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Clinical, Cosmetic and Investigational... 2024Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare...
Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.
PubMed: 38707607
DOI: 10.2147/CCID.S445163 -
Free Radical Biology & Medicine Aug 2024Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity...
Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.
Topics: Animals; Atorvastatin; Extracellular Traps; Sepsis; Mice; Imipenem; NADPH Oxidase 2; Disease Models, Animal; Lung Injury; Male; MAP Kinase Signaling System; Neutrophils; Signal Transduction; Humans; Mice, Inbred C57BL; Drug Therapy, Combination
PubMed: 38704053
DOI: 10.1016/j.freeradbiomed.2024.05.006 -
Annals of Medicine and Surgery (2012) May 2024Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are...
BACKGROUND AND PURPOSE
Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are exploring other options. This study focused on the effects of (FP) extracts on NAFLD induced by a high-fat diet in rats.
EXPERIMENTAL APPROACH
Thirty-five 10-week-old male Wister-Albino rats were divided into seven groups: normal diet control, high fat diet control, high fat diet with oral normal saline gavage, high fat diet with oral Atorvastatin gavage, and three groups receiving high fat diet with FP extract in 200 mg/kg, 400 mg/kg, and 700 mg/kg.Blood samples of rats were used for the measurement of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP).1×1 cm Liver biopsies were taken, stained with Trichrome Stain (Masson) and Hematoxylin and eosin (H&E) stain for evaluation by a pathologist.
FINDINGS/RESULTS
Lab results showed that FP extract inhibits weight gain, has positive effects on triglyceride and alkaline phosphatase levels, and reduces hepatocyte ballooning and inflammation in rats.
CONCLUSION
FP extract may lower liver enzymes and have a positive impact on triglyceride, LDL, and HDL levels in rats with NAFLD.
PubMed: 38694306
DOI: 10.1097/MS9.0000000000001890 -
International Journal of Pharmaceutics:... Jun 2024Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug...
Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day with superior activity for lactoferrin-decorated formulation.
PubMed: 38689601
DOI: 10.1016/j.ijpx.2024.100249 -
Journal of the American Heart... May 2024Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by...
BACKGROUND
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.
METHODS AND RESULTS
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]).
CONCLUSIONS
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.
Topics: Humans; Amlodipine; Male; Hypercholesterolemia; Hypertension; Female; Middle Aged; Atorvastatin; Aged; Taiwan; Drug Combinations; Treatment Outcome; Antihypertensive Agents; Retrospective Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Calcium Channel Blockers; Blood Pressure; Heptanoic Acids; Pyrroles
PubMed: 38686894
DOI: 10.1161/JAHA.123.033780 -
European Heart Journal Open Mar 2024The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid,...
The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.
AIMS
The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD).
METHODS AND RESULTS
Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; = 0.042), equipotent drugs (HR = 1.14; = 0.031), and other therapies cohorts (HR = 1.17; = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented.
CONCLUSION
In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.
PubMed: 38686352
DOI: 10.1093/ehjopen/oeae027 -
Journal of Integrative Neuroscience Apr 2024There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents...
BACKGROUND
There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase () inhibitors, Proproteinconvertase subtilisin/kexin type 9 () inhibitors and Niemann-Pick C1-like protein 1 () inhibitors on traumatic subdural hematomas.
METHODS
We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study.
RESULTS
A causal relationship was found between inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = -0.7593341 (Odds Ratio (OR) = 0.4679779), = 0.008366947 < 0.05)). However, no causal relationship was found between inhibitors and inhibitors and traumatic subdural hematoma ( inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), = 0.1126327), inhibitors: Inverse variance weighted (β = -0.02118558 (OR = 0.9790373), = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results.
CONCLUSIONS
This two-sample MR study suggests a potential causal relationship between inhibition (atorvastatin) and traumatic subdural hemorrhage.
Topics: Humans; Mendelian Randomization Analysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hematoma, Subdural; PCSK9 Inhibitors; Membrane Transport Proteins; Membrane Proteins; Hypolipidemic Agents; Atorvastatin; Proprotein Convertase 9; Hydroxymethylglutaryl CoA Reductases
PubMed: 38682216
DOI: 10.31083/j.jin2304076 -
International Journal of Molecular... Apr 2024The solute carrier organic anion transporter family member 1B1 () encodes the organic anion-transporting polypeptide 1B1 (OATP1B1 protein) that transports statins to...
The solute carrier organic anion transporter family member 1B1 () encodes the organic anion-transporting polypeptide 1B1 (OATP1B1 protein) that transports statins to liver cells. Common genetic variants in , such as *5, cause altered systemic exposure to statins and therefore affect statin outcomes, with potential pharmacogenetic applications; yet, evidence is inconclusive. We studied common and rare variants in up to 64,000 patients from UK Biobank prescribed simvastatin or atorvastatin, combining whole-exome sequencing data with up to 25-year routine clinical records. We studied 51 predicted gain/loss-of-function variants affecting OATP1B1. Both *5 alone and the *15 haplotype increased LDL during treatment (beta*5 = 0.08 mmol/L, = 6 × 10; beta*15 = 0.03 mmol/L, = 3 × 10), as did the likelihood of discontinuing statin prescriptions (hazard ratio*5 = 1.12, = 0.04; HR*15 = 1.05, = 0.04). *15 and *20 increased the risk of General Practice (GP)-diagnosed muscle symptoms (HR*15 = 1.22, = 0.003; HR*20 = 1.25, = 0.01). We estimated that genotype-guided prescribing could potentially prevent 18% and 10% of GP-diagnosed muscle symptoms experienced by statin patients, with *15 and *20, respectively. The remaining common variants were not individually significant. Rare variants in increased LDL in statin users by up to 1.05 mmol/L, but replication is needed. We conclude that genotype-guided treatment could reduce GP-diagnosed muscle symptoms in statin patients; incorporating further variants into clinical prediction scores could improve LDL control and decrease adverse events, including discontinuation.
Topics: Humans; Liver-Specific Organic Anion Transporter 1; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Exome Sequencing; United Kingdom; Male; Female; Biological Specimen Banks; Middle Aged; Aged; Simvastatin; Treatment Outcome; Atorvastatin; Polymorphism, Single Nucleotide; UK Biobank
PubMed: 38674010
DOI: 10.3390/ijms25084426 -
Biomolecules Apr 2024Ethyl (S)-4-chloro-3-hydroxybutyrate ((S)-CHBE) is an important chiral intermediate in the synthesis of the cholesterol-lowering drug atorvastatin. Studying the use of...
Ethyl (S)-4-chloro-3-hydroxybutyrate ((S)-CHBE) is an important chiral intermediate in the synthesis of the cholesterol-lowering drug atorvastatin. Studying the use of SpyTag/SpyCatcher and SnoopTag/SnoopCatcher systems for the asymmetric reduction reaction and directed coupling coenzyme regeneration is practical for efficiently synthesizing (S)-CHBE. In this study, Spy and Snoop systems were used to construct a double-enzyme directed fixation system of carbonyl reductase (BsCR) and glucose dehydrogenase (BsGDH) for converting 4-chloroacetoacetate (COBE) to (S)-CHBE and achieving coenzyme regeneration. We discussed the enzymatic properties of the immobilized enzyme and the optimal catalytic conditions and reusability of the double-enzyme immobilization system. Compared to the free enzyme, the immobilized enzyme showed an improved optimal pH and temperature, maintaining higher relative activity across a wider range. The double-enzyme immobilization system was applied to catalyze the asymmetric reduction reaction of COBE, and the yield of (S)-CHBE reached 60.1% at 30 °C and pH 8.0. In addition, the double-enzyme immobilization system possessed better operational stability than the free enzyme, and maintained about 50% of the initial yield after six cycles. In summary, we show a simple and effective strategy for self-assembling SpyCatcher/SnoopCatcher and SpyTag/SnoopTag fusion proteins, which inspires building more cascade systems at the interface. It provides a new method for facilitating the rapid construction of in vitro immobilized multi-enzyme complexes from crude cell lysate.
Topics: Glucose 1-Dehydrogenase; Enzymes, Immobilized; Biocatalysis; Hydrogen-Ion Concentration; Hydroxybutyrates; Temperature; Catalysis; Alcohol Oxidoreductases; Carbonyl Reductase (NADPH)
PubMed: 38672520
DOI: 10.3390/biom14040504 -
Biomedicines Apr 2024The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb...
Atorvastatin Treatment Significantly Increased the Concentration of Bone Marrow-Derived Mononuclear Cells and Transcutaneous Oxygen Pressure and Lowered the Pain Scale after Bone Marrow Cells Treatment in Patients with "No-Option" Critical Limb Ischaemia.
BACKGROUND
The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment.
METHODS
In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation.
RESULTS
Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin.
CONCLUSIONS
CRP and TcPO were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant.
PubMed: 38672276
DOI: 10.3390/biomedicines12040922