scholarly journals Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock

2018 ◽  
Vol 53 (3) ◽  
pp. 152-156
Author(s):  
Chelsey M. McPheeters ◽  
Jennifer A. Wiedmar ◽  
Christina M. Pinkston ◽  
Kyle A. Weant
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Control Group ◽  
Vasopressor Therapy ◽  
Statin Group ◽  
Improved Outcomes ◽  
Anti Inflammatory ◽  
Time Of Admission ◽  
Statin Use

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

Influence of Long-term Statin use in Type 2 Diabetic Patients on Thyroid Nodularity in Iodine-sufficient Area

2011 ◽  
Vol 119 (08) ◽  
pp. 497-501 ◽  
Author(s):  
M. Chon ◽  
J. Suk ◽  
K. Oh ◽  
K. Kim ◽  
Y. Kim ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Statin Group ◽  
And Control ◽  
Type 2 Diabetic ◽  
Statin Use

AbstractStatins have marked beneficial effects on lipid profile, but also have pleiotropic actions. A previous study in an iodine-deficient area suggested that statin use is associated with reduced thyroid volume and nodularity. We performed this study to investigate how long-term statin use in type 2 diabetic patients affects thyroid nodularity in iodine-sufficient area.We recruited euthyroid type 2 diabetic patients, receiving statin therapy continuously for at least 5 years (statin group) and, age and sex matched statin-naive type 2 diabetic patients (control group). Subjects with past history of cancer, thyroid disease or treatment with lithium or amiodarone; family history of thyroid cancer; palpable goiter or thyroid nodule, and/or positive thyroperoxidase antibody were excluded. The prevalence, number, and volume of thyroid nodules, size of thyroid were evaluated in all subjects by high resolution ultrasound.Prevalence of non-palpable thyroid nodules of statin group (n=70) and control group (n=98) were 51 and 53% , respectively. There was no difference of prevalence, number, and volume of non-palpable thyroid nodules and size of thyroid between statin and control group. But, the patients aged between 60 and 65 years from statin group showed lower prevalence of non-palpable thyroid nodules than the patients with same age interval from control group (4 out of 12 patients, 33% , statin group; 19 out of 27 patients, 70% , control group; P=0.04).Long-term statin use in elderly type 2 diabetic patients was associated with lesser prevalence of thyroid nodules in an iodine-sufficient area. Our data might support a possible antiproliferative effect of statins on thyroid in old type 2 diabetic patients. But, the effect was not as strong as that in an iodine-deficient area and further studies with enough numbers of subjects and revised design will be needed.

Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study

2021 ◽  
pp. bjophthalmol-2021-318789
Author(s):  
Yixiong Yuan ◽  
Wei Wang ◽  
Xianwen Shang ◽  
Ruilin Xiong ◽  
Jason Ha ◽  
...  
Keyword(s):  
Large Scale ◽  
Conditional Logistic Regression ◽  
Control Group ◽  
Case Group ◽  
Conditional Logistic Regression Model ◽  
The People ◽  
Increased Risk ◽  
Nested Case Control ◽  
Statin Use

SynopsisIn a cohort of middle-aged and elderly Australians, we found that long-term statin use was associated with a higher risk of glaucoma onset. As to subtypes of statins, the increased risk was only found in rosuvastatin users.PurposeTo investigate the relationship between statin use and glaucoma onset in a 10-year longitudinal study.MethodsThis nested case–control study was based on data from a large-scale cohort of Australians aged over 45 years old. Medication exposure was identified by claims records from the Pharmaceutical Benefits Scheme during the follow-up period (2009–2016). The onset of glaucoma was defined as the people with at least three claims of antiglaucoma medications. Controls matched by age, gender and cardiovascular diseases were selected from participants without prescription of antiglaucoma medications. A conditional logistic regression model was used to assess the association between statin use and glaucoma onset.ResultsThe proportion of statin users was higher in the case group (40.5%) than that in the control group (38.4%). After adjusting for baseline characteristics and longitudinal claims records, statin use was not associated with glaucoma onset (OR 1.04, 95% CI 0.97 to 1.11). However, an increased risk of glaucoma onset was observed in participants with a longer duration of statin use (>3 years vs <1 year: OR 1.12, 95% CI 1.04 to 1.21). With respect to specific types of statins, participants taking rosuvastatin were more likely to suffer from glaucoma (OR 1.11, 95%CI 1.01 to 1.22). The use of other statins was not significantly associated with glaucoma onset.ConclusionsLong-term statin use was found to be associated with a higher risk of glaucoma onset in this study. Regarding specific types of statins, the increased risk of glaucoma onset was only observed in users of rosuvastatin.

scholarly journals Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities

2019 ◽  
Vol 20 (19) ◽  
pp. 4895 ◽  
Author(s):  
Mihee Jang ◽  
Jieun Kim ◽  
Yujin Choi ◽  
JeongKyu Bang ◽  
Yangmee Kim
Keyword(s):  
Septic Shock ◽  
Antibacterial Activity ◽  
Bioactive Peptides ◽  
Liver Toxicity ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Peptide Antibiotic ◽  
Gram Negative ◽  
Innate Defense ◽  
Anti Inflammatory

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.

Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment

2019 ◽  
Vol 105 (4) ◽  
pp. e1695-e1704 ◽  
Author(s):  
Felix Morales-Palomo ◽  
Miguel Ramirez-Jimenez ◽  
Juan F Ortega ◽  
Alfonso Moreno-Cabañas ◽  
Ricardo Mora-Rodriguez
Keyword(s):  
Metabolic Syndrome ◽  
Exercise Training ◽  
Fat Oxidation ◽  
Time Effect ◽  
Whole Body ◽  
Atherogenic Dyslipidemia ◽  
Control Group ◽  
Training Adaptations ◽  
Statin Group ◽  
Statin Use

Abstract Background Statins reduce atherogenic dyslipidemia and cardiovascular disease (CVD) risk in metabolic syndrome (MetS) individuals. Exercise training could also contribute to reduce CVD by improving cardiorespiratory fitness and fat oxidation. However, statin use could interfere with training adaptations. Methods A total of 106 MetS individuals were divided into statin users (statin group, n = 46) and statin-naïve (control group, n = 60). Groups were matched by age, weight, and MetS components. Subjects completed 16 weeks of high intensity interval training (HIIT). Before and after HIIT, muscle biopsies were collected to assess mitochondrial content (citrate synthase [CS] activity) and the activity of the rate limiting β-oxidation enzyme (3-hydroxyacyl-CoA-dehydrogenase [HAD]). Fasting plasma glucose, insulin, TG, HDL-c, and LDL-c concentrations were measured. Exercise maximal fat oxidation (FOMAX) and oxygen uptake (VO2PEAK) were determined. Results Training improved MetS similarly in both groups (MetS z-score -0.26 ± 0.38 vs. -0.22 ± 0.31; P &lt; 0.001 for time and P = 0.60 for time x group). Before training, the statin group had reduced muscle HAD activity and whole body FOMAX compared to the control group. However, 16 weeks of HIIT increased HAD and FOMAX in both groups (P &lt; 0.03, time-effect). The statin group did not prevent the increases in CS with HIIT observed in the control group (38% vs 64%, respectively; P &lt; 0.001, time-effect). Conversely, with training VO2PEAK improved less in the statin than in the control group (12% vs. 19%, respectively; P = 0.013, time × group effect). Conclusion Chronic statin use in MetS does not interfere with exercise training improvements in MetS components, FOMAX, or mitochondrial muscle enzymes (ie, CS and HAD). However, the statin group attenuated the improvements in VO2PEAK with training. Clinical Trial Information ClinicalTrials.gov identifier no. NCT03019796, January 13, 2017.

scholarly journals Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines

2018 ◽  
Author(s):  
Hussein Al-Hakeim ◽  
Ahmed Jasim Twayej ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Clinical Efficacy ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Future Research ◽  
Control Group ◽  
Clinical Effects ◽  
Indoleamine 2,3 Dioxygenase ◽  
Anti Inflammatory ◽  
Normal Controls

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-&gamma;, interleukin (IL)-4 and transforming growth factor (TGF)-&beta;1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-&gamma;, TGF-&beta;1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-&beta;1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

scholarly journals Study on Anti-Inflammatory Activity of Niloticin by Targeting MD-2 Based on Computer-Aided Drug Design and Biolayer Interferometry

2021 ◽  
Vol 8 (10) ◽  
Author(s):  
Chen G ◽  
◽  
Liu Y ◽  
Zhang M ◽  
Xu Y ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Myeloid Differentiation ◽  
Control Group ◽  
Toll Like Receptor ◽  
Expression Levels ◽  
Biolayer Interferometry ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory ◽  
Cortex Phellodendri

Niloticin is an active compound from Cortex phellodendri, but its antiinflammatory activity has not yet been explored. The aim of the present study was to assess the drug potential of niloticin and to study the MD-2-targeting mechanism of its anti-inflammatory activity. Niloticin’s drug potential was analyzed using the Traditional Chinese Medicine Systems Pharmacology Database. Molecular docking and biolayer interferometry technology were used to explore the anti-inflammatory mechanism of niloticin by targeting myeloid differentiation protein 2 (MD-2), which mediates a series of Toll-Like Receptor (TLR) 4-dependent inflammatory responses. The cytokines involved in the LPSTLR4/ MD-2-NF-κB pathway were evaluated by ELISA, RT-PCR, and western blot. The results showed that niloticin has drug potential and could bind to MD- 2. Niloticin had no impact on cell viability. Niloticin could significantly decrease the levels of NO, IL-6, TNF-a, and IL-1β (P<0.01) induced by LPS. IL-1β, IL-6, iNOS, TNF-a, and COX-2 mRNA expression levels were decreased by niloticin (all P<0.01). Compared with the control group, TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all P<0.01). In conclusion, niloticin is a potential MD-2 antagonist. It might interact with MD-2 to play an anti-inflammatory role by suppressing the activation of the LPS-TLR4/MD-2-NF-κB signaling pathway.

scholarly journals Alteration of Cytokine Profiles in Uranium Miners Exposed to Long-Term Low Dose Ionizing Radiation

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Kun Li ◽  
YiShui Chen ◽  
XiaoLiang Li ◽  
ShuJie Lei ◽  
QingFeng Chen ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Control Group ◽  
Low Doses ◽  
Cytokine Profiles ◽  
Uranium Miners ◽  
Antibody Arrays ◽  
Experimental Group

Objective.The aim of the study is to estimate the immune function through cytokine profiles in sera of uranium mines.Methods.Antibody arrays were used to detect 50 cytokines in sera of uranium miners. Miners who had continuously worked underground for <5 years were treated as control group and those who worked for⩾5 years as experimental group.Results.Of 28 measurable cytokines, the release of IL-1α, IL-1RI, IL-15, IL-3, and IP-10 were significantly upregulated in the experimental group, and no cytokine was found significantly downregulated. Other proinflammatory cytokines such as IFN-γ, IL-10, IL-6, and TNFαlevels were slightly upregulated in the experimental group. With adjustment to age, BMI, and cigarette smoking, IL-1αand IL-3 levels increased significantly with underground time.Conclusion.Alteration of cytokine profiles in this study may indicate persistent inflammatory responses in uranium miners exposed to long-term low doses radiation.

Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria

2012 ◽  
Vol 302 (7) ◽  
pp. F895-F904 ◽  
Author(s):  
Pramod K. Agarwal ◽  
Jacob van den Born ◽  
Harry van Goor ◽  
Gerjan Navis ◽  
Rijk O. B. Gans ◽  
...  
Keyword(s):  
Rat Model ◽  
Structural Damage ◽  
Kidney Diseases ◽  
Blood Pressure Reduction ◽  
Renal Diseases ◽  
Control Group ◽  
Renal Inflammation ◽  
Anti Inflammatory ◽  
Oral Nicotine

Many proteinuric renal conditions are accompanied by renal inflammation. Nicotine is known to have anti-inflammatory properties and is used in oral form to help subjects quit smoking. A potential anti-inflammatory role of nicotine in proteinuric renal diseases has not been investigated to date. We therefore evaluated the effects of oral nicotine in a rat model of proteinuria-induced renal inflammation. We used a well-established model of adult (24 wk of age) male Munich-Wistar-Frömter rats. Animals were given three different physiological doses of nicotine in drinking water for 28 wk until 52 wk of age (long term). A group without nicotine served as a parallel control. At 52 wk of age, the control group had a 2.1 times reduction in creatinine clearance, 3.2 times increase in urinary protein excretion, an increased focal glomerulosclerosis (FGS) score, increased glomerular desmin deposition, decreased glomerular podocin, and a higher accumulation of macrophages and myofibroblasts compared with 24-wk-old animals. Oral treatment with nicotine dose dependently preserved renal function and halted proteinuria progression, which were independent of blood pressure reduction. It also reduced FGS, desmin deposition, podocin loss, and density of renal macrophages and myofibroblasts. Nicotine also reduced the level of gene expression of the renal inflammatory markers monocyte chemoattractant protein and vascular cell adhesion molecule-1. In conclusion, long-term oral nicotine preserved kidney function, reduced proteinuria, reduced renal inflammation, and protected progression of renal structural damage in a rat model of proteinuria. We further suggest evaluating nicotine as a potential additional therapeutic option for treating proteinuric kidney diseases.

Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock

2011 ◽  
Vol 22 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Eduardo Tamayo ◽  
Ana Fernández ◽  
Raquel Almansa ◽  
Elena Carrasco ◽  
María Heredia ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Anti Inflammatory

Statins and hemoperfusion improve 28-day survival in septic shock patients

Open Medicine ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. 475-480
Author(s):  
Tsukasa Nakamura ◽  
Eiichi Sato ◽  
Nobuharu Fujiwara ◽  
Yasuhiro Kawagoe ◽  
Sayaka Maeda ◽  
...  
Keyword(s):  
Septic Shock ◽  
Regression Analysis ◽  
Stepwise Regression ◽  
Hdl Cholesterol ◽  
Polymyxin B ◽  
Multiple Stepwise Regression Analysis ◽  
Time Of Admission ◽  
Complete History ◽  
Statin Use

AbstractUncontrolled inflammation and endotoxin play a central role in septic shock. Statins may possess anti-inflammatory properties, and removal of endotoxin by hemoperfusion with polymyxin B-immobilized fiber (PMX-F) could have favorable effects on sepsis. We examined retrospectively whether pre-existing statin and hemoperfusion with PMX-F at the time of admission were separately and independently associated with decreased overall 28-day mortality in septic shock patients. Consecutive 173 patients with septic shock (71.2±10.7 years old, 115 male and 58 female) were included in the present study. All patients underwent a complete history and physical examination, determination of blood chemistries. Multiple stepwise regression analysis revealed that albumin, creatinine (inversely), statin use, hemoperfusion with PMX-F and HDL-cholesterol were independently correlated to 28-day survival in septic shock patients (R2=0.464). Our present study suggests that pre-existing statin use and hemoperfusion with PMX-F may separately and independently contribute to blunt the process of septic shock.

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