Management of lower-extremity venous thromboembolism: An updated review.

According to the 2021 updated guidelines of the American College of Chest Physicians, the location of venous thromboembolism, the severity of symptoms, the risk of thrombus extension vs that of bleeding, and comorbidities all affect the decision to treat, the choice of anti-thrombotic agent, and the duration of therapy. In patients with isolated distal deep vein thrombosis without high-risk features, monitoring progression is recommended over initiating anticoagulation. However, treatment of proximal deep vein thrombosis with anticoagulation is strongly recommended by the guidelines.

Biospecimen Repositories in Low- and Middle-Income Countries: Insights From an American University of Beirut and Memorial Sloan Kettering Collaboration.

Purpose: Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon.

VEGF-A: A Novel Mechanistic Link Between CYP2C-Derived EETs and Nox4 in Diabetic Kidney Disease.

Unlabelled: Diabetes is associated with decreased epoxyeicosatrienoic acid (EET) bioavailability and increased levels of glomerular vascular endothelial growth factor A (VEGF-A) expression. We examined whether a soluble epoxide hydrolase inhibitor protects against pathologic changes in diabetic kidney disease and whether the inhibition of the VEGF-A signaling pathway attenuates diabetes-induced glomerular injury. We also aimed to delineate the cross talk between cytochrome P450 2C (CYP2C)-derived EETs and VEGF-A.

Modulation of Neuro-Inflammatory Signals in Microglia by Plasma Prekallikrein and Neuronal Cell Debris.

Microglia, the resident phagocytes of the central nervous system and one of the key modulators of the innate immune system, have been shown to play a major role in brain insults. Upon activation in response to neuroinflammation, microglia promote the release of inflammatory mediators as well as promote phagocytosis. Plasma prekallikrein (PKall) has been recently implicated as a mediator of neuroinflammation; nevertheless, its role in mediating microglial activation has not been investigated yet.

Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals.

Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this study, we employed tandem LC-MS/MS to identify protein signatures that encompass protein abundance in RASMC treated with BK or leptin followed by systems biology analyses to gain insight into the biological pathways and processes linked to vascular remodeling.

Modulation of proteomic and inflammatory signals by Bradykinin in podocytes.

Podocyte damage is one of the hallmarks of diabetic nephropathy leading to proteinuria and kidney damage. The underlying mechanisms of podocyte injury are not well defined. Bradykinin (BK) was shown to contribute to diabetic kidney disease.

Heteromerization fingerprints between bradykinin B2 and thromboxane TP receptors in native cells.

Bradykinin (BK) and thromboxane-A2 (TX-A2) are two vasoactive mediators that modulate vascular tone and inflammation via binding to their cognate "class A" G-protein coupled receptors (GPCRs), BK-B2 receptors (B2R) and TX-prostanoid receptors (TP), respectively. Both BK and TX-A2 lead to ERK1/2-mediated vascular smooth muscle cell (VSMC) proliferation and/or hypertrophy. While each of B2R and TP could form functional dimers with various GPCRs, the likelihood that B2R-TP heteromerization could contribute to their co-regulation has never been investigated.

Proteome profiling in the aorta and kidney of type 1 diabetic rats.

Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats.

Mechanisms of bradykinin-induced expression of connective tissue growth factor and nephrin in podocytes.

Diabetic nephropathy (DN) is the main cause of morbidity and mortality in diabetes and is characterized by mesangial matrix deposition and podocytopathy, including podocyte loss. The risk factors and mechanisms involved in the pathogenesis of DN are still not completely defined. In the present study, we aimed to understand the cellular mechanisms through which activation of B2 kinin receptors contribute to the initiation and progression of DN.

Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most serious complications of type I and type II diabetes. DN is characterized by hyperfiltration, hypertrophy, extracellular matrix accumulation, and proteinuria. This advances into renal fibrosis and loss of renal function.

20-HETE and EETs in diabetic nephropathy: a novel mechanistic pathway.

Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanisms leading to tubular injury is not well defined.

Effects of weight reduction regimens and bariatric surgery on chronic kidney disease in obese patients.

Increasing evidence nowadays is showing that obesity by itself, independent of other comorbidities like diabetes and hypertension, is associated with renal functional changes and structural damage. Intentional weight loss demonstrates beneficial reduction in proteinuria and albuminuria in patients with mild to moderate chronic kidney disease, particularly those whose renal damage is likely induced by obesity. The safety of some weight loss interventions, particularly the use of high-protein diets and/or medications, is questionable in this population due to the lack of well-designed randomized controlled studies reporting on their efficacy or harm.

Overview of the physiology and pathophysiology of leptin with special emphasis on its role in the kidney.

The adipocyte product leptin is a pleiotropic adipokine and hormone, with a role extending beyond appetite suppression and increased energy expenditure. This review summarizes the biology of the leptin system and the roles of its different receptors in a multitude of cellular functions in different organs, with special emphasis on the kidney. Leptin's physiological functions as well as deleterious effects in states of leptin deficiency or hyperleptinemia are emphasized.

Glomerular hyperfiltration and proteinuria in transfusion-independent patients with β-thalassemia intermedia.

Background/aims: Renal manifestations have been described in β-thalassemia major and were attributed to transfusional iron overload and chelation therapy. Patients with the milder phenotype, β-thalassemia intermedia (TI), remain largely transfusion and iron chelation independent while enduring a chronic hemolytic anemia and primary iron overload. Data on renal function in patients with TI is lacking.

Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes.

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B(2)-receptors (B(2)R) in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B(2)R knockout (B(2)R(-/-)) mice.

Heat shock protein 90 inhibitor attenuates renal fibrosis through degradation of transforming growth factor-β type II receptor.

The accumulation of extracellular matrix proteins in the interstitial area is the final common feature of chronic kidney diseases. Accumulating evidence suggests that transforming growth factor (TGF)-β1 promotes the development of renal fibrosis. Heat shock protein (Hsp) 90 inhibitors have been shown to repress TGF-β1 signaling, but whether they inhibit renal fibrosis is unknown.

Emerging therapies for diabetic nephropathy patients: beyond blockade of the Renin-Angiotensin system.

Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been glycemic control and blood pressure lowering using agents blocking the renin-angiotensin system. Clinical trials are currently under way using novel agents for the treatment of patients with diabetic nephropathy.

Angiogenic factors.

Diabetic nephropathy (DN) is in essence a microvascular disease that develops as a result of a confluence of hemodynamic and metabolic perturbations. Angiogenic factors are prime candidates to explain the vascular and pathologic findings of DN; however, analysis of their pathophysiology shows that they have a constellation of effects on the glomerulus that go beyond angiogenesis. Vascular endothelial growth factor (VEGF) is an exemplary candidate for fulfilling the criteria for Koch's postulate as an etiologic agent of the glomerulopathy in diabetes.

Uremia induces functional incompetence of bone marrow-derived stromal cells.

Background: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular diseases (CVD). We hypothesized that inadequate angiogenic response in uremic patients could result from dysfunction of bone marrow-derived stromal cells [mesenchymal stem cells (MSCs)].

Methods: We investigated whether MSCs are functionally competent in uremia induced by partial kidney ablation in C57Bl/6J mice.

The cardiorenal syndrome in diabetes mellitus.

The cardiorenal syndrome in patients with diabetes mellitus represents a systemic condition that affects both the cardiovascular and renal systems. Diabetes is a well established risk factor for cardiovascular disease (CVD), and a significant proportion of diabetic patients go on to develop clinically significant nephropathy. In the diabetic state the kidney is involved by progressive sclerosis/fibrosis and proteinuria, due most likely to overactivity of the transforming growth factor-beta system and, to some extent, the vascular endothelial growth factor system, respectively.

A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity.

Background: Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years' detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon.

Vascular endothelial growth factor and diabetic nephropathy.

The field of vascular endothelial growth factor (VEGF) has recently witnessed a surge of research into its role in diabetic kidney disease. Based on its credentials as a potent inducer of vasopermeability and angiogenesis, podocyte-derived VEGF is believed to participate in the glomerular capillary hyperpermeability of macromolecules that potentially underlies the pathogenesis of diabetic albuminuria. The evidence for VEGF's role is relatively straightforward in animal models of diabetes, establishing that VEGF is upregulated in the diabetic kidney, that VEGF alone reproduces some aspects of diabetic glomerulopathy, and that antagonism of VEGF attenuates diabetic albuminuria and other associated features of the podocytopathy.