[Optimal use of proton pump inhibitors in primary care].

Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence; they can have an important impact on the patient's quality of life and generate a considerable health care cost. Proton pump inhibitors are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review provides primary care clinicians with best practice guidelines for optimal use of these drugs.

Optimal use of proton pump inhibitors for treating acid peptic diseases in primary care.

Heartburn, reflux and epigastric pain are frequently encountered symptoms in primary care medicine. Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence, can have important impact on patient quality of life and represent a considerable health care cost. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases.

Vascular calcification is associated with cortical bone loss in chronic renal failure rats with and without ovariectomy: the calcification paradox.

Background: Increased bone loss has been associated with the development of vascular calcification in patients with chronic renal failure (CRF). In this study, the effect of impaired bone metabolism on aortic calcifications was investigated in uremic rats with or without ovariectomy.

Methods: CRF was induced by administration of a 0.

Prevention of vascular calcification: is pyrophosphate therapy a solution?

Pyrophosphate, a ubiquitous small-molecule inhibitor of mineralization abundantly present in the extracellular environment, binds to calcium and mineral surfaces to inhibit crystal growth. O'Neill and colleagues show in uremic rats that systemic administration of pyrophosphate prevents or reduces uremia-related vascular calcification, without overt negative consequences for bone and without calcium pyrophosphate deposition disease. These findings prompt further research into the potential of pyrophosphate as treatment for vascular calcification in chronic kidney disease patients.

Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats.

Objective: To investigate cell biological changes in calcified aortas of rats that experienced chronic renal failure.

Methods And Results: Vascular smooth muscle cells have the potential to transdifferentiate to either chondrocytes or osteoblasts, depending on the molecular pathways that are stimulated. Uremia-related medial calcification was induced by feeding rats an adenine low-protein diet for 4 weeks.

Prevention and transplantation in chronic kidney disease: what is achievable in emerging countries? Meeting report: Bamako meeting December 4-6, 2008.

Experts from all continents discussed the present and future of nephrology and transplantation medicine in emerging countries during a 3-day conference, supported by the World Health Organization, the International Society of Nephrology, the Transplantation Society-Global Alliance for Transplantation and the Ministry of Health of the Republic of Mali. This conference was held in Bamako, Mali on December 4-6, 2008, and focused on prevention and treatment of chronic kidney disease in emerging countries. Apart from delivering high-quality medical and scientific knowledge, the meeting was mainly a call to action for emerging countries to start chronic kidney disease prevention and screening programs, develop end-stage renal disease registries and start or further elaborate transplantation programs.

Vascular calcification and bone disease: the calcification paradox.

Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Remarkably, ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover. This contradictory association, observed mainly in osteoporosis and chronic kidney disease, is called the 'calcification paradox'.

Possibilities and limits of X-ray microtomography for in vivo and ex vivo detection of vascular calcifications.

In the present paper, vascular calcifications due to chronic renal failure in rats are studied by X-ray microtomography (micro-CT). Although micro-CT is traditionally used as an imaging technique, a quantitative analysis of data obtained by in vivo and ex vivo micro-CT is described and discussed. By comparison with traditional destructive methods, such as histomorphometry and atomic absorption, the detection limits for calcium were determined in living rats and in extracted aortas.

[Experimental study of the mechanism for vascular calcification in chronic kidney disease].

Vascular calcification or ectopic calcification ofblood vessels forms an important element of the increased cardiovascular risk observed in patients with chronic kidney disease. In addition to the classical Framingham risk factors, specific uremia-related factors such as hyperphosphatemia and disturbed calcium and phosphorus metabolism contribute to the development of vascular calcification. To gain a better insight into the mechanism of this calcification process, experimental techniques were developed to induce and detect vascular calcification in rats with in vivo micro-CT imaging.

Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats.

Background: Hyperphosphataemia is a risk factor for arterial calcification contributing to the high cardiovascular mortality in patients with chronic kidney disease. Calcium-based phosphate binders can induce hypercalcaemia and are associated with progression of vascular calcification. Therefore, the effect of lanthanum carbonate, a non-calcium phosphate binder, on the development of vascular calcification was investigated in uraemic rats.

Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate.

Elevated serum phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperphosphatemia, and in general treatment with oral phosphate binding agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients.

Balanced calcitriol treatment to make children grow.

Short stature is an important clinical problem in children with chronic kidney disease. Calcitriol is used as standard therapy to control secondary hyperparathyroidism, but its effect on linear growth remains controversial. Sanchez and He report multiple effects of calcitriol on chondrocyte proliferation and maturation that might help to clarify this controversy.

Endochondral bone formation is involved in media calcification in rats and in men.

Arterial media calcification is often considered a cell-regulated process resembling intramembranous bone formation, implying a conversion of vascular tissue into a bone-like structure without a cartilage intermediate. In this study, we examined the association of chondrocyte-specific marker expression with media calcification in arterial samples derived from rats with chronic renal failure (CRF) and from human transplant donors. CRF was induced in rats with a diet supplemented with adenine.

Uremia-related vascular calcification: more than apatite deposition.

In the present study, we characterized and compared the mineral phase deposited in the aortic wall of two different frequently used chronic renal failure rat models of vascular calcification. Vascular calcification was induced in rats by either a 4-week adenine treatment followed by a 10-week high-phosphate diet or 5/6 nephrectomy followed by 6 weeks of 0.25 microg/kg/day calcitriol treatment and a high-phosphate diet.

Bisphosphonates prevent experimental vascular calcification: Treat the bone to cure the vessels?

Bisphosphonates are inhibitors of bone resorption that are widely used to treat osteoporosis. Price and colleagues demonstrate that ibandronate suppressed the development of uremia-related vascular calcification in rats. These findings extend the link between bone remodeling and vascular calcification to the context of chronic renal failure, opening perspectives toward novel therapeutic strategies.

High-resolution X-ray microtomography is a sensitive method to detect vascular calcification in living rats with chronic renal failure.

Objective: Chronic renal failure (CRF) is associated with a 10- to 20-fold increase in cardiovascular risk. Vascular calcification is a prominent feature of cardiovascular disease in patients with end-stage renal failure and contributes to the excess mortality in this population. In this study, we explored in vivo X-ray microtomography (micro-CT) as a tool to detect and follow-up vascular calcifications in the aorta of living rats with adenine-induced CRF.

Lanthanum: a safe phosphate binder.

Accumulation of inorganic phosphate due to renal functional impairment contributes to the increased cardiovascular mortality observed in dialysis patients. Phosphate plays a causative role in the development of vascular calcification in renal failure; treatment with calcium-based phosphate binders and vitamin D can further increase the Ca x PO(4) product and add to the risk of ectopic mineralization. The new generation of calcium-free phosphate binders, sevelamer and lanthanum, can control hyperphosphatemia without adding to the patients calcium load.

Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia-reperfusion.

Introduction: Beside lung transplantation, cardiopulmonary bypass, isolated lung perfusion and sleeve resection result in serious pulmonary ischemia-reperfusion injury, clinically known as acute respiratory distress syndrome. Very little is known about cells infiltrating the lung during ischemia-reperfusion. Therefore, a model of warm ischemia-reperfusion injury was applied to differentiate cellular infiltrates and to quantify tissue damage.

T cells as mediators in renal ischemia/reperfusion injury.

Inflammation has been established to contribute substantially to the pathogenesis of ischemia/reperfusion (I/R) with a central role for particular cells, adhesion molecules, and cytokines. Until recently, most of the research trying to unravel the pathogenesis of I/R injury has been focused on the role of neutrophils. However, recent studies have brought evidence that T cells and macrophages are also important leukocyte mediators of renal and extrarenal (liver) I/R injury.

ICAM-1 expression and leukocyte accumulation in inner stripe of outer medulla in early phase of ischemic compared to HgCl2-induced ARF.

Background: After ischemia/reperfusion (I/R), as well as after toxic insults, there is significant infiltration of leukocytes in the kidney. It is well known that antibodies against adhesion molecules [e.g.

Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice.

Background: Osteopontin (OPN) is a phosphoprotein that is up-regulated in several experimental models of renal disease, including ischemia/reperfusion injury. OPN has been described as a macrophage chemoattractant, may serve as a survival factor for tubular cells, and is implicated in the development of tubulointerstitial fibrosis. However, the precise role of this protein in renal pathophysiology remains unclear.

Crystal retention capacity of cells in the human nephron: involvement of CD44 and its ligands hyaluronic acid and osteopontin in the transition of a crystal binding- into a nonadherent epithelium.

Nephrolithiasis requires formation of crystals followed by their retention and accumulation in the kidney. Crystal retention can be caused by the association of crystals with the epithelial cells lining the renal tubules. The present study investigated the interaction between calcium oxalate monohydrate (COM) crystals and primary cultures of human proximal (PTC) and distal tubular/collecting duct cells (DTC).

Osteopontin synthesis and localization along the human nephron.

In normal human and rat kidneys, osteopontin (OPN) is present at the apical surface of cells in the distal nephron. After ischemic or toxic renal damage in rats, OPN is upregulated in distal tubular cells (DTC) and expressed de novo in perinuclear vesicles in proximal tubular cells (PTC). In the first phase of this study, OPN localization in ischemic human biopsies was compared with that in ischemic rat kidneys.

Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia.

Background: Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both B7-1 and B7-2 costimulatory molecules, protects the kidney during acute ischemia/reperfusion injury. This study investigated whether and how B7-1 and/or B7-2 proteins are involved in renal ischemia/reperfusion injury (IRI).

Methods: Uninephrectomized rats were submitted to warm renal ischemia (30 min) and received control monoclonal antibody (mAb; 17E3), anti-B7-1 (3H5), anti-B7-2 (24F), a combination of anti-B7-1/B7-2, or CTLA-4 Ig.

Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat.

Background: The effect of segment-specific proximal tubular injury on spatio-temporal osteopontin (OPN) distribution was determined in two different nephrotoxic rat models to evaluate its conceivability with a possible role for OPN in acute renal failure (ARF). OPN gene expression was further determined in proximal and distal tubular cells to investigate the origin of increased renal OPN.

Methods: Renal OPN protein and mRNA expression were compared in the rat during mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and in situ hybridization.