PubMed Health⌕ Search

Biomedical subjects

Kamal F Badr

Publications and source records attributed to Kamal F Badr.

8 recordsLinked to original sources
PubMed2006

Measuring filtration function in clinical practice.

PURPOSE OF REVIEW: The global prevalence of chronic kidney disease is increasing, as are its complications. Central to the diagnosis, evaluation and management of chronic kidney disease is the estimation of glomerular filtration rate. This article summarizes the various equations used to estimate filtration function and the performance of each in clinical practice. RECENT FINDINGS: During the past year the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, continued to receive much interest. Many studies have compared the performance of the Modification of Diet in Renal Disease Study equation and the Cockcroft-Gault equation. The performance of these equations in various patient populations, such as patients with advanced heart failure, diabetic patients, renal transplantation patients, and the healthy general population, has been extensively studied. Overall, the Modification of Diet in Renal Disease Study equation has had an acceptable validity and has outperformed the Cockcroft-Gault equation in the various populations, but with some limitations that the physician should account for in clinical practice. SUMMARY: The use of the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, should be implemented more frequently in clinical practice. An ever increasing number of studies has validated its use in different patient populations.

Cardiovascular Diseases↗
PubMed2004

Molecular pharmacology of isoprostanes in vascular smooth muscle.

Isoprostanes are marker of lipid peroxidation and are produced after free-radical attack of membrane lipids. In addition, they are biologically active and are essentially vaso- and broncho-constrictor. Their smooth muscle constrictor actions are closely linked to the activation of the thromboxane A(2) receptor, but also involve a distinct receptor not yet identified. The response of vascular smooth muscle to isoprostanes is subclass-specific (F-series versus E-series isoprostanes) and cell- and species-related. In this review, we will address the vascular actions of isoprostanes and their possible role in vascular physiology and pathophysiology.

Animals↗
PubMed2004

Cytokine imbalance in acute coronary syndrome.

The excessive mortality of coronary heart disease is attributed primarily to rupture and thrombotic transformation of the atherosclerotic plaque. Inflammation plays a critical role in plaque destabilization and vulnerability. Inflammation is not confined to the culprit segment but is convincingly widespread in the coronary and remote vascular beds. Systemic inflammatory, thrombotic and hemodynamic factors are relevant to the pathological and clinical outcome. In addition to their fundamental role in thrombosis, there is ample evidence that platelets contribute significantly to promoting plaque inflammation. A new paradigm of unbalanced cytokine-mediated inflammation is emerging, providing diagnostic and therapeutic opportunity for intervention. Amplifying intrinsic anti-inflammatory mechanisms constitutes attractive avenues for future investigation.

Acute Disease↗
PubMedDate not supplied

Isoprostanes and the kidney.

Isoprostanes are not mere bystanders of oxidative injury, but possess potent biological activity and may thus contribute to the pathophysiology of various disorders associated with an increase in free radical formation. 15-F2t-IsoP (8-iso-prostaglandin F2) and 15-E2t-IsoP (8-iso-prostaglandin E2), two of the most abundant isoprostanes, are potent vasoconstrictors in various vascular beds, including the kidney. Since their discovery, numerous studies have aimed to define the receptors through which isoprostanes exert their effects. Whether the thromboxane receptor and/or other prostaglandin receptors mediate the actions of isoprostanes, or whether these compounds interact with their own unique receptors, remains to be clarified. Regardless of their exact mode of action, isoprostanes are being implicated in the pathophysiology of a variety of diseases, and their discovery might give rise to novel therapies for these diseases. Here we describe early studies that defined the vasoactive properties of isoprostanes in the kidney, and subsequent discoveries relating to their renal actions and pathophysiologic significance.

Animals↗
PubMedDate not supplied

Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to the 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes (LT) from arachidonic acid. We have shown that FLAP antagonist administration decreased proteinuria in glomerulonephritic patients. In this follow-up study, we assessed the role for FLAP in a rat model of streptozotocin-induced diabetic nephropathy. METHODS: Diabetic rats were treated for 4 weeks with FLAP (BAY X-1005, 200 mg/kg) or 5-LO (Zileuton, 80 mg/Kg) antagonists. Proteinuria, renal function and LT production was assessed. We also determined protein permeability of cultured glomerular endothelial cells (which possess no 5-LO) by measuring their permeability to radiolabeled albumin with and without FLAP antagonists. RESULTS: FLAP mRNA levels increased dramatically in glomeruli from diabetic animals compared to controls. Inhibition of FLAP (but not inhibition of 5-LO) reduced proteinuria, with no effect on estimated glomerular filtration rate. Interestingly, diabetes-induced rises in urinary excretion and glomerular production of leukotrienes were not modified by the inhibitors. Increased FLAP expression in glomerular endothelial cells in culture was associated with an increase in albumin permeability, and this increase was abolished by FLAP antagonists. On the other hand, addition of LTA(4) led to increases in leukotriene formation and in permeability. This increase in permeability was also reduced by co-incubation with FLAP antagonists, whereas the increase in leukotriene synthesis was not modified. CONCLUSIONS: These results suggest a role for FLAP other than the activation of 5-LO, possibly in protein handling, and point to FLAP antagonists as anti-proteinuric agents.

Analysis of Variance↗
PubMedDate not supplied

Increased 5-lipoxygenase activating protein in immune-mediated experimental nephritis.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid. METHODS: We investigated the localization of FLAP in a rat model of accelerated anti-glomerular basement membrane nephritis and protein expression in cultured rat glomerular endothelial cells. RESULTS: As expected, 5-LO staining was intense and localized exclusively to perinuclear region and inside the nucleus of leukocytes and macrophages. In these cells, FLAP immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was also observed in glomerular endothelial cells in early experimental glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5-LO protein. FLAP protein was regulated in glomerular endothelial cells by the proinflammatory cytokine, interferon-gamma, in a dose-dependent manner. CONCLUSION: The unexpected discovery of FLAP in glomerular endothelial cells in this model of glomerulonephritis, coupled with our demonstration that oral FLAP antagonist therapy reduces proteinuria in human glomerulonephritis and animal models of diabetes, provides further impetus to examine the role of this pro-inflammatory protein in glomerular immune injury.

5-Lipoxygenase-Activating Proteins↗