Metabolic profiling of human plasma and urine in chronic kidney disease by hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry: a pilot study.

A typical characteristic of chronic kidney disease (CKD) is the progressive loss in renal function over a period of months or years with the concomitant accumulation of uremic retention solutes in the body. Known biomarkers for the kidney deterioration, such as serum creatinine or urinary albumin, do not allow effective early detection of CKD, which is essential towards disease management. In this work, a hydrophilic interaction liquid chromatography time-of-flight mass spectrometric (HILIC-TOF MS) platform was optimized allowing the search for novel uremic retention solutes and/or biomarkers of CKD.

Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, and its structural isomer symmetric dimethylarginine (SDMA) are uremic toxins accumulating in chronic kidney disease (CKD) patients. The objective of this study was to develop and validate a robust UPLC-MS/MS method for the simultaneous determination of ADMA and SDMA in human serum. Chromatographic separation after butyl ester derivatization was achieved on an Acquity UPLC BEH C18 column, followed by tandem mass spectrometric detection.

New methods and technologies for measuring uremic toxins and quantifying dialysis adequacy.

This publication reviews the currently available methods to identify uremic retention solutes, to determine their biological relevance and to quantify their removal. The analytical methods for the detection of uremic solutes have improved continuously, allowing the identification of several previously unknown solutes. Progress has been accelerated by the development of comprehensive strategies such as genomics, proteomics and the latest "omics" area, metabolomics.

Uremia-related oxidative stress in leukocytes is not triggered by β2-microglobulin.

Background: Chronic kidney disease (CKD) is characterized by low-grade inflammation and increased risk for cardiovascular disease. The interest in β2-microglobulin (B2M) as a marker for cardiovascular outcome with and without CKD has grown. Clinical studies suggested that B2M could be involved in the pathogenesis of vascular disease, for which chronic leukocyte activation is a pathogenic factor.

A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients.

Chronic kidney disease (CKD) is a devastating illness characterized by accumulation of uremic retention solutes in the body. The objective of this study was to develop and validate a simple, rapid, and robust UPLC-MS-MS method for simultaneous determination, in serum, of seven organic acid uremic retention toxins, namely uric acid (UA), hippuric acid (HA), indoxylsulfate (IS), p-cresylglucuronide (pCG), p-cresylsulfate (pCS), indole-3-acetic acid (IAA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). Isotopically labeled internal standards (d(5)-HA; 1,3-(15)N(2)-UA, and d(5)-IAA) were used to correct for variations in sample preparation and system performance.

Association of haptoglobin phenotypes with the development of Kaposi's sarcoma in HIV patients.

Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive patients.

Circulating cytokines in pulmonary tuberculosis according to HIV status and dietary iron content.

Objective: To evaluate human immunodeficiency virus (HIV) serology, dietary iron and serum concentrations of markers of T-helper type (Th) 1 and Th-2 immune pathways in the setting of tuberculosis (TB).

Methods: A total of 49 patients with pulmonary TB in rural Zimbabwe, 32 of whom were HIV-positive, were evaluated at presentation and over 10 weeks of anti-tuberculosis treatment.

Results: Interleukin (IL) 12 and neopterin, Th-1 markers, were both elevated at presentation in 92% of the subjects.

Staphylococcus aureus infections in hemodialysis: what a nephrologist should know.

Staphylococcus aureus is a formidable pathogen that has the ability to colonize approximately half the dialysis population without any sign of disease but is also capable of causing wound and tissue infections; fulminant septicemia; and chronic, difficult-to-eradicate and often foreign body-related infections. S. aureus is the main cause of infectious morbidity and mortality in hemodialysis patients.

The effect of the host's iron status on tuberculosis.

Several lines of evidence have suggested that iron is critical for Mycobacterium tuberculosis growth in macrophages. Macrophage iron loading in patients with African iron overload increases the risk of tuberculosis (TB) and may worsen TB outcome. Likewise, macrophage iron loading may contribute to an increased predisposition toward TB in HIV infection.

The prevention of the growth of Leishmania major progeny in BALB/c iron-loaded mice: a process coupled to increased oxidative burst, the amplitude and duration of which depend on initial parasite developmental stage and dose.

BALB/c mice were given or not iron around the time of intradermal parasite inoculation, in their ears, of either 10(6) stationary-phase (designated "high-dose model") or 10(3)Leishmania major metacyclic promastigotes (designated "low-dose model"). Iron-loaded mice in the high-dose model displayed delayed and limited pathogenic processes, whereas in the low-dose model, the mice remained ear lesion-free over 12 months post-parasite inoculation. These phenotypes were coupled to an increased leukocyte oxidative burst displayed mainly by neutrophils: it was early and transient in the high-dose model, whereas it was sustained in the low-dose model.

Linezolid-induced inhibition of mitochondrial protein synthesis.

Background: Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled.

Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature.

Therapy of systemic lupus erythematosus (SLE) with major organ involvement consists of aggressive immunosuppression with glucocorticoids and cytotoxic agents. When remission is achieved, maintenance therapy is begun to reduce the risk of relapse while minimizing toxicity. Remission with standard therapy is, however, not always achieved.

Prohepcidin accumulates in renal insufficiency.

Background: The understanding of iron metabolism has increased substantially during the last decade. Several new transporters and iron regulating molecules have been described. Hepcidin, a small hepatic peptide has recently been proposed as a central mediator of dietary iron absorption.

Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors.

Objective: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1).

Design: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions.

Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients.

Background: Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required.

Effects of chloroquine on viral infections: an old drug against today's diseases?

Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses.

Tuberculosis of the skull: a case report.

Tuberculosis of the skull is rare. We describe a case of skull tuberculosis in a Somali fugitive. The patient presented with a history of a painful mass at the vertex of the skull.

Iron withdrawal strategies fail to prevent the growth of SiHa-induced tumors in mice.

Objective: Cervical carcinoma is a human papillomavirus (HPV)-associated cancer for which treatment options still mainly rely on surgical procedures, with or without adjuvant radiotherapy and chemotherapy. We have previously shown that the chemically unrelated iron chelators desferrioxamine and deferiprone inhibit the growth and induce the apoptosis of HPV-positive cervical carcinoma cell lines, suggesting that iron chelators may represent a potential therapeutic approach for the treatment of cervical carcinoma. The present study was designed to investigate the effect of iron deprivation on the growth of human cervical carcinoma xenografts in athymic nude mice.

Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis.

The authors report on a premenopausal female hemodialysis patient with relapsing pneumothorax, in whom the diagnosis of pulmonary lymphangioleiomyomatosis (LAM) was made. Ten years earlier, she had retroperitoneal bleeding from a kidney tumor corresponding to an angiomyolipoma (AML). The association between renal AML and pulmonary LAM is reviewed.

Differential cytokine pattern in the spleens and livers of BALB/c mice infected with Penicillium marneffei: protective role of gamma interferon.

Penicillium marneffei is an intracellular opportunistic fungus causing invasive mycosis in AIDS patients. T cells and macrophages are important for protection in vivo. However, the role of T-cell cytokines in the immune response against P.

Prevention of Staphylococcus aureus biofilm on dialysis catheters and adherence to human cells.

Background: Dialysis patients, often carriers of Staphylococcus aureus in their nares, are at high risk of S. aureus infections.

Methods: We examined whether RNAIII inhibiting peptide (RIP), which interferes with quorum sensing mechanisms, reduces adherence of S.

Iron overload exacerbates experimental meningoencephalitis by Cryptococcus neoformans.

This study was aimed at investigating the effects of iron overload on the onset and outcome of cerebral cryptococcosis. To this purpose, iron dextran-administered mice were intracerebrally challenged with virulent melanogenic and avirulent non-melanogenic strains of Cryptococcus neoformans. The results shown here provide the first evidence that iron overload exacerbates the outcome of cryptococcal meningoencephalitis, irrespective of the fungal strain employed; pathogen colonization of the brain is facilitated, local cytokine response is delayed and/or prevented.