RESUMO
Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.
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Intolerância à Glucose , Inibidores de Hidroximetilglutaril-CoA Redutases , Resistência à Insulina , Microbiota , Humanos , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon , Intolerância à Glucose/tratamento farmacológico , Ácidos e Sais Biliares , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.
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Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Atorvastatina/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of Taohong Siwu decoction (, TSD) on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking. METHODS: Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group: control group, model group, atorvastatin group (AT, 2.0 mg/kg), and TSD groups (20, 10, 5 g/kg) after 7 d of acclimation. The model of atherosclerosis was successfully established except the control group by high fat diet (HFD) and vitamin D2. Biochemical analyzers were used to detect the levels of triglyceride (TG), total cholestero (TC), low density lipoprotein-cholesterol (LDL-C) and high density lipid-cholesterol (HDL-C) in blood lipid. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were determined by enzyme-linked immunosorbent assay. Sudan IV staining and Hematoxylin and eosin staining (HE staining) were performed to observe the pathological changes in aortic tissue. Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins. The expression of target proteins was further detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analysis. RESULTS: The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma. Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa-B (NF-κB). The results of qRT-PCR and Western blot analysis showed that the mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group. CONCLUSIONS: TSD can ameliorate atherosclerosis in rats, and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/MyD88/NF-κB signal pathway.
Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , NF-kappa B , Ratos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Ratos Sprague-Dawley , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Atorvastatina/uso terapêutico , Simulação de Acoplamento Molecular , Transdução de Sinais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Fator de Necrose Tumoral alfa/metabolismo , Lipídeos , ColesterolRESUMO
OBJECTIVES: The high cardiovascular disease burden globally and in Australia necessitates attention on statin expenditure, the primary pharmacological intervention for cardiovascular disease risk factors. The Pharmaceutical Benefits Scheme (PBS) subsidies approved statins for Australians. Managing PBS government expenditure occurs through price control strategies of statutory price decreases upon first generic entry and price disclosure. This study investigates the impact price control measures had on statin price evolution and government expenditure between 2010 and 2022. METHODS: Prescription and pricing data were obtained from Services Australia Medicare Statistics, and price reduction strategies from the PBS. Summary statistics compared and described statin price, prescription, number of brands, market share, and government expenditure to atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin price control timelines. RESULTS: Statin prices exposed to price control measures decreased irrespective of dosage and correlated with reductions in government expenditure, with a comparison of 2010 and 2022 showing annual statin expenditure declined by AU$833.5 million (83.25%) whereas prescriptions reduced by 3.0 million (15.7%). Effects of price disclosure on atorvastatin and rosuvastatin market share suggest industry-prompted price reductions may arise from market share loss, whereas reasons external to pricing prompted rosuvastatin to gain market share. CONCLUSIONS: Limited publications on contemporary effects of statin price control measures exist. This investigation found these measures reduced government expenditure for statins by AU$949.1 million, with the price reduction correlating with price control measures. In addition to affirming price control mechanisms remain effective in contemporary times, this investigation provides data for key insights into the Australian statin industry.
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População Australasiana , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Idoso , Humanos , Atorvastatina/uso terapêutico , Austrália , Revelação , Custos de Medicamentos , Gastos em Saúde , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Programas Nacionais de Saúde , Rosuvastatina Cálcica/uso terapêuticoRESUMO
Background: A high dose of statin is used to obtain an intensive lipid-lowering in stroke patients, even in patients with normal lipid levels. There are limited data on effect of dosage of statins and functional outcome in stroke patients. Objectives: To compare serum cholesterol levels with severity of stroke measured by infarct volume. To compare functional outcome measured by mRS at day 90 with the dose of statin. Materials and Methods: This retrospective observational study was conducted in KMC Hospital Manipal, India between 2016 and 2018. Result: A total of 100 consecutive patients were included in the study, out of which 60 (60.0%) were males. Hyperlipidemia was present in 65 (65.0%) patients. On comparing the serum cholesterol levels with infarct volume using MRI, patients with low volume of ≤70 ml had higher mean serum total cholesterol concentration (223.83 mg/dl), whereas patients with high volume of >70 ml had low mean cholesterol level (218.70 mg/dl). The patients were divided into those who received low dose (≤20 mg) versus high dose (≥40 mg equivalent) of Atorvastatin. On comparing the mRS values at baseline and on day 90 with the dose of statins, patients who received a higher dosage had a statistically significant fall in mRS (p-0.045) at day 90. Conclusion: It was found that serum cholesterol levels were inversely related to the stroke severity. However, a higher the dose of statins resulted in better functional outcome and survival in post-stroke patients, possibly due to its neuroprotective effect.
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Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Atorvastatina/uso terapêutico , Colesterol , Infarto , Resultado do TratamentoRESUMO
Introduction: Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE). Objective: To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events. Material and methods: A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety. Results: In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses. Conclusions: The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.
Introducción: la atorvastatina ha sido usada en el manejo de la dislipidemia y se conoce poco sobre la eficacia y seguridad de la administración de atorvastatina en altas dosis para la prevención secundaria de eventos cardiovasculares mayores (MACE). Objetivo: evaluar el impacto de altas dosis de atorvastatina en la prevención secundaria de MACE y eventos adversos. Material y métodos: se realizó una revisión sistemática y un metaanálisis de las bases de datos Pubmed, Embase, Bireme y Cochrane Library Plus, con un alcance temporal de 1990 a julio de 2022. Se incluyeron seis ensayos clínicos aleatorios con un total de 29,333 pacientes que fueron tratados con dosis de 80 mg, 10 mg o placebo de Atorvastatina donde los resultados principales evaluados fueron los eventos cardiovasculares mayores (MACE), la mortalidad y la seguridad del tratamiento. Resultados: en el estudio comparativo entre el uso de Atorvastatina de 80 mg y otras terapias, se encontró un riesgo relativo (RR) de 0.8 (IC95%: 0.69-0.92), lo que representa una reducción del 20% en el riesgo (RRR) y un número necesario a tratar (NNT) de 30 a 55. En el análisis de los efectos adversos, se observó un RR de 2.37 (IC95%: 0.86-6.53) y un número necesario a dañar (NNH) de 14 a 19. El uso de atorvastatina de 80 mg se asocia con eventos adversos similares a dosis menores. Conclusiones: el uso de atorvastatina de 80 mg es efectivo en la prevención secundaria de evento cardiovascular mayor (MACE). El medicamento tiene eventos adversos que deben de tomarse en cuenta en la prevención secundaria.
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Doenças Cardiovasculares , Humanos , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/prevenção & controleRESUMO
Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.
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Diabetes Mellitus Experimental , Hiperlipidemias , Securidaca , Ratos , Animais , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Ratos Wistar , Dieta Hiperlipídica/efeitos adversos , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Atorvastatina/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Metanol/análise , Metanol/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Sementes , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/análise , Flores , ColesterolRESUMO
BACKGROUND: The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood. OBJECTIVE: This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models. METHODS: Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects. RESULTS: In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2nd hr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels. CONCLUSION: This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance.
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Epilepsia , Convulsões , Camundongos , Animais , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , Levetiracetam , Lacosamida , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêuticoRESUMO
Objective: To investigate the application of atorvastatin (AT) combined with ezetimibe (EZ) in elderly patients with hypertension (HY) combined with type 2 diabetes mellitus (T2DM) and the significance analysis of changes in serum bilirubin levels during treatment. Methods: One hundred and twelve elderly patients with HY combined with T2DM admitted to our hospital from September 2019 to March 2022 were selected and divided into a control group (AT) and a combined group (AT + EZ) according to the random number table method, with 56 cases in each group. It revealed that blood glucose, lipid function, inflammatory factors, and serum bilirubin [(total bilirubin, direct bilirubin (DBIL), indirect bilirubin (IBIL))] were also compared in both groups. The combined group was divided into high and low expression groups according to the mean total bilirubin value, and the incidence of adverse reactions was compared between the two groups. Results: Glucose, lipid function, and inflammatory factors were lower in the combined group than in the control group (P < .05). Total bilirubin, DBIL, and IBIL were higher in the combined group than in the control group (P < .05). The total incidence of adverse reactions in the high expression group was significantly lower than that in the low expression group (12.50% vs. 28.57%, P < .05). Conclusion: AT combined with EZ can effectively improve glucose, lipids, inflammation and upregulate serum bilirubin in patients with HY combined with T2DM.
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Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Idoso , Atorvastatina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/uso terapêutico , Bilirrubina , Hipertensão/tratamento farmacológico , GlucoseRESUMO
Dyslipidemia, steatohepatitis and insulin resistance are among the components of metabolic syndrome (MS). Nutraceuticals containing chitosan, beta-sitosterol and/or ferulic acid and their nanostructures could have a potential role for management of MS. The aim of the present study was to assess the efficacy of the aforementioned nutraceuticals in treatment of MS in rat and their interaction with atorvastatin, a hypolipidemic drug. The two nutraceuticals and their nanostructures were prepared and the nanostructures were assessed by transmission electron microscope and Fourier-Transform Infra-red Spectrometry. MS was induced in rats by feeding high fructose-high fat diet (HFFD). Different groups of rats fed HFFD and treated with the different nutraceuticals, atorvastatin and atorvastatin in combination with different nutraceuticals, control fed on balanced diet and control consumed HFFD without treatments were run. Plasma glucose, lipid profile, aminotransferases activity, total antioxidant capacity, malondialdehyde, urea, creatinine, insulin, high sensitivity C-reactive protein, and adiponectin were assessed along with calculation of insulin resistance. Liver fat and histopathology were investigated. All nutraceuticals in original and nanostructures showed beneficial effects in the treatment of MS, superiority was ascribed to nutraceuticals composed of chitosan and ferulic acid in both forms. A more promising treatment of MS belonged to atorvastatin administered with the different nutraceuticals.
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Quitosana , Resistência à Insulina , Síndrome Metabólica , Ratos , Animais , Quitosana/farmacologia , Quitosana/uso terapêutico , Atorvastatina/uso terapêutico , Suplementos Nutricionais , Dieta Hiperlipídica/efeitos adversos , FrutoseRESUMO
The research was conducted to analyze the clinical effects and corresponding molecular mechanisms of short-term treatment of acute coronary syndromes (ACS) by different doses of atorvastatin. In the research, a total of 90 ACS patients were included as the samples and divided into an experimental group (conventional treatment+60mg/per time/late atorvastatin), control group 1 (conventional treatment+25mg/per time/late atorvastatin), and control group 2 (25mg/per time/late atorvastatin) according to different doses of atorvastatin. After that, their blood fat and inflammatory factors before and after treatment were analyzed. Total cholesterol (TC) and high-density liptein cholesterol (HDL-C) levels of the experimental group were inferior to those of control groups 1 and 2 in the 5th and 7th days (P<0.05). After treatment, visfatin, matrix metalloproteinase-9 (MMP-9), and brain natriuretic peptide (BNP) of patients in the experimental group and control groups 1 and 2 were notably inferior to those in control groups 1 and 2 (P<0.05). Besides, interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP) of patients in the experimental group and control groups 1 and 2 were inferior to those in control groups 1 and 2 after treatment (P<0.05). Based on the above results, the short-term treatment by large-dose atorvastatin could reduce blood far and inflammatory factor levels of ACS patients more effectively than by conventional dose, and further inhibit inflammatory reactions and improve patient prognosis with safety and feasibility.
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Síndrome Coronariana Aguda , Humanos , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Metaloproteinase 9 da Matriz , Nicotinamida Fosforribosiltransferase , Proteína C-Reativa/metabolismo , Colesterol , Resultado do TratamentoRESUMO
BACKGROUND: Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. METHODS: An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. RESULTS: Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. CONCLUSIONS: Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Rinite Alérgica , Ratos , Animais , Camundongos , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , NF-kappa B/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Rinite Alérgica/patologia , Mucosa Nasal/patologia , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Prostaglandinas/metabolismo , Ovalbumina/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Citocinas/metabolismoRESUMO
Recently, starvation-inducing nutrient deprivation has been regarded as a promising strategy for tumor suppression. As a first-line lipid-lowering drug, atorvastatin (ATV) significantly reduces caloric intake, suggesting its potential in starvation therapy for suppressing tumors. Accordingly, we developed a novel starvation therapy agent (HA-Se-ATV) in this study to suppress tumor growth by using hyaluronic acid (HA)-conjugated chitosan polymer-coated nano-selenium (Se) for loading ATV. HA-Se-ATV targets cancer cells, following which it effectively accumulates in the tumor tissue. The HA-Se-ATV nanoplatform was then activated by inducing a weakly acidic tumor microenvironment and subsequently releasing ATV. ATV and Se synergistically downregulate the levels of cellular adenosine triphosphate while inhibiting the expression of thioredoxin reductase 1. Consequently, the starvation-stress reaction of cancer cells is significantly elevated, leading to cancer cell death. Furthermore, the in vivo results indicate that HA-Se-ATV effectively suppresses tumor growth with a low level of toxicity, demonstrating its great potential for clinical translation.
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Neoplasias , Selênio , Humanos , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Selênio/farmacologia , Neoplasias/tratamento farmacológico , Concentração de Íons de Hidrogênio , Microambiente TumoralRESUMO
The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.
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Hematoma Subdural Crônico , Humanos , Atorvastatina/uso terapêutico , Atorvastatina/efeitos adversos , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Hematoma Subdural Crônico/cirurgia , Estudos Retrospectivos , Drenagem Linfática Manual , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy. AIM: The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members. METHODS: We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects. RESULTS: In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe. CONCLUSION: The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.
Assuntos
Doenças Cardiovasculares , Dislipidemias , Infecções por HIV , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Metabólica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Atorvastatina/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Pravastatina/uso terapêutico , LDL-Colesterol/uso terapêutico , Síndrome Metabólica/induzido quimicamente , HDL-Colesterol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sinvastatina/uso terapêutico , Dislipidemias/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Infecções por HIV/complicaçõesRESUMO
Cancer is one of the most challenging diseases to manage. A sizeable number of researches are done each year to find better diagnostic and therapeutic strategies. At the present time, a package of chemotherapy, targeted therapy, radiotherapy, and immunotherapy is available to cope with cancer cells. Regarding chemo-radiation therapy, low effectiveness and normal tissue toxicity are like barriers against optimal response. To remedy the situation, some agents have been proposed as adjuvants to improve tumor responses. Statins, the known substances for reducing lipid, have shown a considerable capability for cancer treatment. Among them, atorvastatin as a reductase (HMG-CoA) inhibitor might affect proliferation, migration, and survival of cancer cells. Since finding an appropriate adjutant is of great importance, numerous studies have been conducted to precisely unveil antitumor effects of atorvastatin and its associated pathways. In this review, we aim to comprehensively review the most highlighted studies which focus on the use of atorvastatin in cancer therapy.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias , Radioterapia (Especialidade) , Humanos , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunoterapia , Adjuvantes Imunológicos , Neoplasias/tratamento farmacológicoRESUMO
Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients' daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient's daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.
Assuntos
Anti-Helmínticos , Antimaláricos , Antineoplásicos , Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Metformina , Monofosfato de Adenosina/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Helmínticos/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antimaláricos/uso terapêutico , Antineoplásicos/uso terapêutico , Atorvastatina/uso terapêutico , Neoplasias da Mama/patologia , Colesterol , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Masculino , Mebendazol/uso terapêutico , Metformina/uso terapêutico , Ácido Mevalônico/uso terapêutico , Propranolol/uso terapêutico , Proteínas Quinases/metabolismo , Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf , Receptores Adrenérgicos beta 2/uso terapêutico , TirosinaRESUMO
BACKGROUND: Statins are first-line lipid-lowering agents with tolerable adverse reactions, low cost, and high availability worldwide. The potent anti-inflammatory, antioxidant, anti-thrombotic and immunomodulatory effects of statins propose them as an option against COVID-19 infection. OBJECTIVE: In this randomized triple-blind placebo-controlled clinical trial, we have investigated the atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19 patients. METHODS: In this study, 52 mild to moderate hospitalized COVID-19 patients who fulfilled the inclusion criteria were allocated to the treatment group to receive 40 mg atorvastatin orally once daily for two weeks (n=26) or the placebo group (n=26). Patients' symptoms and laboratory investigations were assessed at baseline and during the follow-up period. We also evaluated the duration of hospitalization and supplemental oxygen therapy as endpoints. RESULTS: After 14-day of follow-up, the oxygen saturation (SaO2) was significantly higher, and the serum high sensitivity C-reactive protein (hs-CRP) level was lower in the treatment group compared to the placebo group. Moreover, at the end of the followup in the treatment group, the lymphocyte count was higher, and the duration of symptom resolution was shorter but not significant. Additionally, in the treatment group, the length of supplemental oxygen therapy and hospitalization duration were meaningfully shorter. Our results revealed that the mortality rate was almost twice higher in the placebo group compared to the treatment group, without any significant adverse drug reaction. CONCLUSION: Atorvastatin significantly reduces supplemental oxygen need, hospitalization duration, and serum hs-CRP level in mild to moderate hospitalized COVID-19 patients.
Assuntos
COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Proteína C-Reativa/metabolismo , Projetos Piloto , Método Duplo-Cego , OxigênioRESUMO
BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).
Assuntos
Tratamento Farmacológico da COVID-19 , Deterioração Clínica , Inibidores de Hidroximetilglutaril-CoA Redutases , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Interleucina-6 , SARS-CoV-2 , Resultado do TratamentoRESUMO
Objective: To analyze the significance of ezetimibe in combination with low- to moderate-intensity atorvastatin adjuvant aspirin therapy for cerebrovascular disease. Methods: 110 patients with cerebrovascular disease treated in our hospital from June 2020 to June 2021 were selected and divided into 55 patients in the control group and 55 patients in the study group according to the lottery method. After a comprehensive examination, patients in the two groups should be given aspirin for treatment; the control group was treated with conventional dose of atorvastatin on top of the above, and the study group was given ezetimibe and medium-low-dose atorvastatin on top of aspirin treatment, activities of daily living (ADL) score, carotid artery intima-media thickness, lipid level, coagulation level, clinical effect, and adverse rate of the two groups which were tested and compared. Results: After treatment, ADL score, high-density leptin cholesterol (HDL-C), and ATIII levels increased, while carotid artery media thickness, triglyceride (TG), total cholesterol (TC), low-density leptin cholesterol (LDL-C), DD, PC, and hs-CRP levels decreased (P < 0.05). After treatment, ADL score, HDL-C, and ATIII levels were higher in the study group. The levels of carotid media thickness, TG, TC, LDL-C, DD, PC, and hs-CRP were significantly lower (P < 0.05). The clinical effect of the study group was outstanding (P < 0.05). The defect rate of the study group was lower than that of the control group, but there was no difference (P < 0.05). Conclusion: Ezetimibe combined with medium- and low-intensity atorvastatin with aspirin in the treatment of cerebrovascular diseases can effectively improve the coagulation function of patients, reduce the level of inflammatory factors in patients, and improve the level of blood lipids in patients, with high safety and worthy of clinical application.