Biomedical subjects
Publications and source records attributed to Himanshu Gupta.
Biopsy of cardiac tumors to obtain a tissue diagnosis has been performed under echocardiographic (transthoracic or transesophageal) or fluoroscopic guidance. We report successful transjugular biopsy of a right atrial mass using intracardiac echocardiographic guidance.
PURPOSE OF REVIEW: Recent publications related to the potential use of synthetic peptides for the management of lipid disorders and their vascular complications are reviewed. RECENT FINDINGS: The potential use of synthetic peptides for the management of lipid disorders and their vascular complications has emerged in recent years. These peptides are models of apolipoproteins, but are much smaller in size than the apolipoproteins. Oral peptides that improve the antiinflammatory properties of HDLs have been shown to potently inhibit atherosclerosis in mouse models. Injection of a peptide with a class A amphipathic helix in a rat model of diabetes dramatically reduced endothelial sloughing and improved vasoreactivity. Injected synthetic peptides have also been described that dramatically lower plasma cholesterol and restore endothelial function in a rabbit model of familial hypercholesterolemia. These studies suggest the therapeutic potential for synthetic peptides in the management of lipid disorders and their vascular complications. SUMMARY: Synthetic peptides much smaller than exchangeable human plasma apolipoproteins but with physical and chemical characteristics similar to the plasma apolipoproteins have shown promise in the management of lipid disorders and their vascular complications in animal models. The initial success of these animal studies suggests that synthetic peptides have the potential to emerge as a new therapeutic class of agents in the management of patients with lipid disorders.
In optimization studies including multi-objective optimization, the main focus is placed on finding the global optimum or global Pareto-optimal solutions, representing the best possible objective values. However, in practice, users may not always be interested in finding the so-called global best solutions, particularly when these solutions are quite sensitive to the variable perturbations which cannot be avoided in practice. In such cases, practitioners are interested in finding the robust solutions which are less sensitive to small perturbations in variables. Although robust optimization is dealt with in detail in single-objective evolutionary optimization studies, in this paper, we present two different robust multi-objective optimization procedures, where the emphasis is to find a robust frontier, instead of the global Pareto-optimal frontier in a problem. The first procedure is a straightforward extension of a technique used for single-objective optimization and the second procedure is a more practical approach enabling a user to set the extent of robustness desired in a problem. To demonstrate the differences between global and robust multi-objective optimization principles and the differences between the two robust optimization procedures suggested here, we develop a number of constrained and unconstrained test problems having two and three objectives and show simulation results using an evolutionary multi-objective optimization (EMO) algorithm. Finally, we also apply both robust optimization methodologies to an engineering design problem.
A patient with a history of Hodgkin's lymphoma presented with recurrent left pleural effusions and dyspnea on exertion 27 years after radiation therapy. Further evaluation disclosed suspected radiation-induced constrictive pericarditis, aortic stenosis and regurgitation, and severe coronary artery disease. He underwent successful 3-vessel coronary artery bypass grafting, aortic valve replacement, and pericardiectomy.
Levels of high density lipoprotein (HDL) and its major protein component, apolipoprotein (apo) A-I, are strongly inversely correlated to risk of atherosclerosis and other vascular diseases. A number of properties of apo A-I may contribute to this protection, including removal of cholesterol from peripheral tissues to the liver (reverse cholesterol transport), anti-inflammatory and anti-oxidative activities, and modulation of vascular function. Apo A-I has lipid-associating domains that form class A amphipathic helices. Peptide analogs that have no sequence homology to the domains in apo A-I but possess the class A motif have been shown to not only associate with phospholipid but also mimic several of the functional properties of apo A-I. Peptide 4F, with four phenylalanines on the non-polar face, was found to be maximally effective in mimicking the positive qualities of apo A-I; this peptide inhibited atherosclerosis, reduced inflammation and oxidation, and improved vascular function in a number of animal models, and when synthesized with D-amino acids is orally bioavailable. Several other classes of peptide mimetics are now being studied, and may contribute to our understanding of the functions of apo E and apo J. The use of peptide mimetics to study apolipoprotein function has proved to be a powerful tool, and may lead to novel therapeutic agents in the prevention of atherosclerosis and other vascular diseases.
Previous studies suggest that high-density lipoprotein and apoAI inhibit lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes. Incubation of cells with LPS and L-4F (1 to 50 microg/mL) reduced THP-1 adhesion in a concentration-dependent manner. This response was associated with a significant reduction in the synthesis of cytokines, chemokines, and adhesion molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast to LPS treatment, L-4F did not inhibit IL-1beta- or tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L-4F on LPS induction of inflammatory markers was associated with reduced binding of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture medium were fractionated by fast protein liquid chromatography and were localized to the same fractions, suggesting a physical interaction between these molecules. Proinflammatory responses to LPS are associated with the binding of lipid A to cell surface receptors. The current studies demonstrate that L-4F reduces the expression of inflammatory markers induced by LPS and lipid A and suggest that apoAI peptide mimetics may be useful in the treatment of inflammation associated with endotoxemia.
BACKGROUND: These studies were designed to determine whether the dual-domain peptide with a class A amphipathic helix linked to the receptor-binding domain of apolipoprotein (apo) E (Ac-hE-18A-NH2) possesses both antidyslipidemic and antiinflammatory properties. METHODS AND RESULTS: A single bolus (15 mg/kg IV) of Ac-hE-18A-NH2 that contains LRKLRKRLLR (141- to 150-residue region of apo E) covalently linked to apo A-I mimetic peptide 18A not only reduced plasma cholesterol levels (baseline, 562+/-29.0 mg/dL versus 287.7+/-22.0 mg/dL at 18 hours, P<0.001) in the Watanabe heritable hyperlipidemic rabbit model but also significantly improved arterial endothelial function. This improvement was associated with a reduction in 2 markers of oxidative stress. First, the plasma lipid hydroperoxide content was reduced significantly, an effect associated with a 5-fold increase in HDL paraoxonase activity. Second, the formation of superoxide anion, a scavenger of nitric oxide, was also significantly reduced in arteries of these animals. CONCLUSIONS: Because dyslipidemia and endothelial dysfunction are common features of the atherosclerotic disease process, this unique dual-domain peptide has ideal composite properties that ameliorate key contributory factors to atherosclerosis.
Patients with ischemic heart disease may have left ventricular (LV) dysfunction due to reversible or irreversible causes. The ability to distinguish viable myocardium with dysfunction due to a reversible etiology (hibernation, stunning) from nonviable scar is critical for determining proper management of the patient. Cardiovascular magnetic resonance (CMR) is a technique that has been established to be useful for the detection of myocardial viability and advancements in the field promise to further increase its utility. In this review we describe the features of CMR that make it suited for this purpose and outline promising developments that may soon make CMR the reference standard for viability assessment.
Though morphine remains the most powerful drug for treating pain, its effectiveness is limited by the development of tolerance and dependence. The mechanism underlying development of tolerance to morphine is still poorly understood. One of the factors could be an alteration in the number of micro-receptors within specific parts of the nervous system. However, reports on changes in the micro-opioid receptor density in the spinal cord after chronic morphine administration are conflicting. Most of the studies have used subcutaneously implanted morphine pellets to produce tolerance. However, it does not simulate clinical conditions, where it is more common to administer morphine at intervals, either by injections or orally. In the present study, rats were made tolerant to morphine by injecting increasing doses of morphine (10-50 mg/kg, subcutaneously) for five days. In vitro tissue autoradiography for localization of micro-receptor in the spinal cord was done using [3H]-DAMGO. As compared to the spinal cord of control rats, the spinal cord of tolerant rats showed an 18.8% increase or up-regulation in the density of micro-receptors in the superficial layers of the dorsal horn. This up-regulation of micro-receptors after morphine tolerance suggests that a fraction of the receptors have been rendered desensitized, which in turn could lead to tolerance
BACKGROUND: Little is known about the impact of post-menopausal hormone therapy on remnant-like particle (RLP) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women. METHODS: RLP cholesterol and triglyceride levels were measured at baseline and 3 months after randomization in 397 post-menopausal women enrolled in The Women's Angiographic Vitamin & Estrogen (WAVE) trial. Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression. Coronary angiography was performed at baseline and after a mean of 2.9 years. Changes in minimal and average luminal diameter were modeled with multivariate linear regression, clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death) with multiple logistic regression. RESULTS: The mean subject age was 65 years, 66% of subjects were white, 18% of subjects smoked, most subjects were overweight or obese, and 35% of subjects had diabetes mellitus. RLP cholesterol (0.277 +/- 0.254 mmol/L) and triglyceride (0.386 +/- 0.552 mmol/L) levels corresponded approximately to the 90th percentile in women in the Framingham study. RLP levels did not change significantly with hormone therapy. RLP levels at baseline, changes in RLP levels, and on treatment RLP levels did not relate to angiographic changes or clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death). CONCLUSIONS: RLP levels were high among post-menopausal women enrolled in the WAVE study, were not affected by hormone therapy, and did not relate to angiographic progression of coronary artery disease or clinical outcomes.
We report an adult patient with a patent ductus arteriosus in whom live three-dimensional transthoracic echocardiography provided comprehensive assessment of the morphology and pathophysiology of the lesion.
We report an elderly patient in whom a thrombus in the distal left pulmonary artery was shown by transesophageal echocardiography to extend and produce obstruction of the descending lobar branches as well as dilatation of the left bronchial artery.
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