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1.
Nat Commun ; 11(1): 4885, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985503

RESUMO

Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with PD brain protein extracts. In microfluidic devices CLR01 reduced alpha-synuclein aggregation in cell somas when axonal terminals were exposed to alpha-synuclein oligomers. We then tested CLR01 in vivo in a humanized alpha-synuclein overexpressing mouse model; mice treated at 12 months of age when motor defects are mild exhibited an improvement in motor defects and a decreased oligomeric alpha-synuclein burden. Finally, CLR01 reduced alpha-synuclein-associated pathology in mice injected with alpha-synuclein aggregates into the striatum or substantia nigra. Taken together, these results highlight CLR01 as a disease-modifying therapy for PD and support further clinical investigation.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Neurônios Dopaminérgicos/efeitos dos fármacos , Organofosfatos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Masculino , Camundongos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Agregados Proteicos/efeitos dos fármacos , alfa-Sinucleína/química , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
2.
PLoS Pathog ; 16(8): e1008836, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866212

RESUMO

Anthrax is a major zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis in arid nonsylvatic savannahs, and by B. cereus biovar anthracis (Bcbva) in sylvatic rainforests. Bcbva-caused anthrax has been implicated in as much as 38% of mortality in rainforest ecosystems, where insects can enhance the transmission of anthrax-causing bacteria. While anthrax is well-characterized in mammals, its transmission by insects points to an unidentified anthrax-resistance mechanism in its vectors. In mammals, a secreted anthrax toxin component, 83 kDa Protective Antigen (PA83), binds to cell-surface receptors and is cleaved by furin into an evolutionary-conserved PA20 and a pore-forming PA63 subunits. We show that PA20 increases the resistance of Drosophila flies and Culex mosquitoes to bacterial challenges, without directly affecting the bacterial growth. We further show that the PA83 loop known to be cleaved by furin to release PA20 from PA63 is, in part, responsible for the PA20-mediated protection. We found that PA20 binds directly to the Toll activating peptidoglycan-recognition protein-SA (PGRP-SA) and that the Toll/NF-κB pathway is necessary for the PA20-mediated protection of infected flies. This effect of PA20 on innate immunity may also exist in mammals: we show that PA20 binds to human PGRP-SA ortholog. Moreover, the constitutive activity of Imd/NF-κB pathway in MAPKK Dsor1 mutant flies is sufficient to confer the protection from bacterial infections in a manner that is independent of PA20 treatment. Lastly, Clostridium septicum alpha toxin protects flies from anthrax-causing bacteria, showing that other pathogens may help insects resist anthrax. The mechanism of anthrax resistance in insects has direct implications on insect-mediated anthrax transmission for wildlife management, and with potential for applications, such as reducing the sensitivity of pollinating insects to bacterial pathogens.


Assuntos
Vacinas contra Antraz/administração & dosagem , Antraz/tratamento farmacológico , Antígenos de Bactérias/administração & dosagem , Bacillus anthracis/efeitos dos fármacos , Toxinas Bacterianas/administração & dosagem , Drosophila melanogaster/crescimento & desenvolvimento , Mosquitos Vetores/microbiologia , Substâncias Protetoras/administração & dosagem , Animais , Antraz/microbiologia , Culex , Drosophila melanogaster/imunologia , Drosophila melanogaster/microbiologia , Feminino , Masculino
3.
Life Sci ; 260: 118344, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853651

RESUMO

Pregabalin (PGB) drug abuse is common among the youth. It substituted tramadol before its recent schedule as a controlled drug since April 2019. PGB is an antiepileptic drug acting on the central nervous system. It blocks calcium channels regulating the action of neurotransmitters and causing prolonged depolarization. The present study aimed to investigate the toxic effect of long term pregabalin abuse on the reproductive function and body weight in both male and female albino rats and to evaluate the ameliorative effect of wheat germ oil (WGO). Forty-eight rats were randomly divided into eight groups. The first four groups were males and they were treated as follows: control group (1.5 mL saline), WGO group (1.5 mL L/kg), PGB group (300 mg/kg), and protective group (PGB + WGO). All doses were administrated once per day for 60 days by gastric gavage. The second four groups were females. They were divided and treated the same as the male groups. Pregabalin caused significant weight loss, decreased serum triglyceride level, and increased leptin gene expression in all rats. PGB affected male rats reproduction by decreasing total testosterone serum level and inhibiting spermatogenesis. Reproductive toxicity in females was caused by decreasing pituitary steroids, increasing gonadal hormones, and increasing the number of atretic ovarian follicles. Mechanism of toxicity may be attributed to the PGB oxidative stress effect that induced apoptosis and caused diffuse gonadal atrophy. WGO showed a protective effect on PGB induced toxicity as all measured parameters were relatively improved.


Assuntos
Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Leptina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleos Vegetais/farmacologia , Pregabalina/toxicidade , Reprodução/efeitos dos fármacos , Animais , Caspase 3/genética , Feminino , Leptina/genética , Óleos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos
4.
Int J Nanomedicine ; 15: 5217-5226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801687

RESUMO

Aim: Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly associated with gastric irritation and gastric ulceration. Therefore, the aim of study was to develop a novel oral drug delivery system with minimum gastric effects and improved dissolution rate for aceclofenac (ACF), a model BCS class-II drug. Methods: Self-emulsifying drug delivery systems (SEDDS) were formulated to increase the solubility and ultimately the oral bioavailability of ACF. Oleic acid was used as an oil phase, Tween 80 (T80) and Kolliphor EL (KEL) were used as surfactants, whereas, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) were employed as co-surfactants. Optimized formulations (F1, F2, F3 and F4) were analyzed for droplet size, poly dispersity index (PDI), cell viability studies, in vitro dissolution in both simulated gastric fluid and simulated intestinal fluid, ex vivo permeation studies and thermodynamic stability. Results: The optimized formulations showed mean droplet sizes in the range of 111.3 ± 3.2 nm and 470.9 ± 12.52 nm, PDI from 244.6 nm to 389.4 ± 6.51 and zeta-potential from -33 ± 4.86 mV to -38.5 ± 5.15 mV. Cell viability studies support the safety profile of all formulations for oral administration. The in vitro dissolution studies and ex vivo permeation analysis revealed significantly improved drug release ranging from 95.68 ± 0.02% to 98.15 ± 0.71% when compared with control. The thermodynamic stability studies confirmed that all formulations remain active and stable for a longer period. Conclusion: In conclusion, development of oral SEDDS might be a promising tool to improve the dissolution of BCS class-II drugs along with significantly reduced exposure to gastric mucosa.


Assuntos
Diclofenaco/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Disponibilidade Biológica , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Diclofenaco/administração & dosagem , Diclofenaco/farmacocinética , Liberação Controlada de Fármacos , Emulsões/administração & dosagem , Excipientes/química , Humanos , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Polietilenoglicóis/química , Polissorbatos/química , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacocinética , Ratos Sprague-Dawley , Solubilidade , Tensoativos/química
5.
Khirurgiia (Mosk) ; (7): 76-81, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736467

RESUMO

OBJECTIVE: To evaluate symptom-modifying effects of a two-month parenteral therapy with chondroitin sulfate («Mucosat¼) in patients with knee and/or hip osteoarthritis (OA) in various combinations of adjuvant therapy. MATERIAL AND METHODS: There were 70 patients with primary and/or post-traumatic unilateral/bilateral knee and/or hip osteoarthritis (Kellgren-Lawrence grade I-II). Pain syndrome severity was assessed as ≥ 50 mm (100-mm VAS), total Leken's index - ≥ 5 points. The main group comprised 40 patients who received Mucosat for 60 days. NSAIDs were additionally prescribed in 9 (22.5%) of these patients. The control group included 30 patients with intra-articular injection of hyaluronic acid. All patients underwent clinical and functional examination (rating scales VAS, Leken's total index, WOMAC index, EQ-5D health questionnaire), laboratory diagnosis (IL-1, IL-6, TNF-α), X-ray examination, assessment of adverse events at 5 visits. RESULTS AND CONCLUSION: Administration of chondroitin sulfate is associated with reduced local pain syndrome and functional normalization of musculoskeletal system. Prolonged pain-free period with high safety profile due to reduced need for NSAIDs is an advantage of Mucosat therapy. Thus, this drug may be recommended for initial therapy. A combination of chondroitin sulfate with intra-articular injection of hyaluronic acid may be perspective for optimization of therapy and secondary prevention of exacerbations of OA. Further research is required.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Artralgia/tratamento farmacológico , Artralgia/etiologia , Sulfatos de Condroitina/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Substâncias Protetoras/administração & dosagem , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(28): e20934, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664090

RESUMO

This study aimed to investigate the myocardial protective effect of liquid sodium phosphocreatine cardiac arrest in extracorporeal circulation surgery treating infants with atrial septal defects.Eighty-four infants with atrial septal defects who required extracorporeal circulation surgery treatment at our hospital from January 2016 to June 2018 were divided into an observation group and a control group through a digitally randomized method, with 42 cases in each group. The control group adopted the conventional modified St Thomas II high potassium cold liquid crystal cardiac arrest, while the observation group adopted the liquid sodium phosphocreatine cardiac arrest.The myocardial enzyme indexes of the 2 groups 3, 6, 12, and 24 hours postoperatively were higher than before establishing the cardiopulmonary bypass and the enzyme indexes of the control group at the same time were higher than that of the observation group; adenosine triphosphate, adenosine diphosphate, and other energy levels and the postoperative recovery rate energy levels of the observation group were higher than those in the control group, the difference was statistically significant (P < .05).Liquid sodium phosphocreatine cardiac arrest used in extracorporeal circulation surgery treating infants with atrial septal defects can reduce myocardial ischemia-reperfusion injury, maintain energy supply during ischemia, strengthen the St Thomas II effect, and aid postoperative cardiac function recovery of high potassium cold liquid crystal cardiac arrest used in infants with atrial septal defects and treated with extracorporeal circulation surgery.


Assuntos
Ponte Cardiopulmonar/métodos , Cardiotônicos/farmacologia , Parada Cardíaca Induzida/métodos , Comunicação Interatrial/cirurgia , Fosfocreatina/farmacologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Cardiotônicos/administração & dosagem , Estudos de Casos e Controles , Pré-Escolar , Circulação Extracorpórea/métodos , Feminino , Parada Cardíaca/induzido quimicamente , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/tratamento farmacológico , Humanos , Lactente , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/química , Miocárdio/enzimologia , Preservação de Órgãos/métodos , Fosfocreatina/administração & dosagem , Período Pós-Operatório , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/farmacologia , Substâncias Protetoras/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos
8.
Nitric Oxide ; 103: 1-3, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590117

RESUMO

It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Óxido Nítrico/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Substâncias Protetoras/farmacologia , Administração por Inalação , Infecções por Coronavirus/tratamento farmacológico , Feminino , Humanos , Masculino , Óxido Nítrico/administração & dosagem , Substâncias Protetoras/administração & dosagem , Fumantes , Fumar
9.
Life Sci ; 256: 117990, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574665

RESUMO

AIM: Luteolin and lycopene are common natural products, widely existing in nature, and both of which were reported to have various biological functions including anti-inflammatory, anti-obesity and anti-NAFLD. In the present study, we aimed to evaluate the therapeutic efficacy of luteolin and lycopene in combination and its latent molecular mechanisms in vitro and in vivo models of NAFLD. MAIN METHODS: Sodium palmitate (PA)-induced steatotic HepG2 cells and primary hepatocytes, and high-fat diet-induced C57BL/6J obese mice were treated with luteolin, lycopene and their combination. Metabolic parameters were measured. KEY FINDINGS: We found that luteolin (20 µM) + lycopene (10 µM) was the best therapeutic combination in PA-induced HepG2 cells, and significantly improve cell viability and lipid accumulation in PA-induced HepG2 cells and primary hepatocytes. In addition, luteolin (20 mg/kg) + lycopene (20 mg/kg) could ameliorate increased body weight and hepatocyte steatosis; regulate serum triglycerides, serum total cholesterol, hepatic triglycerides and hepatic total cholesterol; decrease serum alanine transaminase and aspartate transaminase. Furthermore, in vivo and in vitro, luteolin, lycopene and their combination had no effect on Sirt1 expression, but all of them could upregulate the expression of NAMPT, which could increase the level of NAD+, the co-substrate of Sirt1, indirectly activating Sirt1/AMPK pathway, and then inhibited lipogenesis and increased ß-oxidation, defensing the "first hit"; they also inactivated nuclear factor-κB (NF-κB) and decreased the levels of IL-6, IL-1ß and TNF-α, defensing the "second hit". SIGNIFICANCE: Thus, luteolin and lycopene in combination can effectively ameliorate "two-hit" in NAFLD through activation of the Sirt1/AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Luteolina/administração & dosagem , Licopeno/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Sirtuína 1/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória
10.
Ulus Travma Acil Cerrahi Derg ; 26(4): 509-516, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32589239

RESUMO

BACKGROUND: The hypothesis of our study is that sugammadex has protective efficacy against ischemia-reperfusion (I/R) injury in rats. METHODS: Our study included 28 male Wistar Albino rats. The rats were assigned to four groups. The sham group had no procedure other than anesthesia administration. The control group received three hours of ischemia and 24 hours of reperfusion. The Sgdx4 group received 4 mg/kg, and the Sgdx16 group received 16 mg/kg sugammadex intravenously, and then, reperfusion was applied. Histopathological investigation, and serum creatine kinase (CK), lactate dehydrogenase (LDH), and serum and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) analyses were performed. RESULTS: When the sham group and the control group were compared, there were statistically significant differences histopathologically (p<0.01). There was no significant difference between the Sgdx4 group compared with the sham and control groups histopathologically (p>0.01). There was a significant difference between the Sgdx16 group and the sham group histopathologically (p<0.01). There were significant differences between the sham and control groups concerning CK and LDH levels (p<0.01). There was a significant difference in the levels of CK between the control group and Sgdx4 group and in the levels of CK and LDH between the control group and Sgdx16 group (p<0.01). CONCLUSION: In our study, we examined the histological and biochemical protective effects of 4 mg/kg sugammadex on unilateral lower extremity I/R injury in rats. The findings suggest that a 4 mg/kg dose of sugammadex was more effective than a 16 mg/kg dose.


Assuntos
Substâncias Protetoras , Traumatismo por Reperfusão , Sugammadex , Animais , Modelos Animais de Doenças , Extremidade Inferior/fisiopatologia , Masculino , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Sugammadex/administração & dosagem , Sugammadex/uso terapêutico
14.
Biomed Environ Sci ; 33(4): 238-247, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438961

RESUMO

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. Conclusion: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.


Assuntos
Aflatoxina B1/toxicidade , Biflavonoides/farmacologia , Catequina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Venenos/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Proantocianidinas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
15.
Poult Sci ; 99(4): 1921-1927, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241472

RESUMO

The present study aimed to evaluate the immunopotentiating effect of plant-derived soyasaponin and its immunogenicity in chickens challenged with Newcastle disease virus (NDV). Soyasaponin was extracted from soybean seeds and detected using the phytochemical tests, followed by quantification through the dry-weight method. One-day-old broiler chicks (n = 90) were divided into 3 groups, named as A, B, and C. Group A birds were orally administrated with soyasaponin (5 mg/kg), followed by immunization with inactivated ND vaccine intramuscularly (IM), whereas group B birds were vaccinated with inactivated ND vaccine alone. Group C birds were kept unvaccinated. A booster dose on day 21 was also administered IM to group A and B birds. At day 35, all 3 groups were challenged with NDV. To determine the immunogenicity potential of soyasaponin, antibody titer was measured using the hemagglutination inhibition test before and after the NDV challenge. Histochemical examination was performed to determine the pathological changes associated with NDV infection. Foam formation and hemolytic activity confirmed the presence of saponin in soya bean extract. Group A birds showed a higher antibody response compared with group B and C birds. The disease challenge study showed that soyasaponin-adjuvanted NDV vaccine provided complete protection to group A birds against ND. Moreover, no side effects of soyasaponin were observed on the growth performance of birds during the experiment. Therefore, we can conclude that soyasaponin is a potential immunogenic agent and therefore could be a promising candidate to launch a protective humoral response against ND in chickens.


Assuntos
Galinhas , Imunidade Humoral/efeitos dos fármacos , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Vacinas Virais/administração & dosagem , Administração Oral , Animais , Substâncias Protetoras/administração & dosagem , Saponinas/administração & dosagem , Soja/química , Vacinas de Produtos Inativados/administração & dosagem
16.
Mar Drugs ; 18(3)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120786

RESUMO

Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria, hypoalbuminemia, and edema. At present, identification of effective and less toxic therapeutic interventions for nephrotic syndrome remains to be an important issue. In this study, we isolated fucoidan from Saccharina japonica and prepared its depolymerized fragment by oxidant degradation. Fucoidan and its depolymerized fragment had similar chemical constituents. Their average molecular weights were 136 and 9.5 kDa respectively. The effect of fucoidan and its depolymerized fragment on adriamycin-induced nephrotic syndrome were investigated in a rat model. The results showed that adriamycin-treated rats had heavy proteinuria and increased blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), and total triglyceride (TG) levels. Oral administration of fucoidan or low-molecular-weight fucoidan for 30 days could significantly inhibit proteinuria and decrease the elevated BUN, SCr, TG, and TC level in a dose-dependent manner. At the same dose (100 mg/kg), low-molecular-weight fucoidan had higher renoprotective activity than fucoidan. Their protective effect on nephrotic syndrome was partly related to their antioxidant activity. The results suggested that both fucoidan and its depolymerized fragment had excellent protective effect on adriamycin-induced nephrotic syndrome, and might have potential for the treatment of nephrotic syndrome.


Assuntos
Síndrome Nefrótica/prevenção & controle , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Alga Marinha/química , Administração Oral , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Oceanos e Mares , Polissacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Ratos
17.
Medicine (Baltimore) ; 99(11): e19527, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176105

RESUMO

OBJECTIVE: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effect for reducing post-electroconvulsive therapy (post-ECT) cognitive side effects is unclear. We conducted a systematic review and meta-analysis to assess the effectiveness of cognitive enhancers in the prevention of cognitive side effects due to ECT. METHODS: We identified relevant studies by searching electronic databases (e.g., PubMed, EMBASE, Web of Science, Cochrane Library). Only studies published up to October 2019 comparing cognitive enhancer vs placebo for cognitive function after ECT were included. The primary outcome extracted from the studies was cognitive function score. RESULTS: Five studies with 202 patients were included in this study. The cognitive enhancer group (CEG) had a significantly higher cognitive function score. Moreover, sensitivity analysis showed that no individual study had a significant impact on the overall results. CONCLUSIONS: This meta-analysis revealed that cognitive enhancers might improve cognitive function and reduce ECT-induced cognitive side effects. Nevertheless, more high-quality randomized controlled trials (RCTs) with long-term follow-up are still needed to make the final conclusion.


Assuntos
Transtornos Cognitivos/prevenção & controle , Cognição , Transtorno Depressivo/terapia , Eletroconvulsoterapia/efeitos adversos , Nootrópicos/administração & dosagem , Humanos , Período Pré-Operatório , Substâncias Protetoras/administração & dosagem
18.
Res Vet Sci ; 130: 184-192, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32199177

RESUMO

Cyprinid herpesvirus 3 (CyHV-3) is the etiological agent of koi herpersvirus disease (KHVD), which causes serious economic losses in global common carp and ornamental koi carp production of larvae as well as adult type fish. To control KHVD, vaccines against CyHV-3 utilizing different immunization routes have been developed, among them, oral vaccination is the most desirable method to prevent fish diseases occurring at the early larval stage. Here, we developed an oral subunit vaccine through the Saccharomyces cerevisiae cell surface display of CyHV-3 envelope protein pORF65, then, the recombinant yeast fed to Artemia which served as bio-encapsulation vector by subsequently feeding the common carp (Cyprinus carpio var. Jian) larvae. The fluorescent observation showed that the Artemia and S. cerevisiae could deliver intact antigen to the hindgut of carp larvae suggesting the possibility of the vector for oral immunization. On this basis, after three immunizations at a week interval, the oral vaccine induced high level of specific anti-pORF65 antibody. Meanwhile, a significant difference of immune-related genes expression occurred including cxca, IL-1ß, IFN-a1, lysozyme, IgM and CD8α between vaccined group and blank control group. In addition, 30% of relative percent survival of carp larvae after immunization was obtained post the animal infection assay, offered an certain immune protection. Our results indicated that the oral pORF65 subunit vaccine bioencapsulated in Artemia induced the activation of immune response and high level of antibodies, which could be served as an oral vaccine candidate for the prevention of CyHV-3 infection.


Assuntos
Antígenos Virais/imunologia , Doenças dos Peixes/imunologia , Infecções por Herpesviridae/veterinária , Herpesviridae/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Vacinação/veterinária , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Artemia/química , Infecções por Herpesviridae/imunologia , Imunidade Inata/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Saccharomyces cerevisiae/química , Vacinas Sintéticas/administração & dosagem , Proteínas do Envelope Viral/imunologia
19.
J Surg Res ; 251: 152-158, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145558

RESUMO

BACKGROUND: Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats. MATERIALS AND METHODS: Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed. RESULTS: Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna. CONCLUSIONS: This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.


Assuntos
Mesna/administração & dosagem , Substâncias Protetoras/administração & dosagem , Aderências Teciduais/prevenção & controle , Abdome/patologia , Animais , Avaliação Pré-Clínica de Medicamentos , Ratos Wistar , Aderências Teciduais/patologia
20.
Arch Med Res ; 51(1): 82-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113058

RESUMO

BACKGROUND AND AIM: Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of L-carnitine supplementation on liver enzymes. METHODS: The following databases were searched up to December 2018: PubMed, Scopus, ISI Web of Science, and the Cochrane library. Only randomized controlled trials (RCTs) evaluating the effects of L-carnitine supplementation on liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were included. Pooled effect size measured using random effect model (Dersimonian-Liard). RESULTS: A total of 16 studies (including 1025 participants) were included in the present meta-analysis. Pooled analysis indicated that L-carnitine supplementation significantly decreased ALT (weighted mean difference (WMD): -10.729 IU/L, 95% CI: -13.787, -7.672, p <0.001; I2 = 95.9%), AST (WMD: -7.149 IU/L, 95% CI: -9.202, -5.096, p <0.001; I2 = 93.5%) and GGT (WMD: -7.395: IU/L, 95% CI: -9.171, -5.619, p <0.001; I2 = 80.1%). Subgroup analysis revealed that effect of L-carnitine supplementation on liver enzymes was not significant in normal weight and healthy subjects. Baseline BMI and health status were the potential source of heterogeneity. CONCLUSION: L-carnitine supplementation showed beneficial hepato-protective effects on circulating liver enzymes.


Assuntos
Carnitina/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Carnitina/administração & dosagem , Citoproteção/efeitos dos fármacos , Suplementos Nutricionais , Humanos , Fígado/metabolismo , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , gama-Glutamiltransferase/efeitos dos fármacos , gama-Glutamiltransferase/metabolismo
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