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1.
J Drug Target ; 31(7): 725-744, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37459647

RESUMO

Alzheimer's is one of the most common neurodegenerative illnesses that affect brain cellular function. In this disease, the neurons in the brain are considered to be decaying steadily but consistently by the accumulation of amyloid mass, particularly the ß-amyloids, amyloid proteins, and Tau proteins. The most responsible amyloid-proteins are amyloid-40 and amyloid-42, which have a high probability of accumulating in excess over the brain cell, interfering with normal brain cell function and triggering brain cell death. The advancement of pharmaceutical sciences leads to the development of Nanotheranostics technology, which may be used to diagnose and treat Alzheimer's. They are the colloidal nanoparticles functionalised with the therapeutic moiety as well as a diagnostic moiety. This article discusses the prognosis of Alzheimer's, various nanotheranostics approaches (nanoparticles, quantum dots, aptamers, dendrimers, etc), and their recent advancement in managing Alzheimer's. Also, various in-vitro and in-vivo diagnostic methodologies were discussed with respect to nanotheranostics.


Describing the pathophysiology of Alzheimer's with respect to amyloid ß in the prognosis of the diseasePresenting the various nanotheranostics techniques for the detection and treatment of Alzheimer's diseaseNanoparticles, Aptamers, and Dendrimers used as diagnostic and treatment entitiesIn-vivo (MRI, OI) and In-vitro (STM, TRPS) diagnostic approaches for detecting Alzheimer's disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Nanomedicina Teranóstica , Proteínas tau , Encéfalo/metabolismo , Amiloide/metabolismo
2.
Curr Drug Res Rev ; 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36892028

RESUMO

Odevixibat is synthesized through chemical modification of Benzothiazepine's structure. It is a tiny chemical that inhibits the ileal bile acid transporter and is used to treat a variety of cholestatic illnesses, including progressive familial intrahepatic cholestasis (PFIC). For cholestatic pruritus and liver disease development, bile acid transporter inhibition is a unique treatment strategy. Odevixibat reduces enteric bile acid reuptake. Oral odevixibat was also studied in children with cholestatic liver disease. Odevixibat received its first approval in the European Union (EU) in July 2021 for the treatment of PFIC in patients aged 6 months, followed by approval in the USA in August 2021 for the treatment of pruritus in PFIC patients aged 3 months. Bile acids in the distal ileum can be reabsorbed by the ileal sodium/bile acid cotransporter, a transport glycoprotein. Odevixibat is a sodium/bile acid co-transporter reversible inhibitor. An average 3 mg once-daily dose of odevixibat for a week resulted in a 56% reduction in the area under the curve of bile acid. A daily dose of 1.5 mg resulted in a 43% decrease in the area under the curve for bile acid. Odevixibat is also being evaluated in many countries for the treatment of other cholestatic illnesses, including Alagille syndrome and biliary atresia. This article reviews the updated information on odevixibat with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, drug-drug interactions, pre-clinical studies, and clinical trials.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33115396

RESUMO

AIMS: To study the toxicological profile and anti-hyperlipidemic effects of Spondias mombin leaves methanolic extract in experimental rats. BACKGROUND: Preventing high levels of lipids or its recurrence is currently one of the key aims of clinical and experimental studies. OBJECTIVE: This study was carried out to investigate the toxicological profile and anti-hyperlipidemic effects of methanolic extract of leaves of Spondias mombin. METHODS: The acute toxicity study was carried out where the limited dose of 2000 mg/kg body weight was administered to five rats at 48 h intervals. The interpretation was prepared and recorded for 24 h. In the sub-acute toxicity study, rats were treated with 250, 500, and 1000 mg/kg doses of the extract every 24 h for 28 days. The hematological, biochemical, and histopathological tests of treated animals were carried out at the end of the test. The anti-hyperlipidemic activity of plant extract (100, 200 mg/kg) was studied on Triton-X-100 induced hyperlipidemia in rats. Histopathological changes in the liver of rats were examined. RESULTS: For acute and subacute treatment, the extract did not reveal any signs of toxicity or mortality, or any significant effects on hematological, biochemical parameters, and histopathology of organs. The extract demonstrated an important anti-hyperlipidemic result by decreasing the serum levels of cholesterol, TGs, LDL, VLDL, and enhancing HDL. CONCLUSION: Taking up the evidence of the experimental study, we can conclude that the methanolic extract of Spondias mombin leaves helps in declining hyperlipidemia in rats and it can be safely used for a period of 28 days to treat hyperlipidemia.


Assuntos
Anacardiaceae , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Anacardiaceae/química , Animais , Colesterol/sangue , Feminino , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Hipolipemiantes/toxicidade , Masculino , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Ratos , Triglicerídeos/sangue
4.
Sci Pharm ; 85(3)2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28825665

RESUMO

The objective of this study is to evaluate the acute and subacute toxicity of the ethanolic extract of Marsdenia tenacissima (MTE) leaves (family: Asclepiadaceae) in albino rats. The acute toxicity was performed where the limit dose of 5000 mg/kg body weight used. Observations were made and recorded for 24 h, and once daily further for a period of 14 days. The rats were weighed and various observations, like mortality, behavior, injury, or any signs of illness were conducted once daily during the period. For subacute study, four groups of 10 animals (female rats) received 10% Tween 20 in distilled water (control), and 250, 500, and 1000 mg/kg of freshly-prepared extracts, respectively, every 24 h orally for 28 days. At the end of each study, hematological analysis and biochemical parameters were evaluated. Histopathological examination of vital organs of the animals were taken for gross findings, compared to controls. There was no significant difference (p > 0.05) observed in the relative organs, body weights, hematological, biochemical parameters, and gross abnormalities, compared to the control. No mortality was recorded. Therefore, analysis of results may lead to the conclusion that the medium-term oral administration of the MTE leaves for 28 days does not cause toxicity.

5.
J Chemother ; 26(6): 321-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25004945

RESUMO

Pomalidomide (Pomalyst(®)) is a synthetic compound derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects and third drug in the class of immunomodulatory drugs. Pomalidomide is under global development with Celgene Corporation, was approved by the U.S. Food and Drug Administration on February 8, 2013 to treat patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including bortezomib and lenalidomide. In October 2009, it has found orphan designation for the treatment of relapsed and refractory MM by the EMA, and on August 2013, marketing authorization has issued in Europe by gaining a positive response. It inhibits myeloma cell growth and angiogenesis directly. Pomalidomide is the latest myeloma cell growth inhibitor to be approved in both USA and EU. The predominant side effects are thrombocytopenia, neuropathy, and deep vein thrombosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom's macroglobulinemia. This article reviews the available information on pomalidomide with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, pre-clinical studies, and clinical trials.


Assuntos
Fatores Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Animais , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Talidomida/efeitos adversos , Talidomida/farmacocinética , Talidomida/farmacologia , Talidomida/uso terapêutico
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