JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Two-Dimensional Bicapped Supramolecular Hybrid Semiconductor Material Constructed from the Insulators ?-Keggin Polyoxomolybdate and 4,4-Bipyridine.
Inorg Chem
PUBLISHED: 12-23-2013
Show Abstract
Hide Abstract
A new organic-inorganic hybrid material [SiMo14O44](H4,4-bpy)2·xH2O (4,4-bpy = 4,4-bipyridine) was synthesized using a hydrothermal method. The compound was characterized using single crystal X-ray diffraction (XRD), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-vis), and X-ray photoelectron spectroscopy (XPS). XRD studies on selected single crystals suggested that the compound consists of supramolecular 2D layer structures composed of capped ?-Keggin polyoxomolybdate anions and 4,4-bpy organic ligands. Absorption measurements show a band gap of 2.99 eV in the hybrid which suggests a semiconducting nature compared to the insulating free ?-Keggin and 4,4-bpy. The magnetic susceptibility of the hybrid material was investigated in the temperature range 1.8-300 K obeying the Curie-Weiss law above 70 K. Experimentally measured magnetic moment of 2.71 ?B/formula indicates possible mixed valent molybdenum in the compound. The XPS measurements confirm the presence of both Mo(V) and Mo(VI) in the ratio 15:85 resulting in the structural formula of the hybrid as [SiMo(V)2Mo(VI)12O44](H4,4-bpy)2·xH2O.
Related JoVE Video
Inflammatory responses induced by lipopolysaccharide are amplified in primary human monocytes but suppressed in macrophages by complement protein C5a.
J. Immunol.
PUBLISHED: 09-16-2013
Show Abstract
Hide Abstract
Monocytes and macrophages are important innate immune cells equipped with danger-sensing receptors, including complement and Toll-like receptors. Complement protein C5a, acting via C5aR, is shown in this study to differentially modulate LPS-induced inflammatory responses in primary human monocytes versus macrophages. Whereas C5a enhanced secretion of LPS-induced IL-6 and TNF from primary human monocytes, C5a inhibited these responses while increasing IL-10 secretion in donor-matched human monocyte-derived macrophages differentiated by GM-CSF or M-CSF. G?i/c-Raf/MEK/ERK signaling induced by C5a was amplified in macrophages but not in monocytes by LPS. Accordingly, the G?i inhibitor pertussis toxin and MEK inhibitor U0126 blocked C5a inhibition of LPS-induced IL-6 and TNF production from macrophages. This synergy was independent of IL-10, PI3K, p38, JNK, and the differentiating agent. Furthermore, C5a did not inhibit IL-6 production from macrophages induced by other TLR agonists that are selective for Toll/IL-1R domain-containing adapter inducing IFN-? (polyinosinic-polycytidylic acid) or MyD88 (imiquimod), demonstrating selectivity for C5a regulation of LPS responses. Finally, suppression of proinflammatory cytokines IL-6 and TNF in macrophages did not compromise antimicrobial activity; instead, C5a enhanced clearance of the Gram-negative bacterial pathogen Salmonella enterica serovar Typhimurium from macrophages. C5aR is thus a regulatory switch that modulates TLR4 signaling via the G?i/c-Raf/MEK/ERK signaling axis in human macrophages but not monocytes. The differential effects of C5a are consistent with amplifying monocyte proinflammatory responses to systemic danger signals, but attenuating macrophage cytokine responses (without compromising microbicidal activity), thereby restraining inflammatory responses to localized infections.
Related JoVE Video
Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism.
FASEB J.
PUBLISHED: 08-20-2013
Show Abstract
Hide Abstract
Excessive uptake of fatty acids and glucose by adipose tissue triggers adipocyte dysfunction and infiltration of immune cells. Altered metabolic homeostasis in adipose tissue promotes insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease. Inflammatory and metabolic processes are mediated by certain proteolytic enzymes that share a common cellular target, protease-activated receptor 2 (PAR2). This study showed that human and rat obesity correlated in vivo with increased expression of PAR2 in adipose tissue, primarily in stromal vascular cells (SVCs) including macrophages. PAR2 was expressed more than other PARs on human macrophages and was increased by dietary fatty acids (palmitic, stearic, and myristic). A novel PAR2 antagonist, GB88 (5-isoxazoyl-Cha-Ile-spiroindene-1,4-piperidine), given orally at 10 mg/kg/d (wk 8-16) reduced body weight by ?10% in obese rats fed a high-carbohydrate high-fat (HCHF) diet for 16 wk, and strongly attenuated adiposity, adipose tissue inflammation, infiltrated macrophages and mast cells, insulin resistance, and cardiac fibrosis and remodeling; while reversing liver and pancreatic dysfunction and normalizing secretion of PAR2-directed glucose-stimulated insulin secretion in MIN6 ? cells. In summary, PAR2 is a new biomarker for obesity, and its expression is stimulated by dietary fatty acids; PAR2 is a substantial contributor to inflammatory and metabolic dysfunction; and a PAR2 antagonist inhibits diet-induced obesity and inflammatory, metabolic, and cardiovascular dysfunction.-Lim, J. Iyer A., Liu L., Suen J. Y., Lohman R.-J., Seow V., Yau M.-K., Brown, L., Fairlie, D. P. Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism.
Related JoVE Video
Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.
J. Biol. Chem.
PUBLISHED: 07-12-2013
Show Abstract
Hide Abstract
Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1?-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1?, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1?-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.
Related JoVE Video
An mRNA atlas of G protein-coupled receptor expression during primary human monocyte/macrophage differentiation and lipopolysaccharide-mediated activation identifies targetable candidate regulators of inflammation.
Immunobiology
PUBLISHED: 04-10-2013
Show Abstract
Hide Abstract
G protein-coupled receptors (GPCRs) are among the most important targets in drug discovery. In this study, we used TaqMan Low Density Arrays to profile the full GPCR repertoire of primary human macrophages differentiated from monocytes using either colony stimulating factor-1 (CSF-1/M-CSF) (CSF-1 M?) or granulocyte macrophage colony stimulating factor (GM-CSF) (GM-CSF M?). The overall trend was a downregulation of GPCRs during monocyte to macrophage differentiation, but a core set of 10 genes (e.g. LGR4, MRGPRF and GPR143) encoding seven transmembrane proteins were upregulated, irrespective of the differentiating agent used. Several of these upregulated GPCRs have not previously been studied in the context of macrophage biology and/or inflammation. As expected, CSF-1 M? and GM-CSF M? exhibited differential inflammatory cytokine profiles in response to the Toll-like Receptor (TLR)4 agonist lipopolysaccharide (LPS). Moreover, 15 GPCRs were differentially expressed between these cell populations in the basal state. For example, EDG1 was expressed at elevated levels in CSF-1 M? versus GM-CSF M?, whereas the reverse was true for EDG6. 101 GPCRs showed differential regulation over an LPS time course, with 65 of these profiles being impacted by the basal differentiation state (e.g. GPRC5A, GPRC5B). Only 14 LPS-regulated GPCRs showed asynchronous behavior (divergent LPS regulation) with respect to differentiation status. Thus, the differentiation state primarily affects the magnitude of LPS-regulated expression, rather than causing major reprogramming of GPCR gene expression profiles. Several GPCRs showing differential profiles between CSF-1 M? and GM-CSF M? (e.g. P2RY8, GPR92, EMR3) have not been widely investigated in macrophage biology and inflammation. Strikingly, several closely related GPCRs displayed completely opposing patterns of regulation during differentiation and/or activation (e.g. EDG1 versus EDG6, LGR4 versus LGR7, GPRC5A versus GPRC5B). We propose that selective regulation of GPCR5A and GPCR5B in CSF-1 M? contributes to skewing toward the M2 macrophage phenotype. Our analysis of the GPCR repertoire expressed during primary human monocyte to macrophage differentiation and TLR4-mediated activation provides a valuable new platform for conducting future functional analyses of individual GPCRs in human macrophage inflammatory pathways.
Related JoVE Video
Lysine acetylation in obesity, diabetes and metabolic disease.
Immunol. Cell Biol.
PUBLISHED: 11-15-2011
Show Abstract
Hide Abstract
Histone acetyltransferases (HATs) and histone deacetylases (HDACs) mediate acetylation and deacetylation of histone proteins and transcription factors. There is abundant evidence that these enzymes regulate the acetylation state of many cytoplasmic proteins, including lysine residues in important metabolic enzymes. Lysine acetylation regulates major cellular functions as a common post-transcriptional modification of proteins, conserved from prokaryotes to humans. In this article, we refer to HATs and HDACs broadly as lysine acetyltransferases (KATs) and deacetylases (KDACs). Lysine acetylation is vitally important in both immunological and metabolic pathways and may regulate the balance between energy storage and expenditure. Obesity, type II diabetes and cardiovascular disease (metabolic syndrome) are widely recognised as features of a chronic low-grade inflammatory state, involving significant alterations in primary immunometabolism. Identifying effective therapeutic and preventive options to treat this multi-factorial syndrome has proven to be very challenging, with an emerging focus on developing anti-inflammatory agents that can combat adiposity and metabolic disease. Here, we summarise current evidence and understanding of innate immune and metabolic pathways relevant to adiposity and metabolic disease regulated by lysine acetylation. Developing this understanding in greater detail may facilitate strategic development of novel and enzyme-specific lysine deacetylase modulators that regulate both metabolic and immune systems.
Related JoVE Video
Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats.
Curr Pharm Biotechnol
PUBLISHED: 08-30-2011
Show Abstract
Hide Abstract
The phytoalexin resveratrol (3,4,5-trihydroxy-trans-stilbene) may attenuate cardiovascular disease in man. This study has determined whether treatment with resveratrol (1 mg/kg/day orally) prevented cardiac fibrosis and the decreased cardiovascular function in the DOCA-salt hypertensive rat as a model of human hypertension. Uninephrectomised rats (UNX) administered DOCA (25mg every 4th day sc) and 1% NaCl in drinking water for 28 days developed cardiac and vascular remodelling. In these DOCA-salt rats, resveratrol decreased inflammatory cell infiltration, decreased cardiac fibrosis (left ventricular interstitial and perivascular collagen content) and improved cardiac and vascular function. Resveratrol attenuated other features of cardiovascular remodelling such as increases in systolic blood pressure, left ventricular wet weight, left ventricular wall thickness, diastolic stiffness constant, as well as decreased cardiac contractility and prolonged action potential duration characteristic of DOCA-salt rats. In summary, resveratrol, at a nutritionally relevant dose, prevents or attenuates the adverse changes in the cardiovascular system. We propose that the anti-inflammatory and anti-fibrotic effects of resveratrol are responsible, at least in part, for its amelioration in cardiovascular remodelling in DOCA-salt rats. These actions of resveratrol could play an important role in the protective effects on the human cardiovascular system reported for this constituent of red wine.
Related JoVE Video
Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats.
J. Cardiovasc. Pharmacol.
PUBLISHED: 07-15-2011
Show Abstract
Hide Abstract
The anaphylatoxin C5a generated by activation of the innate immunity complement system is a potent inflammatory peptide mediator through the G-protein-coupled receptor C5aR (CD88) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, T cells, and mast cells. Inflammatory cells infiltrate and initiate the development of fibrosis in the chronically hypertensive heart. In this study, we have investigated whether treatment with a selective C5aR antagonist prevents cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Control and DOCA-salt rats were treated with PMX53 (AcF-[OPdChaWR], 1 mg·kg·d oral gavage) for 32 days; structural and functional changes in cardiovascular system were determined. DOCA-salt hypertension increased leukocyte extravasation into ventricular tissue, increasing collagen deposition and ventricular stiffness; PMX53 treatment attenuated these changes, thereby improving cardiac function. Further, treatment with PMX53 suppressed an increased expression of C5aR in the left ventricle from DOCA-salt rats, consistent with the reduced infiltration of inflammatory cells. Vascular endothelial dysfunction in thoracic aortic rings was attenuated by PMX53 treatment, but systolic blood pressure was unchanged in DOCA-salt rats. In the heart, PMX53 treatment attenuated inflammatory cell infiltration, fibrosis, and ventricular stiffness, indicating that C5aR is critically involved in ventricular remodeling by regulating inflammatory responses in the hypertensive heart.
Related JoVE Video
High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats.
J. Cardiovasc. Pharmacol.
PUBLISHED: 06-02-2011
Show Abstract
Hide Abstract
The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.
Related JoVE Video
Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.
Exp Diabetes Res
PUBLISHED: 05-30-2011
Show Abstract
Hide Abstract
The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.
Related JoVE Video
High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats.
J. Cardiovasc. Pharmacol.
PUBLISHED: 05-17-2011
Show Abstract
Hide Abstract
The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.
Related JoVE Video
Gender differences in metabolic syndrome: a key research issue?
Endocr Metab Immune Disord Drug Targets
PUBLISHED: 02-22-2011
Show Abstract
Hide Abstract
Metabolic syndrome as a clustering of risk factors for diabetes and cardiovascular disease affects both men and women, but with important gender differences. Animal models have been used to understand disease progression and define therapeutic options, but most pre-clinical research on metabolic syndrome is undertaken in males. This opinion piece discusses the differences in male and female physiology that may influence both the development and the responses to pharmacological interventions of metabolic disorders, especially obesity. An appreciation of gender differences should improve the design and usefulness of biomedical experimental research to allow the development of relevant gender-based treatment options for chronic diseases including obesity, metabolic and cardiovascular diseases.
Related JoVE Video
Cardiovascular changes during maturation and ageing in male and female spontaneously hypertensive rats.
J. Cardiovasc. Pharmacol.
PUBLISHED: 02-02-2011
Show Abstract
Hide Abstract
Cardiovascular remodeling leading to heart failure is common in the elderly. Testing effective pharmacological treatment of human heart failure requires a suitable animal model that adequately mimics the human disease state.
Related JoVE Video
A Regenerative Antioxidant Protocol of Vitamin E and ?-Lipoic Acid Ameliorates Cardiovascular and Metabolic Changes in Fructose-Fed Rats.
Evid Based Complement Alternat Med
PUBLISHED: 01-02-2011
Show Abstract
Hide Abstract
Type 2 diabetes is a major cause of cardiovascular disease. We have determined whether the metabolic and cardiovascular changes induced by a diet high in fructose in young adult male Wistar rats could be prevented or reversed by chronic intervention with natural antioxidants. We administered a regenerative antioxidant protocol using two natural compounds: ?-lipoic acid together with vitamin E (?-tocopherol alone or a tocotrienol-rich fraction), given as either a prevention or reversal protocol in the food. These rats developed glucose intolerance, hypertension, and increased collagen deposition in the heart together with an increased ventricular stiffness. Treatment with a fixed combination of vitamin E (either ?-tocopherol or tocotrienol-rich fraction, 0.84?g/kg food) and ?-lipoic acid (1.6?g/kg food) normalized glucose tolerance, blood pressure, cardiac collagen deposition, and ventricular stiffness in both prevention and reversal protocols in these fructose-fed rats. These results suggest that adequate antioxidant therapy can both prevent and reverse the metabolic and cardiovascular damage in type 2 diabetes.
Related JoVE Video
The DOCA-Salt Hypertensive Rat as a Model of Cardiovascular Oxidative and Inflammatory Stress.
Curr Cardiol Rev
PUBLISHED: 09-03-2010
Show Abstract
Hide Abstract
Oxidative stress and inflammation are two sides of the same coin that are intricately combined to elicit a chronic pathophysiological stress state, especially as seen in cardiovascular remodelling. In this review, we argue that administration of deoxycorticosterone acetate (DOCA) and sodium chloride to uninephrectomised rats, defined as DOCA-salt hypertensive rats, provides a reliable animal model of oxidative and inflammatory stress in the cardiovascular system. The supporting evidence includes pathophysiological and biochemical changes together with pharmacological responses to synthetic and natural compounds that lower the concentrations of reactive free radical species and that curtail inflammatory responses in the cardiovascular system.
Related JoVE Video
Green tea attenuates cardiovascular remodelling and metabolic symptoms in high carbohydrate-fed rats.
Curr Pharm Biotechnol
PUBLISHED: 04-15-2010
Show Abstract
Hide Abstract
Excess carbohydrate in the diet may initiate a chronic state of oxidative stress exacerbating the clinical and biochemical symptoms of diet-induced type 2 diabetes, especially glucose intolerance, lipid abnormalities and cardiovascular complications. This study has tested whether green tea, rich in antioxidants, improves both cardiovascular symptoms and glucose intolerance and also reduces oxidative stress in rats fed a high carbohydrate diet. Male 8 week old Wistar rats were fed a diet including fructose and condensed milk (each 40%) for 16 weeks (112 days); control rats were fed corn starch. Green tea-containing food was started from day 1 for the prevention protocol and from day 56 for the reversal protocol. High carbohydrate diet-fed rats showed glucose intolerance, hypertension, mild left ventricular hypertrophy, approximate doubling of cardiac interstitial and perivascular collagen deposition, increased passive diastolic stiffness and increased plasma malondialdehyde concentrations. Administration of green tea to high carbohydrate diet-fed rats prevented and reversed glucose intolerance and the increased systolic blood pressure, left ventricular wet weight, interstitial collagen and passive diastolic stiffness. Plasma malondialdehyde concentrations were also normalized. In summary, treatment with green tea both prevented and reversed the cardiovascular remodelling and metabolic changes seen in high carbohydrate-fed rats suggesting a chronic state of oxidative stress plays a key role in the symptom initiation and progression. Further, green tea may be a useful complementary therapy in diet-induced type 2 diabetes.
Related JoVE Video
Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats.
Br. J. Pharmacol.
PUBLISHED: 02-24-2010
Show Abstract
Hide Abstract
Histone deacetylases (HDACs) silence genes by deacetylating lysine residues in histones and other proteins. HDAC inhibitors represent a new class of compounds with anti-inflammatory activity. This study investigated whether treatment with a broad spectrum HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), would prevent cardiac fibrosis, part of the cardiovascular remodelling in deoxycorticosterone acetate (DOCA)-salt rats.
Related JoVE Video
The cardiovascular nutrapharmacology of resveratrol: pharmacokinetics, molecular mechanisms and therapeutic potential.
Curr. Med. Chem.
PUBLISHED: 02-02-2010
Show Abstract
Hide Abstract
Red wine contains many compounds that may have therapeutic use, including resveratrol (3,4,5-trihydroxytrans-stilbene). Since resveratrol could be administered both in the diet and as a therapeutic agent, defining appropriate concentrations requires understanding of the pharmacokinetics. Resveratrol absorption is rapid but plasma concentrations are low as it is rapidly and efficiently converted into relatively hydrophilic phase-2 conjugates, and metabolites, which are then rapidly excreted via the urine and bile. Resveratrol is an effective antioxidant in vivo by increasing NO synthesis and also maintaining the reduced intracellular redox state via the thioredoxin system. Further, activation of sirtuins (one class of lysine deacetylases) may mediate the cardiovascular responses shown by resveratrol. Studies on animal models of human disease suggest that resveratrol has the potential to decrease cardiovascular symptoms in patients with myocardial infarction, arrhythmias, hypertension, cardiomyopathies, fibrosis, atherosclerosis, thrombosis and diabetes, but, as yet, human clinical trials are rare. Cardioprotection by resveratrol in rodent models may rely on mechanisms producing pharmacological preconditioning in the heart including reducing reactive oxygen species, improving vasorelaxation and angiogenesis, preventing inflammation and apoptosis, delaying atherosclerosis as well as decreasing cardiovascular remodelling. Interventional studies in humans need to be completed before resveratrol can be considered as a standard therapeutic agent. Therefore, future studies should focus on obtaining the level of evidence required to determine whether resveratrol can be added to the list of evidence-based therapies for cardiovascular diseases that includes renin-angiotensin system inhibitors, beta-adrenoceptor antagonists and calcium entry blockers.
Related JoVE Video
Inflammatory lipid mediators in adipocyte function and obesity.
Nat Rev Endocrinol
PUBLISHED: 01-26-2010
Show Abstract
Hide Abstract
Survival of multicellular organisms depends on their ability to fight infection, metabolize nutrients, and store energy for times of need. Unsurprisingly, therefore, immunoregulatory and metabolic mechanisms interact in human conditions such as obesity. Both infiltrating immunoinflammatory cells and adipocytes play critical roles in the modulation of metabolic homeostasis, so it is important to understand factors that regulate both adipocyte and immune cell function. A currently favored paradigm for obesity-associated metabolic dysfunction is that chronic macronutrient and/or lipid overload (associated with adiposity) induces cellular stress that initiates and perpetuates an inflammatory cycle and pathophysiological signaling of immunoinflammatory cells and adipocytes. Many lipid mediators exert their biological effects by binding to cognate receptors, such as G-protein-coupled receptors and Toll-like receptors. This process is tightly regulated under normal physiological conditions, and any disruption can initiate disease processes. Observations that cellular lipid loading (associated with adiposity) initiates inflammatory events has encouraged studies on the role of lipid mediators. In this review, we speculate that lipid mediators act on important immune receptors to induce low-grade tissue inflammation, which leads to adipocyte and metabolic dysfunction.
Related JoVE Video
L-carnitine attenuates cardiac remodelling rather than vascular remodelling in deoxycorticosterone acetate-salt hypertensive rats.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 11-11-2009
Show Abstract
Hide Abstract
L-carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p < 0.05 versus DOCA-salt). Uninephrectomized rats administered DOCA (25 mg every 4th day s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular remodelling shown as systolic hypertension, left ventricular hypertrophy, increased thoracic aortic and left ventricular wall thickness, increased left ventricular inflammatory cell infiltration together with increased interstitial collagen and increased passive diastolic stiffness and vascular dysfunction with increased plasma malondialdehyde concentrations. Treatment with L-carnitine (1.2% in food; 0.9 mg/g/day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169 +/- 2; + L-carnitine 148 +/- 6# mmHg), decreased left ventricular wet weights (DOCA-salt 3.02 +/- 0.07; + L-carnitine 2.72 +/- 0.06# mg/g body-wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA-salt 14.4 +/- 0.2; + L-carnitine 8.7 +/- 0.5# % area), reduced diastolic stiffness constant (DOCA-salt 26.9 +/- 0.5; + L-carnitine 23.8 +/- 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA-salt 26.9 +/- 0.8; + L-carnitine 21.2 +/- 0.4# micromol/l) without preventing endothelial dysfunction. L-carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA-salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA-salt rats, underlying the relatively selective cardiac responses to L-carnitine treatment.
Related JoVE Video
Evaluation of the chronic complications of diabetes in a high fructose diet in rats.
Indian J. Biochem. Biophys.
PUBLISHED: 04-21-2009
Show Abstract
Hide Abstract
The increasing prevalence of type 2 diabetes is associated with increasing health costs, especially for the treatment of cardiovascular disease. The development of new treatment modalities requires animal models that mimic the range of pathophysiological changes seen in diabetic humans. Dietary fructose intake has been linked to the increase in insulin resistance as part of the metabolic syndrome; fructose-fed rats develop type 2 diabetes. This study has characterized the cardiovascular changes in young adult male Wistar rats fed a 61% fructose diet for 16 weeks. Our results extend the reported changes of hypertension, lipid abnormalities, impaired glucose tolerance and impaired oxidative defense to include ventricular dilatation with hypertrophy and decreased contractile function, together with increased inflammatory cell infiltration into the ventricular myocardium, resulting in excessive collagen deposition and an increased stiffness of the left ventricle. However, endothelial dysfunction, tactile allodynia as a symptom of peripheral neuropathy and retinopathy are not present in these rats, in contrast to the streptozotocin-induced model of type 1 diabetes. Thus, fructose feeding mimics many, but not all, of the symptoms of type 2 diabetes in humans.
Related JoVE Video
Is mycophenolate more than just an immunosuppressant?--An overview.
Indian J. Biochem. Biophys.
PUBLISHED: 04-21-2009
Show Abstract
Hide Abstract
The development of immunosuppressant compounds, such as cyclosporine and tacrolimus was crucial to the success of transplant surgery and for treatment of autoimmune diseases. However, immunosuppressant therapy may increase the concentrations of reactive oxygen species (ROS), inducing oxidative damage such as an increased vascular damage. The major source of ROS in the vascular endothelial cells is NADPH oxidase. The subunit structure and function of this enzyme complex in vascular cells differs from that in phagocytic leucocytes. The enzyme subunits Nox1, Nox2 and Nox4 are only found in vascular cells. The GTP-dependent protein subunit Rac 1 needs to be activated for this enzyme to function. Inhibiting this protein subunit should reduce NADPH oxidase-induced oxidative stress. In the cardiovascular system, oxidative stress is observed as hypertension, hypertrophy, fibrosis, conduction abnormalities and endothelial dysfunction, as well as cardiac allograft vasculopathy in transplant patients. In contrast to cyclosporine and tacrolimus, the immunosuppressant mycophenolate inhibits the Rac 1 subunit thus inhibiting NADPH oxidase in the vasculature. This may reduce oxidative stress, prevent the development of cardiac allograft vasculopathy, decrease the deterioration of vascular function and improve cardiovascular function chronically in transplant patients. This overview discusses whether this antioxidant immunosuppressive property could translate into a more general protective role for mycophenolate in the prevention of cardiovascular disease.
Related JoVE Video
Potential health benefits of Indian spices in the symptoms of the metabolic syndrome: a review.
Indian J. Biochem. Biophys.
PUBLISHED: 01-13-2009
Show Abstract
Hide Abstract
Spices used in Indian cooking have a long history of use as medicines to prevent and treat diseases. Many studies have confirmed that spices can be useful medicines, but the major challenge is now to provide scientific evidence and plausible mechanisms for their therapeutic responses. This review focuses on the therapeutic potential of Indian spices to treat multiple symptoms of the metabolic syndrome such as insulin resistance, diabetes, obesity, altered lipid profile and hypertension. The metabolic syndrome is prevalent and has become an important financial burden to the healthcare system in both developed and developing countries. Inflammation and oxidative stress have been proposed as initiators of the metabolic syndrome, especially of insulin resistance. Natural products with anti-inflammatory and anti-oxidant properties are found in spices. Adequate doses of these compounds may be effective in treating the metabolic syndrome. Testing these potential treatments requires adequate animal models, usually rodents, so the limitations of these models are important. Furthermore, this review highlights the need for adequate legislation and regulation to ensure the safety and success of evidence-based functional foods and nutraceuticals. Keywords: Spices, Diabetes, Cardiovascular disease, Metabolic syndrome, Inflammation, Oxidative stress,
Related JoVE Video
C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling.
FASEB J.
Show Abstract
Hide Abstract
Mammalian survival depends on metabolizing nutrients, storing energy, and combating infection. Complement activation in blood triggers energy-depleting immune responses to fight infections. Here we identify surprising energy-conserving roles for complement proteins C5a and C3a and their receptors, C5aR and C3aR, roles that are contraindicated in complement biology. Rats fed a high-carbohydrate high-fat diet developed obesity, visceral adiposity, adipose inflammation, glucose/insulin intolerance, and cardiovascular dysfunction that correlated with increased plasma C3a, adipose C5aR, and C3aR. These in vivo changes were dramatically attenuated by receptor-selective antagonists of either C5aR (5 mg/kg/d p.o.) or C3aR (30 mg/kg/d p.o.), which both reduced proinflammatory adipokines and altered expression of inflammatory genes in adipose tissue. In vitro C5a and C3a (100 nM) exhibited novel insulin-like effects on 3T3-L1 adipocytes, promoting energy conservation by increasing glucose and fatty acid uptake while inhibiting cAMP signaling and lipolysis, and induced PGE(2) release from macrophages, effects all blocked by each respective antagonist (10 ?M). These studies reveal important new links between complement signaling and metabolism, highlight new complement functions on adipocytes and in adipose tissue, demonstrate how aberrant immune responses may exacerbate obesity and metabolic dysfunction, and show that targeting C3aR or C5aR with antagonists is a new strategy for treating metabolic dysfunction.
Related JoVE Video
An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats.
Diabetes
Show Abstract
Hide Abstract
Obesity, type 2 diabetes, and cardiovascular disease correlate with infiltration to adipose tissue of different immune cells, with uncertain influences on metabolism. Rats were fed a diet high in carbohydrates and saturated fats to develop diet-induced obesity over 16 weeks. This nutritional overload caused overexpression and secretion of phospholipase A(2) group IIA (pla2g2a) from immune cells in adipose tissue rather than adipocytes, whereas expression of adipose-specific phospholipase A(2) (pla2g16) was unchanged. These immune cells produce prostaglandin E(2) (PGE(2)), which influences adipocyte signaling. We found that a selective inhibitor of human pla2g2a (5-(4-benzyloxyphenyl)-(4S)-(phenyl-heptanoylamino)-pentanoic acid [KH064]) attenuated secretion of PGE(2) from human immune cells stimulated with the fatty acid, palmitic acid, or with lipopolysaccharide. Oral administration of KH064 (5 mg/kg/day) to rats fed the high-carbohydrate, high-fat diet prevented the overexpression of pla2g2a and the increased macrophage infiltration and elevated PGE(2) concentrations in adipose tissue. The treatment also attenuated visceral adiposity and reversed most characteristics of metabolic syndrome, producing marked improvements in insulin sensitivity, glucose intolerance, and cardiovascular abnormalities. We suggest that pla2g2a may have a causal relationship with chronic adiposity and metabolic syndrome and that its inhibition in vivo may be a valuable new approach to treat obesity, type 2 diabetes, and metabolic dysfunction in humans.
Related JoVE Video
Towards isozyme-selective HDAC inhibitors for interrogating disease.
Curr Top Med Chem
Show Abstract
Hide Abstract
Histone deacetylase (HDAC) enzymes have emerged as promising targets for the treatment of a wide range of human diseases, including cancers, inflammatory and metabolic disorders, immunological, cardiovascular, and infectious diseases. At present, such applications are limited by the lack of selective inhibitors available for each of the eighteen HDAC enzymes, with most currently available HDAC inhibitors having broad-spectrum activity against multiple HDAC enzymes. Such broad-spectrum activity maybe useful in treating some diseases like cancers, but can be detrimental due to cytotoxic side effects that accompany prolonged treatment of chronic diseased states. Here we summarize progress towards the design and discovery of HDAC inhibitors that are selective for some of the eleven zinc-containing classical HDAC enzymes, and identify opportunities to use such isozyme-selective inhibitors as chemical probes for interrogating the biological roles of individual HDAC enzymes in diseases.
Related JoVE Video
Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats.
Basic Clin. Pharmacol. Toxicol.
Show Abstract
Hide Abstract
Acute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system because of mineralocorticoid receptor activation, as morphine increases plasma corticosterone concentrations. Morphine-dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalised in morphine-dependent rats treated with spironolactone (50 mg/kg/day) from days 14-21. These results suggest that morphine dependence induces ventricular remodelling and increased oxidative stress that can be prevented by the mineralocorticoid receptor antagonist, spironolactone.
Related JoVE Video
Ligand mediated valence fluctuation of copper in new hybrid materials constructed from decavanadate and a Cu(1,10-phenanthroline) complex.
Dalton Trans
Show Abstract
Hide Abstract
Two new organic hybrid materials [H4V10O28][CuCl(H2O)2(1,10-phenanthroline)]2·4H2O (V10O28-CuCl-phen) and [H4V10O28][Cu(H2O)3(1,10-phenanthroline)]2·4H2O (V10O28-CuO-phen) were synthesized at room temperature. The effect of the presence and absence of AlCl3 on the single crystal growth of the two compounds was studied. The compounds were characterized using single crystal X-ray diffraction (XRD), scanning electron microscopy, energy dispersive spectroscopy, infra-red spectroscopy and thermogravimetric analysis. XRD studies on selected single crystals suggest that the compounds consist of supramolecular 3D layer structures constructed from a tetra-protonated [V10O28] unit and the organometallic complex Cu(1,10-phen) with Cl and 2H2O molecules in the presence of AlCl3 in V10O28-CuCl-phen and with 3H2O molecules in V10O28-CuO-phen which was confirmed by TGA studies. Both compounds crystallize in the triclinic space group P1[combining macron]: a = 8.3886(3) Å, b = 10.4266(4) Å, c = 13.5860(5) Å, ? = 92.440(2)°, ? = 92.315(2)°, ? = 98.160(2)° for V10O28-CuCl-phen and a = 8.3733(5) Å, b = 10.4132(6) Å, c = 13.5904(8) Å, ? = 92.295(4)°, ? = 92.331(2)°, ? = 98.086(4)° for V10O28-CuO-phen. Magnetic measurements suggest that Cu exists in magnetic +2 oxidation state in V10O28-CuCl-phen and non-magnetic +1 oxidation state in V10O28-CuO-phen.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.