Gemfibrozil Alleviates Cognitive Impairment by Inhibiting Ferroptosis of Astrocytes via Restoring the Iron Metabolism and Promoting Antioxidant Capacity in Type 2 Diabetes.

Diabetes-associated cognitive dysfunction (DACD) is considered a significant complication of diabetes and manifests as cognitive impairment. Astrocytes are vital to the brain energy metabolism and cerebral antioxidant status. Ferroptosis has been implicated in cognitive impairment, but it is unclear whether the ferroptosis of astrocytes is involved in the progression of DACD. PPARA/PPARα (peroxisome proliferator-activated receptor alpha) is a transcription factor that regulates glucose and lipid metabolism in the brain. In this study, we demonstrated that high glucose promoted ferroptosis of astrocytes by disrupting iron metabolism and suppressing the xCT/GPX4-regulated pathway in diabetic mice and astrocytes cultured in high glucose. Administration of gemfibrozil, a known PPARα agonist, inhibited ferroptosis and improved memory impairment in db/db mice. Gemfibrozil also prevented the accumulation of lipid peroxidation products and lethal reactive oxygen species induced by iron deposition in astrocytes and substantially reduced neuronal and synaptic loss. Our findings demonstrated that ferroptosis of astrocytes is a novel mechanism in the development of DACD. Additionally, our study revealed the therapeutic effect of gemfibrozil in preventing and treating DACD by inhibiting ferroptosis.

Effect of gemfibrozil on cardiotoxicity induced by doxorubicin in male experimental rats.

Cardiotoxicity is an adverse effect of the anticancer drug doxorubicin (DOX). Gemfibrozil (GEM) is a lipid-lowering drug with a number of biological properties such as anti-inflammatory and antioxidant activities. Therefore, we decided to investigate the effect of GEM on DOX-induced cardiotoxicity in rats. Twenty-eight adult male Wistar rats were divided into four experimental groups as follows: Group I received normal saline (2 ml/kg) orally for 14 days, group II received DOX (2.5 mg/kg; in six injections; accumulative dose: 15 mg/kg) intraperitonially for 14 days, group III received DOX + GEM (100 mg/kg) orally for 14 days concomitantly with DOX administration, and group IV received GEM orally for 14 days. Lipid panel, various biochemical biomarkers, and histological observations were evaluated in serum and heart samples. According to our results, DOX significantly increased the levels of lipid panel (triglycerides, total cholesterol, and low-density lipoproteins cholesterol) as well as markers of cardiac dysfunction (Aspartate aminotransferase, Creatine kinase-muscle/brain, Lactate dehydrogenase and Cardiac Troponin I). Moreover, DOX significantly increased malondialdehyde and nitric oxide levels in cardiac tissue. Furthermore, administration of DOX reduced the level of glutathione as well as the superoxide dismutase, catalase, and Glutathione peroxidase activities. DOX-treated rats showed significantly higher tumor necrosis factor-α and interleukin-1ß. GEM administration significantly attenuated the lipid panel and biochemical biomarkers in DOX-treated rats. Our results were confirmed by histopathological evaluations of the heart. Based on our findings, GEM is a promising cardioprotective agent in patients treated with DOX through mitigative effects on biochemical markers and oxidative stress indices.

Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1.

BACKGROUND/AIM: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers. METHODS: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin. Creatinine and urea were measured and animals were sacrificed and kidney was taken for histopathology. The following tissue markers were measured, heme oxygenase-1 (HO-1) activity, reduced glutathione, quantitative (real-time polymerase chain reaction) RT-PCR for gene expression of tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (ENOS) level. RESULTS: GII developed AKI demonstrated by significantly high urea and creatinine and severe diffuse (80-90%) tubular necrosis. TNF-α was highly and significantly elevated while the rest of tissue markers were significantly reduced in GI1 compared to other groups. GIV showed better results compared to GIII. There was a significant positive correlation between creatinine and TNF-α when combining GI and GII while there were significant negative correlation between creatinine and other tissue markers in same groups. Linear regression analysis demonstrated that HO-1 was the independent predictor of AKI demonstrated by elevated creatinine among GI and GII. CONCLUSIONS: Combination of sildenafil and gemfibrozil can be used in treatment of cisplatin-induced nephrotoxicity. HO-1 is a promising target for prevention and/or treatment of cisplatin-induced nephrotoxicity.

Gemfibrozil in Combination with Statins-Is It Really Contraindicated?

Gemfibrozil is a lipid-modifying agent that belongs to the fibric acid derivative class. Fibric acid derivatives activate peroxisome proliferator activated receptor α (PPAR-α). The primary role of these agents in clinical practice is for the management of hypertriglyceridemia. Triglycerides may be reduced by as much as 74 % in some patients. In addition to lowering triglycerides, these agents can also decrease very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as raise high-density lipoprotein cholesterol (HDL-C). Based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the National Lipid Association, pharmacologic therapy to reduce triglycerides should be considered when triglyceride levels are ≥500 mg/dL. While the use of gemfibrozil has decreased over the years for a variety of reasons, muscle-associated adverse effects is the predominant reason and the one that is most clinically relevant. However, despite these concerns, there are situations in which the use of gemfibrozil in combination with a statin may be necessary. Understanding the metabolism of gemfibrozil and the degree of interaction with the various statins will assist health-care providers to optimize safety when this combination is clinically indicated.

First and only symptom of undiagnosed diabetes mellitus: eruptive xanthoma.

Eruptive xanthoma (EX) is a very rare dermatosis mostly occurring due to high levels of serum triglycerides or uncontrolled diabetes mellitus. When EX is encountered, it is important to keep in mind that it could be a sign of severe underlying metabolic derangements. Early recognition can help avoid serious complications such as pancreatitis. After treatment of the underlying metabolic disorders, lesions mostly disappear without leaving scars. We present a case of a 55-year-old woman who presented with solely EX lesions and who was eventually diagnosed with diabetes mellitus and severe hypertriglyceridaemia.

Fibrates and fish oil, but not corn oil, up-regulate the expression of the cholesteryl ester transfer protein (CETP) gene.

Cholesteryl ester transfer protein (CETP) is a plasma protein that reduces high density lipoprotein (HDL)-cholesterol (chol) levels and may increase atherosclerosis risk. n-3 and n-6 polyunsaturated fatty acids (PUFAs) are natural ligands, and fibrates are synthetic ligands for peroxisome proliferator activated receptor-alpha (PPARα), a transcription factor that modulates lipid metabolism. In this study, we investigated the effects of PUFA oils and fibrates on CETP expression. Hypertriglyceridemic CETP transgenic mice were treated with gemfibrozil, fenofibrate, bezafibrate or vehicle (control), and normolipidemic CETP transgenic mice were treated with fenofibrate or with fish oil (FO; n-3 PUFA rich), corn oil (CO, n-6 PUFA rich) or saline. Compared with the control treatment, only fenofibrate significantly diminished triglyceridemia (50%), whereas all fibrates decreased the HDL-chol level. Elevation of the CETP liver mRNA levels and plasma activity was observed in the fenofibrate (53%) and gemfibrozil (75%) groups. Compared with saline, FO reduced the plasma levels of nonesterified fatty acid (26%), total chol (15%) and HDL-chol (20%). Neither of the oil treatments affected the plasma triglyceride levels. Compared with saline, FO increased the plasma adiponectin level and reduced plasma leptin levels, whereas CO increased the leptin levels. FO, but not CO, significantly increased the plasma CETP mass (90%) and activity (23%) as well as increased the liver level of CETP mRNA (28%). In conclusion, fibrates and FO, but not CO, up-regulated CETP expression at both the mRNA and protein levels. We propose that these effects are mediated by the activation of PPARα, which acts on a putative PPAR response element in the CETP gene.

Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the screening, monitoring, and treatment of adults with stage 1 to 3 chronic kidney disease. METHODS: This guideline is based on a systematic evidence review evaluating the published literature on this topic from 1985 through November 2011 that was identified by using MEDLINE and the Cochrane Database of Systematic Reviews. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, chronic heart failure, composite vascular outcomes, composite renal outcomes, end-stage renal disease, quality of life, physical function, and activities of daily living. This guideline grades the evidence and recommendations by using ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends against screening for chronic kidney disease in asymptomatic adults without risk factors for chronic kidney disease. (Grade: weak recommendation, low-quality evidence) RECOMMENDATION 2: ACP recommends against testing for proteinuria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme inhibitor or an angiotensin II-receptor blocker. (Grade: weak recommendation, low-quality evidence) RECOMMENDATION 3: ACP recommends that clinicians select pharmacologic therapy that includes either an angiotensin-converting enzyme inhibitor (moderate-quality evidence) or an angiotensin II-receptor blocker (high-quality evidence) in patients with hypertension and stage 1 to 3 chronic kidney disease. (Grade: strong recommendation) RECOMMENDATION 4: ACP recommends that clinicians choose statin therapy to manage elevated low-density lipoprotein in patients with stage 1 to 3 chronic kidney disease. (Grade: strong recommendation, moderate-quality evidence).

Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care.

OBJECTIVE: The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. DESIGN: Retrospective observational cohort study. METHODS: The primary endpoint was absolute change in TG levels measured using the last TG value pretreatment and the first TG value posttreatment. A pre-post quasi-experimental design was used to estimate the change in TG because of initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4⁺ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. RESULTS: A total of 493 patients (mean age, 46 years; 95% male) were included (46 patients receiving gemfibrozil; 80, fenofibrate; 291, atorvastatin; and 76, fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG [ΔTG, -45 mg/dL; 95% confidence interval (CI): -80 to -11] in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG, -66; 95% CI: -120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG, -39; 95% CI: -86 to 9). CONCLUSIONS: In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering TG values. Fish oil may still represent an attractive alternative for patients with moderately elevated TGs, particularly among patients who may not want or tolerate fibrates.

Gemfibrozil pretreatment affecting antioxidant defense system and inflammatory, but not Nrf-2 signaling pathways resulted in female neuroprotection and male neurotoxicity in the rat models of global cerebral ischemia-reperfusion.

Two important pathophysiological mechanisms involved during cerebral ischemia are oxidative stress and inflammation. In pathological conditions such as brain ischemia the ability of free radicals production is greater than that of elimination by endogenous antioxidative systems, so brain is highly injured due to oxidation and neuroinflammation. Fibrates as peroxisome proliferator-activated receptor (PPAR)-α ligands, are reported to have antioxidant and anti-inflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia-reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid-related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-α, nuclear factor-κB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti-hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sex-dependent neuroprotective/neurodegenerative potential.

Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense.

Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, IL-1ß, a proinflammatory cytokine, is implicated in the pathogenesis of neurodegenerative diseases. Although IL-1ß binds to its high-affinity receptor, IL-1R, and upregulates proinflammatory signaling pathways, IL-1R antagonist (IL-1Ra) adheres to the same receptor and inhibits proinflammatory cell signaling. Therefore, upregulation of IL-1Ra is considered important in attenuating inflammation. The present study underlines a novel application of gemfibrozil (gem), a Food and Drug Administration-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gem alone induced an early and pronounced increase in the expression of IL-1Ra in primary mouse cortical neurons. Activation of type IA p110α PI3K and Akt by gem and abrogation of gem-induced upregulation of IL-1Ra by inhibitors of PI3K and Akt indicate a role of the PI3K-Akt pathway in the upregulation of IL-1Ra. Gem also induced the activation of CREB via the PI3K-Akt pathway, and small interfering RNA attenuation of CREB abolished the gem-mediated increase in IL-1Ra. Furthermore, gem was able to protect neurons from IL-1ß insult. However, small interfering RNA knockdown of neuronal IL-1Ra abrogated the protective effect of gem against IL-1ß, suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Taken together, these results highlight the importance of the PI3K-Akt-CREB pathway in mediating gem-induced upregulation of IL-1Ra in neurons and suggest gem as a possible therapeutic treatment for propagating neuronal self-defense in neuroinflammatory and neurodegenerative disorders.

Gemfibrozilo versus aceite de Sacha Inchi en la reducción de niveles de triglicéridos séricos en Rattus rattus var albinus / Gemfibrozil versus Sacha Inchi oil in reducing serum triglyceride levels in Rattus rattus var albinus

Objetivo: Comparar efectos hipotrigliceridemiantes entre gemfibrozilo y aceite de Sacha Inchi en Rattus rattus var albinus. Materiales y Método: Se utilizaron 36 especímenes, los cuales fueron divididos al azar en 2 grupos experimentales (GE1 y GE2) y un grupo control (GC). Fueron sometidos a etapa de acondicionamiento por 2 semanas, luego alimentación rica en grasa por 2 semanas; posteriormente se administró aceite de Sacha Inchi y gemfibrozilo a GE1 y GE2, respectivamente. Se midieron los niveles de triglicéridos séricos en etapa basal, post-alimentación rica en grasa y tratamiento a una y dos semanas. Resultados: Disminución de niveles de triglicéridos séricos en GE1, GE2 y GC a dos semanas de tratamiento, de 45,57 %; 44,83 % y 27,24 % respectivamente. Diferencia de medias para GE1 y GE2 a una y dos semanas de tratamiento en relación a medias de valores postalimentación rica en grasa, fue muy altamente significativa; y diferencia entre grupos experimentales y GC a dos semanas de tratamiento fue significativa, con homogeneidad entre GE1 y GE2 (p=0,600). Conclusión: El aceite de Sacha Inchi demostró efectos hipotrigliceridemiantes, con eficacia similar al gemfibrozilo, en Rattus rattus var albinus, a una y dos semanas de tratamiento.

Objective: To compare the triglyceride lowering effect of gemfibrozil against that of Sacha Inchi oil in Rattus rattus var albinus. Materials and Methods: Thirty-six animals were used. They were divided in two experimental groups (GE1 and GE2) and a control group (CG). The animals underwent a conditioning stage for two weeks, afterwards they were fed with fat-rich meals; and later, the animals from the two experimental groups received Sacha Inchi oil and gemfibrozil, respectively. Serum triglyceride levels were measured at the beginning of the trial, after receiving the fat-rich food and after one and two weeks receiving the test drugs. Results: Serum triglyceride levels had 45,57%, 44,83%, and 27,24% reductions in GE1, GE2 and CG groups, respectively, after two weeks receiving the test drugs. The mean difference of triglyceride values in GE1 and GE2 groups after one and two weeks receiving the test drugs was highly significant compared with values measured after receiving the fat-rich meals; and the difference between the experimental groups and the control group after two weeks using the test drugs was also significant, and the results obtained in the GE1 and GE2 groups were homogeneous (p= 0,600). Conclusion: Sacha Inchi oil showed a triglyceride lowering effect which was similar inefficacy to that of gemfibrozil in Rattus rattus var albinus, after one and two weeks using the test products.

Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome.

OBJECTIVE: The obese Zucker rat (OZR) model of the metabolic syndrome is partly characterized by moderate hypercholesterolemia, in addition to other contributing comorbidities. Previous results suggest that vascular dysfunction in OZR is associated with chronic reduction in vascular nitric-oxide (NO) bioavailability and chronic inflammation, both frequently associated with hypercholesterolemia. As such, we evaluated the impact of chronic cholesterol-reducing therapy on the development of impaired skeletal muscle arteriolar reactivity and microvessel density in OZR and its impact on chronic inflammation and NO bioavailability. MATERIALS AND METHODS: Beginning at seven weeks of age, male OZR were treated with gemfibrozil, probucol, atorvastatin, or simvastatin (in chow) for 10 weeks. Subsequently, plasma and vascular samples were collected for biochemical/molecular analyses, while arteriolar reactivity and microvessel network structure were assessed by using established methodologies after 3, 6, and 10 weeks of drug therapy. RESULTS: All interventions were equally effective at reducing total cholesterol, although only the statins also blunted the progressive reductions to vascular NO bioavailability, evidenced by greater maintenance of acetylcholine-induced dilator responses, an attenuation of adrenergic constrictor reactivity, and an improvement in agonist-induced NO production. Comparably, while minimal improvements to arteriolar wall mechanics were identified with any of the interventions, chronic statin treatment reduced the rate of microvessel rarefaction in OZR. Associated with these improvements was a striking statin-induced reduction in inflammation in OZR, such that numerous markers of inflammation were correlated with improved microvascular reactivity and density. However, using multivariate discriminant analyses, plasma RANTES (regulated on activation, normal T-cell expressed and secreted), interleukin-10, monocyte chemoattractant protein-1, and tumor necrosis factor alpha were determined to be the strongest contributors to differences between groups, although their relative importance varied with time. CONCLUSIONS: While the positive impact of chronic statin treatment on vascular outcomes in the metabolic syndrome are independent of changes to total cholesterol, and are more strongly associated with improvements to vascular NO bioavailability and attenuated inflammation, these results provide both a spatial and temporal framework for targeted investigation into mechanistic determinants of vasculopathy in the metabolic syndrome.

Hypertriglyceridaemia-induced acute pancreatitis due to patient non-compliance.

A 34-year-old woman presented with acute and progressive pain in the upper abdomen with worsening nausea, vomiting and diarrhoea. Her pain was described as severe, sharp and stabbing, with radiation to her chest and back. The patient's amylase and lipase levels were only mildly elevated. However, triglyceride levels (10,039 mg/dL) were markedly elevated upon presentation and no other causes of acute pancreatitis (e.g. obstruction, alcohol and medication) were identified. The patient was treated with opioids to control her pain and gemfibrozil was initiated to reduce her triglycerides. In addition, the patient received enoxaparin for deep vein thrombosis prevention and insulin for hyperglycaemia which also have been shown to decrease elevated triglycerides. The patient subsequently required antibiotic therapy with piperacillin-tazobactam after developing fever and an elevated white blood cell count. We review the role of adjunctive therapy with heparin and insulin in a patient with recurrent pancreatitis probably because of hypertriglyceridaemia and medication non-compliance.

Clomiphene citrate-induced severe hypertriglyceridemia.

OBJECTIVE: To report a case of severe hypertriglyceridemia associated with clomiphene citrate (CC) treatment. DESIGN: Case report. SETTING: A patient referred to an endocrinology clinic of a state hospital. PATIENT(S): A 29-year-old, overweight woman with a history of polycystic ovary syndrome who had been given clomiphene citrate (CC) for ovulation induction and presented with severe hypertriglyceridemia. She had a family history of type 2 diabetes and hyperlipidemia. INTERVENTION(S): Clomiphene citrate treatment was discontinued, and gemfibrozil treatment at a dose of 1,200 mg/d was started. MAIN OUTCOME MEASURE(S): Serum lipid levels. RESULT(S): With the discontinuation of CC treatment and start of a specific lipid-lowering agent, the patient's lipid profile improved. After 3 months, CC therapy was restarted, and again severe hypertriglyceridemia developed, which resolved with the previous treatment strategies. CONCLUSION(S): Clomiphene citrate should be used cautiously in women having risk factors for dyslipidemia, and, even in the presence of a normal lipid profile, lipid levels should be closely monitored when CC treatment is instituted.

Prevention and treatment of atherosclerosis: a practitioner's guide for 2008.

Atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found in 80% to 90% of adults >/=30 years old in the United States. Successful treatment minimizes lifetime chances of cardiovascular events, morbidity, and mortality. Risk factors for atherosclerosis should be monitored, beginning in childhood, even in asymptomatic patients. Modifiable factors (e.g., blood pressure, smoking, serum lipids) and nonmodifiable factors (e.g., age, family history) are important in the overall assessment. Clinicians and patients can partner to produce an individualized treatment plan by choosing from a variety of standard approaches. In some patients, improved dietary choices, increased exercise, and smoking cessation will reduce risk to an acceptable degree. To lower risk further, lipid-lowering pharmacotherapy and antihypertensive medication may be combined with these lifestyle improvements. For most of these patients, reducing low-density lipoprotein cholesterol is the most important lipid-lowering goal, and it is best achieved with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). Some patients may benefit from adjunctive therapies that have proven effects (e.g., niacin, fibrates, plant stanols/sterols, omega-3 fatty acids). Antihypertensive regimens may involve stepwise adjustments of multiple medications. Good clinical judgment and communication of expectations and goals are critical for effective management of atherosclerosis.

Familial dysbetalipoproteinemia: a potentially fatal disorder.

Familial dysbetalipoproteinemia is an inherited disorder in which both cholesterol and triglycerides are elevated in the plasma of the blood, which pre-disposes people to coronary artery disease and peripheral vascular disease. We report two young boys with multiple cutaneous xanthomas and grossly abnormal serum cholesterol and triglycerides. Two of the family members had died of cardiovascular accidents in young age and rest of the family members had deranged lipid profile. Patients were managed with lipid lowering drugs and fat restriction diet. All family members were counseled and advised regular exercise and follow-up.

Peroxisome proliferator-activated receptors--from active regulators of macrophage biology to pharmacological targets in the treatment of cardiovascular disease.

Altered macrophage functions contribute to the pathogenesis of many infectious, immunological and inflammatory disease processes. Pharmacological modulation of macrophage activities therefore represents an important strategy for the prevention and treatment of inflammation-related diseases, such as atherosclerosis. This review focuses on recent advances on the role of the peroxisome proliferator-activated receptor transcription factor family in the modulation of lipid homeostasis and the inflammatory response in macrophages and the potential participation of these actions in the modulation of metabolic and cardiovascular disease.

Gemfibrozil ingestions reported to Texas poison control centers, 2000-2005.

Review of the literature failed to identify any information on potentially adverse ingestions of the cholesterol-lowering drug gemfibrozil (GEM) reported to poison control centers. Data from Texas poison control centers were used to describe the pattern of isolated GEM ingestions reported during 2000-2005. A total of 118 cases were identified. The mean maximum dose ingested was 2407 mg (range 300-18,000 mg) or 3.3 tablets/capsules (range 1-30 tablets/capsules). The patient was male in 55% of the cases. The most common circumstances of the exposure were unintentional therapeutic error (49%), general unintentional (34%), and suspected attempted suicide (11%). The management site was on site (84%), already at/en route to a health care facility (10%), referred to a health care facility (5%), and other (2%). The ingestion considered potentially toxic in 3% of the cases and no deaths were reported. A specific adverse clinical effect was listed for 9% of the cases, being gastrointestinal (5%), neurological (3%), or cardiovascular (1%). A specific treatment was listed for 54% of the cases, most frequently decontamination by dilution (39%) or food (15%). Potentially adverse isolated GEM ingestions reported to poison control centers generally do not involve serious medical outcomes and are successfully managed at home with a favorable outcome.