newly prepared composite was elucidated. Chitosan Schiff base was used to remove the textile anionic remazol red (RR) dye from wastewater. The kinetic data and adsorption isotherm were best fitted by the pseudo-second-order kinetic model and the Freundlich isotherm, respectively. Thermodynamic parameters were calculated. Chitosan Schiff base resulted in 100% removal of carcinogenic dye at 2 min only with qm 344.8 mg/g, and may do the same for other anionic reactive dyes, thus avoiding secondary pollution.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Corantes , Concentração de Íons de Hidrogênio , Cinética , Têxteis , Águas Residuárias
3.
Anesth Analg ; 131(1): 298-306, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31990732

RESUMO

BACKGROUND: Anti-inflammatory corticosteroids are a common treatment for different conditions involving chronic pain and inflammation. Clinically used steroids target the glucocorticoid receptor (GR) for its anti-inflammatory effects. We previously reported that GR in sensory neurons may play central roles in some pain models and that GR immunoreactivity signal in dorsal root ganglia (DRG) decreased after local inflammation of the DRG (a model of low back pain). In the current study, we aimed to determine if similar changes in GR signal also exist in a skin inflammation model, the complete Freund's adjuvant (CFA) model (a model of peripheral inflammatory pain), in which the terminals of the sensory neurons rather than the somata are inflamed. METHODS: A low dose of CFA was injected into the hind paw to establish the peripheral inflammation model in Sprague-Dawley rats of both sexes, as confirmed by measurements of behavior and paw swelling. Immunohistochemical and western blotting techniques were used to determine the expression pattern of the GR in the inflamed hind paw and the DRGs. Plasma corticosterone levels were measured with radioimmunoassay. RESULTS: The immunohistochemical staining revealed that GR is widely expressed in the normal DRG and skin tissues. Paw injection with CFA caused upregulation of the GR in the skin tissue on postinjection day 1, mostly detected in the dermis area. However, paw inflammation significantly reduced the GR signal in the L5 DRG 1 day after the injection. The GR downregulation was still evident 14 days after CFA inflammation. On day 1, western blotting confirmed this downregulation and showed that it could also be observed in the contralateral L5 DRG, as well as in the L2 DRG (a level which does not innervate the paw). Plasma corticosterone levels were elevated in both sexes on day 14 after CFA compared to day 1, suggesting autologous downregulation of the GR by corticosterone may have contributed to the downregulation observed on day 14 but not day 1. CONCLUSIONS: There are distinctive patterns of GR activation under different pain conditions, depending on the anatomical location. The observed downregulation of the GR in sensory neurons may have a significant impact on the use of steroids as treatment in these conditions and on the regulatory effects of endogenous glucocorticoids.


Assuntos
Modelos Animais de Doenças , Hiperalgesia/metabolismo , Receptores de Glucocorticoides/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Feminino , Adjuvante de Freund/toxicidade , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/efeitos dos fármacos
4.
Int Immunopharmacol ; 80: 106131, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981960

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. METHOD: To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R. RESULTS: Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1ß, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation. CONCLUSION: We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.


Assuntos
Curcumina/farmacologia , Fumarato de Dimetilo/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Curcumina/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Falência Hepática Aguda/imunologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
5.
Environ Sci Pollut Res Int ; 27(3): 3401-3412, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31840221

RESUMO

Mercury (Hg) is a heavy metal toxicant, causing several adverse reactions to animals and humans including reproductive dysfunction. The potential protective role of Ziziphus spina-christi leaf extract (ZSCLE) against testicular impairments associated with mercury chloride (HgCl2) exposure in rats was investigated in the current study. Four experimental groups were employed as follows (n = 7): group I served as control, group II was gavaged with ZSCLE (300 mg/kg), group III was administered with HgCl2 (0.4 mg/kg), and group IV was preadministered with ZSCLE 1 h before HgCl2. All groups were treated daily for 28 days. The exposure to HgCl2 caused a marked increase in Hg concentration in the testicular tissue, which was accompanied with a decrease in testis index. A reproductive impairment was recorded following HgCl2 exposure as verified through the decrease in levels of testosterone, luteinizing, and follicle-stimulating hormones. HgCl2 was found to enhance the development of oxidative damage in the testicular tissue as presented by the imbalance between pro-oxidants and antioxidant molecules. In addition, excessive release of tumor necrosis factor-α and interleukin-1ß was recorded in response to HgCl2 intoxication. Furthermore, a disturbance in the apoptotic proteins in favor of the pro-apoptotic proteins was also observed following HgCl2 intoxication. However, ZSCLE administration along with HgCl2 abolished significantly the molecular, biochemical, and histopathological alterations induced by HgCl2 intoxication. Our findings suggest that ZSCLE could be used to mitigate reproductive dysfunction associated with HgCl2 exposure.


Assuntos
Substâncias Perigosas/toxicidade , Cloreto de Mercúrio/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ziziphus , Animais , Antioxidantes , Masculino , Mercúrio , Estresse Oxidativo , Ratos , Testículo/efeitos dos fármacos , Testículo/fisiologia
6.
Environ Sci Pollut Res Int ; 26(31): 31675-31684, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31482528

RESUMO

Oxidative stress is an imbalance between free radicals and antioxidants which leads to reactive oxygen species (ROS) production in cells. Reactive oxygen species contains oxygen radicals that easily react with other molecules in the biological system. For decades, lead acetate (Pb(C2H3O2)2) is used as an additive for many widely used chemical products such as insecticides, hair dyes, and cosmetics; however, contact with lead acetate may irritate skin, eyes, and mucous membranes.In the present study, the antioxidant and anti-inflammatory effect of using ferulic acid to inhibit lead acetate-induced toxicity in rats is investigated. Lead acetate was orally given at a dose of 20 mg/kg body weight for 10 days, either alone or with ferulic acid at dose 25 mg/kg. Serum luteinizing hormone (LH), total testosterone, and follicle-stimulating hormone (FSH) levels were measured. Also, reactive oxygen species (ROS), lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase (CAT) activities were determined. In addition, histopathological changes of testes and kidney were examined. Results showed that administration of lead acetate induced oxidative stress through attenuation of luteinizing hormone, total testosterone, and follicle-stimulating hormone levels in serum. Moreover, the kidney and testes of lead acetate-treated animals exhibited elevation of ROS level, lipid peroxide levels, as well as lysosomal enzyme activity such acid phosphatase and N-acetyl-ß-glucosminidase. DNA fragmentation and histological changes were also observed in lead acetate-treated group. In contrast, ferulic acid treatment reduced the deleterious effects induced by lead acetate in both testes and kidney tissues. These results illustrated that ferulic acid has a protective action against toxicity caused by lead acetate in rats. In conclusions, ferulic acid may have future therapeutic relevance in the prevention of lead acetate-induced testicular and renal toxicity in rats.


Assuntos
Antioxidantes/metabolismo , Ácidos Cumáricos/análise , Dano ao DNA/efeitos dos fármacos , Radicais Livres/metabolismo , Rim/efeitos dos fármacos , Chumbo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/sangue , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Testículo/efeitos dos fármacos , Animais , Ácidos Cumáricos/química , Radicais Livres/química , Hormônio Luteinizante/química , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/química
7.
J Pharm Sci ; 108(6): 1923-1933, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30684539

RESUMO

With the significant advances made in nanotechnology, research efforts focused on developing novel drug delivery platforms that can overcome the multitude of challenges encountered in ophthalmic drug delivery. Surface active agents (SAAs) have been extensively used for the formulation of many of the dosage forms targeting ocular tissues. Novel ophthalmic carriers utilizing SAAs were broadly classified into particulate, vesicular, and controlled release drug delivery systems. Depending on their physicochemical properties, SAAs can perform a variety of roles ranging from wetting agents, emulsifiers, stabilizers, charge inducers, solubilizers, antimicrobial agents, corneal permeation enhancers, and gelling agents. Nevertheless, their use is limited by their potential toxicity and possible interactions with other formulation ingredients. This review provides a comprehensive analysis of the different functional roles of SAAs in novel ophthalmic drug delivery platforms, their mechanism of action, and limitations that need to be considered during formulation to maximize their potential benefit. Understanding the mechanisms by which they perform their different roles and the possible interactions between SAAs and other formulation ingredients can help orientate the choice of formulators toward the SAA most suitable for the intended ocular application at a concentration that is both safe and effective.


Assuntos
Oftalmopatias/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Tensoativos/farmacologia , Administração Oftálmica , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Córnea/metabolismo , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Soluções Oftálmicas/farmacocinética , Permeabilidade/efeitos dos fármacos , Veículos Farmacêuticos/química , Veículos Farmacêuticos/farmacologia , Tensoativos/química , Distribuição Tecidual
8.
Front Cell Neurosci ; 12: 453, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524245

RESUMO

Low back pain, a leading cause of disability, is commonly treated by epidural steroid injections that target the anti-inflammatory glucocorticoid receptor (GR). However, their efficacy has been controversial. All currently used epidural steroids also activate the pro-inflammatory mineralocorticoid receptor (MR) with significant potency. Local inflammation of the dorsal root ganglia (DRG), a rat model of low back pain, was used. This model causes static and dynamic mechanical allodynia, cold allodynia and guarding behavior (a measure of spontaneous pain), and activates the MR, with pro-nociceptive effects. In this study, effects of local Dexamethasone (DEX; a glucocorticoid used in epidural injections), and eplerenone (EPL; a second generation, more selective MR antagonist) applied to the DRG at the time of inflammation were examined. Mechanical and spontaneous pain behaviors were more effectively reduced by the combination of DEX and EPL than by either alone. The combination of steroids was particularly more effective than DEX alone or the model alone (3-fold improvement for mechanical allodynia) at later times (day 14). Immunohistochemical analysis of the GR in the DRG showed that the receptor was expressed in neurons of all size classes, and in non-neuronal cells including satellite glia. The GR immunoreactivity was downregulated by DRG inflammation (48%) starting on day 1, consistent with the reduction of GR (57%) observed by Western blot, when compared to control animals. On day 14, the combination of DEX and EPL resulted in rescue of GR immunoreactivity that was not seen with DEX alone, and was more effective in reducing a marker for satellite glia activation/neuroinflammation. The results suggest that EPL may enhance the effectiveness of clinically used epidural steroid injections, in part by enhancing the availability of the GR. Thus, the glucocorticoid-mineralocorticoid interactions may limit the effectiveness of epidural steroids through the regulation of the GR in the DRG.

9.
Biomed Pharmacother ; 106: 1490-1498, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30119224

RESUMO

This study was aimed at investigating the possible protective mechanism of royal jelly (RJ) against hepatotoxicity induced by cadmium chloride (CdCl2). The study included four groups: the control group received saline (0.9% sodium chloride), CdCl2 group received 6.5 mg/kg CdCl2 for seven days, RJ group received 85 mg/kg standardized RJ containing 6% 10-hydroxy-2-decenoic acid equivalent to 250 mg crude RJ, and finally, the fourth group received RJ 2 h before CdCl2 injection daily for 7 days. Oxidant/antioxidant markers of liver function estimation and histopathology were determined. The results revealed that RJ significantly ameliorated the hepatotoxic side effects of Cd. Furthermore, RJ inhibited oxidative stress, inflammation, and hepatic tissue injury; normalized enzymatic and nonenzymatic antioxidant molecules; and enhanced nuclear-related factor-2 (Nrf-2) expression. Our results provide new insights into the hepatoprotective property of RJ and revealed that RJ prevented hepatic injury, oxidative stress, and inflammation by upregulating Nrf2 and the anti-apoptotic protein Bcl-2. Hence, RJ can be used as a hepatoprotective agent against the toxic effects of CdCl2.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cloreto de Cádmio , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ácidos Graxos/farmacologia , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
10.
Int J Pharm ; 540(1-2): 40-49, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29408473

RESUMO

Lung cancer is the major cause of cancer-related death worldwide. Curcumin attracted attention due to its promising anti-cancer properties, however its poor aqueous solubility and bioavailability have to be overcome. In the current study curcumin is encapsulated in krill lipids-based liposomes (marinosomes) to develop a potential anticancer therapy from low-cost and readily available nutraceuticals. Reflux followed by thin drug-lipid film method is used successfully to incorporate the drug into the liposomal membrane at high encapsulation efficiency (EE). The curcumin-loaded marinosomes (CURMs) showed a powerful antioxidant activity (EC50 ≒ 4 µg/mL). Additionally, CURMs exhibited good physicochemical and oxidative stability after eight weeks' storage at 4 °C. Furthermore, CURMs exhibited sustained release of about 30% of their curcumin content under in vitro culture conditions at 37 °C after 72 h. Consequently, CURMs showed its maximum cytotoxic effect (IC50; 11.7 ±â€¯0.24 µg/ml) after incubation for 72 h against A549 lung cancer cells. Additionally, CURMs inhibited the proliferation of HUVECs in a dose-dependent manner with IC50 of 2.64 ±â€¯0.21 µg/ml after incubation for 24 h. The current study presents the CURM as a favorable in vitro drug delivery system to target cancer disease.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Curcumina/farmacologia , Euphausiacea/química , Ácidos Graxos Insaturados/química , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas , Células A549 , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/toxicidade , Proliferação de Células/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/química , Curcumina/toxicidade , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Ácidos Graxos Insaturados/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Concentração Inibidora 50 , Lipossomos , Neoplasias Pulmonares/patologia , Nanomedicina , Oxirredução , Tecnologia Farmacêutica/métodos , Temperatura , Fatores de Tempo
11.
Water Sci Technol ; 76(9-10): 2719-2732, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29168712

RESUMO

Adsorption capacity of three antimicrobial terephthaloyl thiourea cross-linked chitosan hydrogels for Congo red dye removal from its aqueous solution has been investigated for the first time in this work. These hydrogels were prepared by reacting chitosan with various amounts of terephthaloyl diisothiocyanate cross-linker. The effect of the hydrogel structural variations and several dye adsorption processing parameters to achieve the best adsorption capacity were investigated. The hydrogels' structural variations were obtained by varying their terephthaloyl thiourea moieties content. The processing variables included initial concentration of the dye solution, temperature and time of exposure to the dye. The adsorption kinetics and isotherms showed that the sorption processes were better fitted by the pseudo-second-order equation and the Langmuir equation, respectively. On the basis of the Langmuir analysis Congo red dye gave the maximum sorption capacity of 44.248 mg/g. The results obtained confirmed that the sorption phenomena are most likely to be controlled by chemisorption process. The adsorption reaction was endothermic and spontaneous according to the calculated results of adsorption thermodynamics.


Assuntos
Anti-Infecciosos/química , Quitosana/química , Corantes/química , Vermelho Congo/química , Hidrogéis/química , Tioureia/química , Poluentes Químicos da Água/química , Adsorção , Anti-Infecciosos/isolamento & purificação , Reagentes para Ligações Cruzadas/química , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Termodinâmica , Poluentes Químicos da Água/isolamento & purificação
12.
Biol Pharm Bull ; 40(6): 815-823, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566625

RESUMO

The trans platinum-chloroquine diphosphate dichloride (PtCQ) is a new type of antimalarial drug used to fight parasites resistant to traditional drugs. PtCQ is synthesized by mixing platinum and chloroquine diphosphate (CQ). This study examines two efficient methods for forming a nanodrug, PtCQ-loaded liposomes, for use as a potential antimalarial drug-delivery system: the thin drug-lipid film method to incorporate the drug into a liposomal membrane, and a remote-loading method to load the drug into the interior of a cationic liposome. The membranes accordingly comprised PEGylated neutral or cationic liposomes. PtCQ was efficiently loaded into PEGylated neutral and cationic liposomes using the thin drug-lipid film method (encapsulation efficiency, EE: 76.1±6.7% for neutral liposomes, 1 : 14 drug-to-lipid weight ratio; 70.4±9.8% for cationic liposomes, 1 : 14 drug-to-lipid weight ratio). More PtCQ was loaded into PEGylated neutral liposomes using the remote-loading method than by the thin drug-lipid film method and the EE was maximum (96.1±4.5% for neutral liposomes, 1 : 7 (w/w)). PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids (0-20 mol%; EE: 96.9-92.3%) using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months' storage at 4°C, and further exhibited little release under in vitro culture conditions at 37°C for 72 h. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the malaria parasite.


Assuntos
Antimaláricos/química , Cloroquina/análogos & derivados , Sistemas de Liberação de Medicamentos , Platina/química , Polietilenoglicóis/química , Cloroquina/química , Liberação Controlada de Fármacos , Resistência a Medicamentos , Lipídeos/química , Lipossomos , Malária , Plasmodium falciparum
13.
Int J Pharm ; 526(1-2): 271-279, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28479519

RESUMO

Thromboprophylaxis and anticoagulant therapy face serious medical challenges in terms of how crucial it is to maintain therapeutic activity of the anticoagulant agent over the required period of time. Failure to do so will lead to an increased risk of clot propagation if a subtherapeutic drug level is reached. On the other hand, higher-than intended anticoagulation levels might lead to an enhanced risk of hemorrhagic complications. Nanocomplexes (NCs) for the controlled delivery of the antithrombotic Enoxaparin (Enox) with dextran sulfate (DS) and chitosan (CS) were formulated, in an attempt to circumvent therapeutic and compliance challenges associated with the prolonged administration of the current dosage form. Using polyelectrolyte complexation method, various fabrication and formulation parameters were tested. Assessment of ex-vivo stability of selected formulae in rat serum was done prior to determination of their pharmacokinetic profile. High EE% was achieved in all systems prepared. In absence of DS, target size was obtained when 0.54mg/mL CS at an initial pH of 5 and Enox to CS mass ratio of 1:2.5 were employed at room temperature. These parameters were shifted to new optima upon introduction of DS. The anticoagulant activity of NCs (in absence/presence of DS) was significantly sustained compared to the market product (135 and >144h versus 5h, respectively).


Assuntos
Quitosana/química , Sulfato de Dextrana/química , Portadores de Fármacos/química , Enoxaparina/administração & dosagem , Animais , Anticoagulantes/administração & dosagem , Química Farmacêutica , Ratos
14.
Drug Deliv ; 24(1): 243-251, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28156170

RESUMO

Pulmonary bed can retain microparticles (MP) larger than their capillaries' diameter, hence we offer a promising way for lung passive targeting following intravenous (IV) administration. In this study, enoxaparin (Enox)-albumin microspheres (Enox-Alb MS) were, optimally, developed as lung targeted sustained release MP for IV use. Lung tolerability and targeting efficiency of Enox-Alb MS were tested, and the pharmacokinetic profile following IV administration to albino rats was constructed. In vivo studies confirmed high lung targeting efficiency of Enox-Alb MS with lack of potential tissue toxicity. The anticoagulant activity of the selected Alb MS was significantly sustained for up to 38 h compared to 5 h for the market product. Alb MS are promising delivery carriers for controlled and targeted delivery of Enox to the lungs for prophylaxis and treatment of pulmonary embolism.


Assuntos
Anticoagulantes/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Enoxaparina/administração & dosagem , Pulmão/efeitos dos fármacos , Administração Intravenosa/métodos , Albuminas/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Masculino , Microesferas , Ratos
16.
BMC Complement Altern Med ; 16(1): 434, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27821159

RESUMO

BACKGROUND: Schistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni. METHODS: The schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining. RESULTS: Typical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue. CONCLUSION: These data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.


Assuntos
Fabaceae/química , Cirrose Hepática/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Catalase/genética , Catalase/metabolismo , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/parasitologia , Masculino , Camundongos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/genética , Esquistossomose mansoni/metabolismo , Esquistossomose mansoni/parasitologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo
17.
J Anesth Perioper Med ; 3(4): 177-184, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28956026

RESUMO

AIM OF REVIEW: Low back pain is a major health problem in United States and worldwide. In this review, we aim to show that mineralocorticoid receptor (MR) activation has a critical role in the initiation of immune and inflammatory responses, which in turn can impact the effectiveness of the currently used steroids for epidural injections in low back pain management since most steroids activate MR in addition to the primary target, glucocorticoid receptor (GR). Moreover, we would like to determine some of the benefits of blocking the MR-induced negative effects. Overall, we propose a novel therapeutic approach for low back pain management by using a combination of a MR antagonist and a GR agonist in the epidural injections. METHOD: We will first introduce the societal cost of low back pain and discuss how epidural steroid injections became a popular treatment for this condition. We will then describe several preclinical models used for the study of low back pain conditions and the findings with respect to the role of MR in the development of inflammatory low back pain. RECENT FINDINGS: MR has pro-inflammatory effects in many tissues which can counteract the anti-inflammatory effects induced by GR activation. Blocking MR using the selective MR antagonist eplerenone can reduce pain and sensory neuron excitability in experimental models of low back pain. Moreover, combining the MR antagonist with clinically used steroids is more effective in reducing pain behaviors than using the steroids alone. SUMMARY: MR antagonists are promising candidates to increase the effectiveness of currently used steroids. Since the activation of the MR is evident in preclinical models of low back pain, blocking its deleterious effects can be beneficial in managing inflammatory pain conditions.

18.
Neural Regen Res ; 11(11): 1797-1803, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28123424

RESUMO

Lead (Pb) is one of the most common environmental toxicants, exposure to which can cause significant neurotoxicity and an associated decline in brain function. This study investigated the possible neuroprotective role of Indigofera oblongifolia leaf methanolic extract (IOLME) against lead-induced neurotoxicity. Rats were intraperitoneally injected with lead acetate, with or without IOLME (intragastric administration for 5 days), and the neuroprotective effect of IOLME was assessed by measuring the lead concentration, redox status (lipid peroxidation, nitric oxide and glutathione), enzymatic antioxidant activities (superoxide dismutase, catalase, glutathione peroxidase and reductase), PCR assays of apoptosis markers (Bax and Bcl-2) and histopathology of the brain. The increases in the lipid peroxidation, nitric oxide, and apoptosis, the decreases in the glutathione level and the activity of antioxidant enzymes, and the altered histology of the brain induced by lead acetate were mitigated in the brain of rats pre-treated with IOLME. These findings indicate that IOLME has beneficial effects and it mitigates lead acetate-induced neurotoxicity via its antioxidant and anti-apoptotic activities.

19.
Drug Deliv ; 23(8): 2661-2667, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26056721

RESUMO

Low molecular weight heparins (LMWHs), the anticoagulant drug of choice in many indications, had been suggested as novel drug treatment for a range of diseases. Their superior pharmacokinetic properties compared to unfractionated heparin (UFH), motivated scientists to explore new delivery systems for improved therapeutic outcomes. Micro- and nano-carriers, with the versatile nature and characteristics of materials used for their fabrication, are able to surmount the challenges opposed by their native structures. The present review discusses the recent perspectives on the development of micro- and nano-particulate vectors for the delivery of LMWHs through various routes. Special focus on the application of the suggested systems, their characterization and the achieved improved bioavailability will be given throughout the review.


Assuntos
Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Nanopartículas/química , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Heparina de Baixo Peso Molecular/química , Humanos
20.
Colloids Surf B Biointerfaces ; 69(2): 225-31, 2009 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19157802

RESUMO

Pluronic F68 is a nonionic, thermogelling block copolymer showing a high dehydration resistance during autoclaving due to its high cloud point (>100 degrees C). Tween 80 (with cloud point of 72.5 degrees C), is a polyoxyethylene-based cosurfactant, susceptible to temperature because of a decrease in its solubility by temperature increase. This study was done to explore whether or not, when compared with Tween 80, Pluronic F68 could be used blindly as a suitable cosurfactant for the preparation of terminally sterilized ocular submicron emulsions containing a lipid soluble drug, prednisolone acetate (PA). Various oils of variable viscosities were also tried. The results proved that no prediction can be made based on previously known physico-chemical properties alone and that emulsion stability depends on the contribution of the various emulsion components including: oil, surfactant and cosurfactant, in addition to the drug properties.


Assuntos
Poloxâmero/química , Polissorbatos/química , Prednisolona/análogos & derivados , Tensoativos/química , Animais , Óleo de Rícino/química , Fenômenos Químicos , Estabilidade de Medicamentos , Emulsões , Olho , Feminino , Lipopolissacarídeos , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Prednisolona/administração & dosagem , Prednisolona/química , Prednisolona/uso terapêutico , Ratos , Ratos Wistar , Óleo de Soja/química , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Viscosidade
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