Combination Of Atorvastatin Research Articles

Comparison of Atorvastatin Alone and its Combination with Ezetimibe among Mixed Hyperlipidemic Patients

Background: Lowering the lipid levels remains the basis of recent medical therapy for preventing cardiovascular events. Statin treatment to attain target low-density lipoprotein cholesterol (LDL-C) levels is still associated with residual risk. Objective: To compare the efficacy of Atorvastatin and Atorvastatin combined with Ezetimibe among mixed hyperlipidemic patients. Methodology: This was a prospective interventional study among the 58 diagnosed mixed hyperlipidemic patients in the outpatient department (OPD) of the Department of Cardiology at the Sylhet MAG Osmani Medical College Hospital during February to November, 2023. Patients were divided into two groups. Group I had a combination of Atorvastatin 10mg and Ezetimibe 10mg, whereas Group II took Tab. Atorvastatin 20mg once daily at night for 12 weeks. Results: After 12 weeks of treatment, a comparison of lipid profile changes between the combination therapy group and the Atorvastatin group revealed a significant reduction (p<0.05) in total cholesterol (35.7% vs. 30.1%), triglycerides (30.6% vs. 16%), and LDL-C (47.5% vs. 40.1%). In the combination therapy group, ALT levels increased by 4.6%, compared to a 3.8% increase with Atorvastatin treatment alone. Combination therapy led to a 2.07% elevation in CK levels, while the Atorvastatin treatment group showed a 1.9% increase in CK values. The differences in HDL-C, ALT, and CK levels between the two groups were not statistically significant (p>0.05). Conclusion: The study revealed that combination therapy of Atorvastatin with Ezetimibe is more effective in reducing LDL-C, TG, and total cholesterol in patients with mixed hyperlipidemia compared to Atorvastatin alone. Journal of Monno Medical College June, 2024; 10 (1):23-29

Indicators of functional state of liver, blood lipid spectrum in patients with steatotic liver disease associated with metabolic dysfunction: modern approaches to complex treatment. Review

Objective — to study the dynamics of indicators of the functional state of the liver, the lipid spectrum of the blood, to evaluate the cardiovascular risk according to SCORE‑2 (Systematic Coronary Risk Estimation 2) scale under the influence of complex pathogenetic treatment of the detected disorders in patients with steatotic liver disease associated with metabolic dysfunction (SLDMD) in combination with obesity. Materials and methods. 46 outpatients with a diagnosis SLDMD were examined: 29 (63.1%) men and 17 (36.9%) women aged 32—55 years. The patients were divided into two groups. The main group included 19 (41.3%) persons who received atorvastatin: 20 mg/day for 90 days. The comparison group consisted of 27 (58.7%) patients who were prescribed ursodeoxycholic acid preparations in combination with atorvastatin: 250 mg (15 mg/kg of body weight) for 90 days. The control group consisted of 12 healthy persons of the appropriate age. The anthropometric criterion of obesity was the Quetelet index. Phenotypic variant of obesity was determined by the ratio of waist circumference/hip circumference (WC/HC). Among the patients of the main group, there were 9 (47.4%) persons with I degree of obesity ((32.6±2.2) kg/m2), 6 (31.5%) persons with II degree ( 35.8±3.6 kg/m2), and 4 (21.1%) persons with III degree (40.0±2.1kg/m2), in the comparison group there were 17 (62.9%), 6 (22.3%) and 4 (14.8%) patients, respectively. All patients received a differentiated diet with the calculation of the energy value, the quota of protein (1.4—1.6 g), fat (1.2—1.4 g), carbohydrates (2—3 g) per 1 kg of ideal body weight and dosed physical activity. For assessing the indicators of the functional state of the disease we determined: the level of general bilirubin and its fractions (direct and indirect), activity of serum aminotransferases, alkaline phosphatase, total cholesterol content in the blood serum, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol, very‑low‑density lipoprotein cholesterol, triglycerides. Results. In the majority of patients with SLDMD, a statistically significant (p <0.05) increase in the level of direct bilirubin in the blood, the activity of hepatic transaminases, alkaline phosphatase, and changes in the lipid spectrum of the blood were detected. According to the body mass index (BMI) most of the examined patients had visceral obesity. After the course of the combined therapy positive dynamics was marked in biochemical indices of the blood (p <0.05): decrease of the direct bilirubin level, hepatic transaminases, blood phosphatase. The lipid spectrum of the blood was close to normal (p <0.05). The addition of ursodeoxycholic acid to statin therapy contributes to a statistically significant reduction in total cardiovascular risk according to the SCORE 2 scale compared with atorvastatin monotherapy. All patients were recommended to continue the course of treatment (combination of atorvastatin and ursodeoxycholic acid) for 2 to 3 months. Conclusions. The use of a combination of statin and ursodeoxycholic acid in the treatment of patients with SLDMD and obesity helps to normalise the functional state of the liver and blood lipid parameters, reduce the degree of overall cardiovascular risk, and achieve clinical and biochemical remission of the pathological process in the liver.

Investigating the Effects of Simultaneous Administration of Melatonin and Atorvastatin against High Glucose-Induced Oxidative Stress and Apoptosis in Cultured Chondrocytes.

Osteoarthritis (OA) is a prevalent joint disorder categorized into phenotypic subtypes, including those associated with age, traumatic events, and metabolic syndrome. In the aging population, type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) frequently coexist. This can result in higher rates of disability and a greater financial burden. This study aimed to investigate the protective effects of melatonin and atorvastatin together against oxidative stress and apoptosis induced by high glucose in C28I2 human chondrocytes. After being pretreated for 6 hours with melatonin (10 and 100 μM) and atorvastatin (0.01 and 0.1 μM), C28I2 cells were exposed to a high concentration of D-glucose (75 mM) for 72 hours. The impact of a high D-glucose concentration (75 mM), with or without melatonin and/or atorvastatin, on cell viability, intra-cellular ROS generation, lipid peroxidation level, antioxidant activities, and the expression of proteins, including Bax, Bcl-2, and caspase-3, was analyzed. Melatonin and atorvastatin combination effectively inhibited high glucose-induced cytotoxicity, ROS production, and MDA and mitochondrial membrane potential levels. The combination of melatonin and atorvastatin was more successful in reducing ROS production compared to each of the drugs alone. Melatonin, but not atorvastatin, reversed high glucose-induced alteration in the catalase activity. Furthermore, the combination of melatonin and atorvastatin significantly enhanced the ability of each medication to lower the expression of pro-apoptotic protein Bax. The combination of melatonin and atorvastatin exerted greater protective effects against hyperglycemia-induced toxicity in chondrocytes.

Evaluation of muscular apoptotic changes and myogenin gene expression in experimental trichinosis after stem cells and atorvastatin added to ivermectin treatment

Trichinosis is a common parasitic disease that affects the striated skeletal muscles, causing apoptotic and degenerative changes associated with myogenin expression in the affected myocytes. Hence, this study aimed to assess the ameliorative effects of stem cells and atorvastatin added to ivermectin on the infected myocytes during the muscular phase of murine trichinosis. 120 laboratory Swiss albino male mice were divided into 10 groups, and each group was subdivided into intestinal and muscular phases (each n = 6); uninfected control; untreated infected control; infected received ivermectin monotherapy; infected received atorvastatin monotherapy; infected received stem cells monotherapy; infected received ivermectin and atorvastatin dual therapy; infected received ivermectin and stem cells dual therapy; infected received atorvastatin and stem cells dual therapy; infected received ivermectin 0.2, atorvastatin 40, and stem cells triple therapy; and infected received ivermectin 0.1, atorvastatin 20, and stem cells triple therapy. Intestinal phase mice were sacrificed on the 5th day post-infection, while those of the muscular phase were sacrificed on the 35th day post-infection. Parasitological, histopathological, ultrastructural, histochemical, biochemical, and myogenin gene expression assessments were performed. The results revealed that mice that received ivermectin, atorvastatin, and stem cell triple therapies showed the maximum reduction in the adult worm and larvae burden, marked improvement in the underlying muscular degenerative changes (as was noticed by histopathological, ultrastructural, and histochemical Feulgen stain assessment), lower biochemical levels of serum NK-κB and tissue NO, and lower myogenin expression. Accordingly, the combination of stem cells, atorvastatin, and ivermectin affords a potential synergistic activity against trichinosis with considerable healing of the underlying degenerative sequel.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Polypill versus medication monotherapy in the prevention of cardiovascular diseases in Iran: An economic evaluation study.

Cardiovascular diseases (CVDs) are one of the major diseases in developing and developed countries and have high prevalence and mortality rates. Pharmacological interventions, especially the use of combination medications, can have preventive effects in patients with CVDs. Recently, in the PolyIran trial, a combination of atorvastatin, hydrochlorothiazide, aspirin, and valsartan or enalapril (Polypill) was shown to be effective in providing survival benefits as a primary prevention strategy. In the present study, we examine the cost-effectiveness of the use of polypill compared to its individual components (named as medication monotherapy) in the prevention of CVDs in Iran. This was an economic evaluation study conducted to compare the cost-utility of polypill with that of medication monotherapy for 10,000 hypothetical cohorts of people over 35 years of age using the Markov model and with a lifetime horizon. The study perspective was patient perspective and direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio were estimated. To deal with uncertaintysensitivity analyses were used. The results showed that polypill, with the lowest costs (871 USD) and highest QALYs (14.55), had the most cost-utility than medication monotherapy. Also, the results showed that the highest sensitivities were related to the utilities of angina and stroke states. At the 21,768 USD threshold, polypill had a 92% probability of being cost-effective versus other medications. Considering that polypill had the most cost-utility, it is suggested that health system policymakers pay special attention to polypill in designing clinical guidelines. Also, through covering this medication by health insurance organizations, it is possible to complete the country's medicine pharmacopeia in preventing CVDs.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Biomedicine and pharmacotherapeutic effectiveness of combinatorial atorvastatin and quercetin on diabetic nephropathy: An in vitro study

IntroductionDiabetic nephropathy is a type of kidney disorder that develops as a complication of multifactorial diabetes. Diabetic nephropathy is characterized by microangiopathy, resulting from glucose metabolism, oxidative stress, and changes in renal hemodynamics. This study strived to evaluate the in vitro cytoprotective activity of atorvastatin (ATR), and quercetin (QCT) alone and in combination against diabetic nephropathy. MethodsThe MTT assay was utilized to analyze the effects of the test compounds on NRK-52E rat kidney epithelial cells. The detection of apoptosis and ability to scavenge free radicals was assessed via acridine orange-ethidium bromide (AO-EB) dual fluorescence staining, and 2,2-diphenyl-1-picrylhydrazyfree assay (DPPH), respectively. The ability of anti-inflammatory effect of the test compounds and western blot analysis against TGF-β, TNF-α, and IL-6 further assessed to determine the combinatorial efficacy. ResultsAtorvastatin and quercetin treatment significantly lowered the expression of TGF-β, TNF-α, and IL-6 indicating the protective role in Streptozotocin-induced nephrotoxicity. The kidney cells treated with a combination of atorvastatin and quercetin showed green fluorescing nuclei in the AO-EB staining assay, indicating that the combination treatment restored cell viability. Quercetin, both alone and in combination with atorvastatin, demonstrated strong DPPH free radical scavenging activity and further encountered an anti-oxidant and anti-inflammatory effect on the combination of these drugs. ConclusionNevertheless, there is currently no existing literature that reports on the role of QCT as a combination renoprotective drug with statins in the context of diabetic nephropathy. Hence, these findings suggest that atorvastatin and quercetin may have clinical potential in treating diabetic nephropathy.

A novel mouse model of familial combined hyperlipidemia and atherosclerosis.

Within the context of residual cardiovascular risk in post-statin era, emerging evidence from epidemiologic and human genetic studies have demonstratedthattriglyceride (TG)-rich lipoproteinsand their remnants are causally related to cardiovascular risk. While,carriers of loss-of-function mutations of ApoC3 havelow TG levelsand are protected from cardiovascular disease (CVD). Of translational significance,siRNAs/antisense oligonucleotide (ASO) targeting ApoC3 is beneficial for patients with atheroscleroticCVD. Therefore, animal models of atherosclerosiswith bothhypercholesterolemia and hypertriglyceridemia are important for the discovery of novel therapeutic strategies targeting TG-lowering on top of traditional cholesterol-lowering.In this study, we constructed a novel mouse model of familial combined hyperlipidemia through inserting a human ApoC3 transgene(hApoC3-Tg) into C57BL/6 J mice and injecting a gain-of-function variant of adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-D377Y concurrently with high cholesterol diet (HCD) feeding for 16 weeks. In the last 10 weeks, hApoC3-Tg mice were orally treated with a combination of atorvastatin (10 mg·kg-1·d-1) and fenofibrate (100 mg·kg-1·d-1). HCD-treated hApoC3-Tg mice demonstrated elevated levels of serum TG, total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Oral administration of atorvastatin and fenofibrate significantly decreased the plaque sizes of en face aorta, aortic sinus and innominate artery accompanied by improved lipid profileand distribution. In summary,this novel mouse model is of considerable clinical relevance for evaluation of anti-atherosclerotic drugsby targeting both hypercholesterolemia and hypertriglyceridemia.

Cuban policosanol: a natural compound for ischemic stroke treatment

Stroke is among the leading causes of mortality and disability; therefore, it constitutes a relevant health problem. Cuban policosanol presents lipid-lowering, antiplatelet, antioxidant and vascular endothelium protective properties, all of which give it a comprehensive anti-atherosclerotic effect. This review is aimed to show, analyze and discuss the main preclinical and clinical evidence of the effects of Cuban policosanol on ischemic stroke. Preclinical studies evidenced the anti-ischemic effects of preventive and therapeutic oral treatment with Cuban policosanol in Mongolian gerbils with cerebral ischemia induced by unilateral and permanent ligation of a carotid artery, and in global cerebral ischemia induced by bilateral clamping and recirculation of both carotids; being similar or superior to other anti-ischemic agents. Also, combination therapy with aspirin produced greater anti-stroke efficacy compared with aspirin monotherapy, but being similar to policosanol plus atorvastatin combination. This anti-stroke effect was associated to a serum thromboxane A2 (TxA2) concentrations reduction and prostacyclin (PgI2) increase, leading to a favorable TxA2/PgI2 balance, and also to the malondialdehyde (MDA) and sulfhydryl groups (SHG, lipid peroxidation and protein oxidation markers, respectively) reduction. Cuban policosanol combined with aspirin (standard therapy) improved and benefited patients with prior ischemic stroke in terms of functional and neurological outcomes, in open-label studies and in randomized, double-blind, controlled studies. These beneficial effects on stroke patients were associated with antioxidant and antiplatelet effects of policosanol. Also, the combinations of Cuban policosanol plus aspirin and atorvastatin plus aspirin compared in a clinical study significantly and similarly improved the neurological recovery of patients with ischemic stroke. Cuban policosanol was safe and well tolerated, with no serious adverse events occurring during the trials. In conclusion, Cuban policosanol is a safe and effective natural drug for ischemic stroke treatment, which is supported by preclinical and clinical evidences.

Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease.

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is an increasingly significant global health burden for which there is currently no effective treatment. The present study aimed to explore the underlying mechanisms and investigate the effects of donafenib and atorvastatin in MASLD. The effects of donafenib and atorvastatin on the activity and lipid metabolism of HepG2 cells were analyzed invitro. A rat model of MASLD was established induced by a high‑fat diet invivo. H&E and Oil red O staining were used to observe the improvement in MASLD, western blotting analysis was used to detect the expression of proteins related to fat metabolism and immunofluorescence was used to detect reactive oxygen species (ROS) levels. Invitro, donafenib and atorvastatin inhibited lipid accumulation in HepG2 cells. Invivo, donafenib and atorvastatin activated the AMP‑activated protein kinase (AMPK) pathway, downregulated the expressions of proteins related to fatty acid synthesis (sterol regulatory element‑binding protein‑1, 3‑hydroxy‑3‑methylglutaryl‑CoA reductase and fatty acid synthase) and upregulated the expression of proteins related to fatty acid β‑oxidation (carnitine palmitoyl‑transferase 1C and acyl‑CoA oxidase). The levels of free fatty acids, cholesterol and triglycerides in the liver and serum decreased in all three treatment groups. Additionally, donafenib and atorvastatin reduced oxidative stress in the liver tissue and decreased ROS levels. Low‑dose donafenib combined with atorvastatin improved MASLD by regulating fatty acid metabolism and reducing oxidative stress through activation of the AMPK signaling pathway.

Exploring non-antimicrobial agents as antibiotic alternatives: an in vitrostudy

Background:Microorganisms cause periapical and pulpal disorders, making root canal treatment (RCT) essential. Due to complex canal anatomy, bacteria may persist despite cleaning. Intracanal medicaments, such as calcium hydroxide and chlorhexidine, help eliminate residual bacteria, reduce inflammation, and enhance treatment outcomes by improving disinfection and compatibility.Aim:To assess the antimicrobial effectiveness of Triple Antibiotic Paste (TAP), Modified TAP, Sertraline (SSRI), Atorvastatin and the combination of Atorvastatin and Sertraline against Enterococcus faecalis.Materials and methods:A total of 30 samples were made, with 6samples from each group: TAP, Sertraline, Atorvastatin, Modified TAP, and Sertraline + Atorvastatin. The antimicrobial efficacy of the medicaments was evaluated using an agar well diffusion test by measuring inhibition zones around the medicaments. Statistical analysis included one-way ANOVA, with significance set at p &lt; 0.05.Results:A significant difference (p=0.001) in the diameter of growth inhibition zones was observed. The maximum inhibitory zone was found in Group 5: Sertraline+Atorvastatin.Conclusion:The combination of sertraline and atorvastatin demonstrated superior antimicrobial efficacy compared to modified TAP, TAP, sertraline, and atorvastatin used alone.

ULTRASOUND DIAGNOSTICS OF THE LIVER AS AN EFFECTIVE METHOD OF CONTROLLING NON-ALCOHOLIC FATTY LIVER DISEASE THERAPY IN RHEUMATOID ARTHRITIS PATIENTS

Today, the method of ultrasound diagnostics is the most widespread method of internal organs and tissues visualization. In particular, the liver ultrasound is the safest and most informative method of diagnosing non-alcoholic fatty liver disease (NAFLD) and an effective method of monitoring the effectiveness of NAFLD treatment, namely its manifestation of liver steatosis. The aim of this paper was to investigate the changes in the state of the liver by ultrasound in rheumatoid arthritis (RA) patients with the use of additional combined therapy of atorvastatin and essential phospholipids. We were examined and treated 77 RA patients with NAFLD (64 women (83.1%) and 13 men (16.9%)), under the age of 55 years old. The patients were divided into 3 studied groups. The first group (n=25) received additional atorvastatin, the second group (n=26) – essential phospholipids, and the third group (n=26) – combination of atorvastatin and essential phospholipids for 6 months. Ultrasound assessment of steatosis was performed before treatment, after 3 and 6 months of treatment. In the III group, an improvement of the ultrasound images was observed already after 3 months of combined use of atorvastatin and essential phospholipids, which was not observed in the separate use of these medicines in the I and II groups. In 6 months of treatment with the studied medicines, positive dynamics of the liver parenchyma echogenicity was observed in all studied groups.

Evaluation of Drug Utilization and Dose Intensity Pattern in Dyslipidemic Patients with Type 2 Diabetes Mellitus

AbstractDyslipidemia can increase the risk of cardiovascular disease in individuals with metabolic diseases. Patients may have to take multiple medications simultaneously, leading to polypharmacy. A retrospective study was conducted to evaluate drug utilization and dose intensity patterns in dyslipidemic patients with type 2 diabetes mellitus over an 8-month period at a tertiary care hospital. The study included the case sheets of patients diagnosed with dyslipidemia and type 2 diabetes. The required data for the study were collected from the patient's case sheets from the Medical Records Department (from June 2015 to May 2020). The data were documented using MS Excel 2013 and analyzed descriptively using SPSS software version 20. Among the 384 study population, 53% were males and 47% were females, with an age group of 45 to 59 years. Metformin and glimepiride were the most commonly prescribed oral hypoglycemic agents, while glibenclamide was the least prescribed. Atorvastatin was the most prescribed hypolipidemic agent. The combination of atorvastatin and fenofibrate was the most preferred combination therapy. The most frequently prescribed hypoglycemic and hypolipidemic agents were metformin and atorvastatin, respectively. Dyslipidemic patients with diabetes mellitus require the administration of multiple medications. It is crucial to monitor medication adherence and medication-related problems among these populations.

EFFECT OF COMBINED THERAPY ON LIPID METABOLISM IN RHEUMATOID ARTHRITIS PATIENTS WITH AND NON-ALCOHOLIC FATTY LIVER DISEASE

The article presents and analyzes the effect of combined therapy of atorvastatin and essential phospholipids in patients with rheumatoid arthritis (RA) and lipid metabolism indicators in non-alcoholic fatty liver disease (NAFLD). We examined and treated 77 RA patients with NAFLD (64 women (83.1%) and 13 men (16.9%)), under the age of 55 years old. The patients were divided into 3 groups. Additionally to RA antirheumatic therapy, the first group (n=25) received atorvastatin, the second group (n=26) - essential phospholipids, and the third group (n=26) - a combination of atorvastatin and essential phospholipids for 6 months. Assessment of the state of lipid metabolism was carried out by studying the laboratory indices of a lipid profile. A hypolipidemic effect was revealed when using both atorvastatin and essential phospholipids in patients with RA NAFLD, which increases with their combined use. Whereas the levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol levels in the blood serum significantly decrease with a simultaneous increase in the content of high-density lipoproteins (HDL) cholesterol. We revealed pronounced hypolipidemic and hepatoprotective effects in RA patients with NAFLD due to combined use of atorvastatin and essential phospholipids.

Rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling in chronic subdural hematoma

Chronic subdural hematoma (CSDH) remains a neurosurgical condition and a healthy burden especially in elderly patients. This study focuses on the functions of rapamycin and its related molecular mechanisms in CSDH management. A rat model of CSDH was induced, which developed significant hematoma on day 5 after operation. The rats were treated with rapamycin or atorvastatin, a drug with known effect on hematoma alleviation, or treated with rapamycin and atorvastatin in combination. The atorvastatin or rapamycin treatment reduced the hematoma development, blood-brain barrier permeability, neurological dysfunction in CSDH rats, and the combination treatment showed more pronounced effects. Human brain microvascular endothelial cells hCMEC/D3 were stimulated by hematoma samples to mimic a CSDH condition in vitro. The drug treatments elevated the cell junction-related factors and reduced the pro-inflammatory cytokines both in rat hematoma tissues and in hCMEC/D3 cells. Rapamycin suppressed the mTOR and STAT3 signaling pathways. Overexpression of mTOR or the STAT3 agonist suppressed the alleviating effects of rapamycin on CSDH. In summary, this study demonstrates that rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling.

Fixed triple combination of amlodipine, perindopril and atorvastatin in the focus of cardiovascular effectiveness and safety

The review outlines modern concepts of the relevance of fixed-dose combination therapy comprising angiotensin-converting enzyme inhibitor and dihydropyridine calcium channel antagonist as an antihypertensive component with the HMG-CoA reductase inhibitor when treating hypertensive patients. We have identified the realms of its possible clinical use taking into consideration the comorbidity peculiarities. In addition, we provide main features of the current drugs’ clinical pharmacodynamics and outline their role in real clinical practice. Nevertheless the emphasis was placed on the modern single-pill combination of amlodipin, atorvastatin and perindopril. We concisely report the results data collected from the large, randomized, double-blind major clinical trials regarding the effectiveness of single pill combination of amlodipine, atorvastatin and perindopril , primary focusing on their cardioprotective features and overall safety profile.

The combination of atorvastatin with Proanthocyanidin enhances antioxidant and reactive oxidative stress on HepG2 hepatocellular Carcinoma Cells.

The combination of atorvastatin with Proanthocyanidin enhances antioxidant and reactive oxidative stress on HepG2 hepatocellular Carcinoma Cells.

Management of metabolic syndrome by nutraceuticals prepared from chitosan and ferulic acid with or without beta-sitosterol and their nanoforms

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.

Cholesterol-Lowering Drugs as Potential Antivirals: A Repurposing Approach against Flavivirus Infections.

Flaviviruses, including Dengue (DENV), Zika (ZIKV), and Yellow Fever (YFV) viruses, represent a significant global health burden. The development of effective antiviral therapies against these viruses is crucial to mitigate their impact. This study investigated the antiviral potential of the cholesterol-lowering drugs atorvastatin and ezetimibe in monotherapy and combination against DENV, ZIKV, and YFV. In vitro results demonstrated a dose-dependent reduction in the percentage of infected cells for both drugs. The combination of atorvastatin and ezetimibe showed a synergistic effect against DENV 2, an additive effect against DENV 4 and ZIKV, and an antagonistic effect against YFV. In AG129 mice infected with DENV 2, monotherapy with atorvastatin or ezetimibe significantly reduced clinical signs and increased survival. However, the combination of both drugs did not significantly affect survival. This study provides valuable insights into the potential of atorvastatin and ezetimibe as antiviral agents against flaviviruses and highlights the need for further investigations into their combined therapeutic effects.