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Biomedical subjects

Hassane Izzedine

Publications and source records attributed to Hassane Izzedine.

At least 19 recordsLinked to original sources

Sunitinib malate.

Recently, there has been a growing interest in understanding the role of receptor tyrosine kinases (RTK), such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (KIT), and fms-like tyrosine kinase 3 (FLT3), in promoting tumor angiogenesis, tumor growth and metastasis. Sunitinib (sunitinib malate; SU11248; SUTENT; Pfizer Inc, New York, NY, USA) is a novel, orally bio-available, oxindole, multi-targeted tyrosine kinase inhibitor with high binding affinity for VEGFR and PDGFR which has shown anti-tumor and anti-angiogenic activities. This drug recently received approval from the US Food and Administration (FDA) in two indications simultaneously: advanced renal cell carcinoma (adRCC) and gastrointestinal stromal tumors (GIST), in patients who are resistant or intolerant to the treatment with imatinib. The present article reviews the recent pharmacologic and clinical data related to the use of this new promising drug in the field of oncology.

Antineoplastic Agents↗

Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) may induce renal proximal tubulopathy (rPT). There are no data on pharmacogenomic predictors of rPT in the genes encoding the multidrug-resistance protein (MRP) 2 and MRP4 transporters. METHODS: Mutational screening of the genes for MRP2 (ABCC2) and MRP4 (ABCC4) was performed using genomic DNA from 13 human immunodeficiency virus type 1 (HIV-1)-infected patients (group 1) presenting with TDF-induced rPT. Concomitantly, 17 unrelated HIV-1-infected patients who had received TDF therapy and who did not have rPT (group 2) were included in a case-control analysis, to assess the influence of single-nucleotide polymorphisms (SNPs) identified in ABCC2 and ABCC4. RESULTS: Six SNPs were identified in ABCC2. A significant allelic association between the 1249 G-->A SNP and TDF-induced rPT was observed (odds ratio, 6.11 [95% confidence interval, 1.19-31.15]; P<.02). ABCC2 haplotypes were significantly associated with the onset of TDF-induced rPT--CATC appeared to be a predisposing haplotype, as it was found in 40.9% of the group 1 case patients and in 13.7% of the group 2 control subjects (P<.01), whereas CGAC appeared to be a protective haplotype, as it was not observed in the group 1 case patients but was present in 20.2% of the group 2 control subjects (P<.01). No association was observed between ABCC4 polymorphism and TDF-induced rPT in the present study. CONCLUSION: ABCC2 haplotypes are associated with rPT induced by TDF in HIV-1-infected patients.

Adenine↗

[Drud-induced nephrotoxicity: Bibliography from January 2003 to December 2005].

Drug-induced kidney injury is a major side effect in clinical practice. Renal injury associated with drugs may involve several components of the kidney: glomerulus, tubules, interstitium, and blood vessels. Acute renal failure may occur as a major reaction to many drugs. Moreover, therapeutic agents may induce an allergic reaction leading to interstitial inflammation and tubular damage. In this article, we present an updated version of the bibliography containing the case reports of nephrotoxicity published in the international literature from January 2003 to December 2005.

Humans↗

Renal tubular drug transporters.

The kidney plays an important role in the elimination of numerous hydrophilic xenobiotics, including drugs, toxins, and endogenous compounds. It has developed high-capacity transport systems to prevent urinary loss of filtered nutrients, as well as electrolytes, and simultaneously to facilitate tubular secretion of a wide range of organic ions. Transport systems for organic anions and cations are primarily involved in the secretion of drugs in renal tubules. The identification and characterization of organic anion and cation transporters have been progressing at the molecular level. To date, many members of the organic anion transporter, organic cation transporter, and organic anion-transporting polypeptide families have been found to mediate the transport of diverse organic ions. It has also been suggested that ATP-dependent primary active transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein family function as efflux pumps of renal tubular cells for more hydrophobic molecules and anionic conjugates. Tubular reabsorption of peptide-like drugs such as beta-lactam antibiotics across the brush-border membranes appears to be mediated by two distinct H+/peptide cotransporters: PEPT1 and PEPT2. Renal disposition of drugs occurs through interaction with these diverse secretory and absorptive transporters in renal tubules. Studies of the functional characteristics, such as substrate specificity and transport mechanisms, and of the localization of drug transporters could provide information regarding the cellular network involved in renal handling of drugs. Detailed information concerning molecular and cellular aspects of drug transporters expressed in the kidney has facilitated studies of the mechanisms underlying renal disposition as well as transporter-mediated drug interactions.

Animals↗

Abnormal blood pressure circadian rhythm: a target organ damage?

Blood pressure (BP) varies according to cycles characterized by a reduction during sleep and an increase on awakening. The nighttime decrease is absent or blunted in some patients (termed "non-dippers"). Cross-sectional and prospective data have shown that non-dippers have more target organ damage than have dippers in normotensive and hypertensive subjects. We reviewed the English language literature regarding this association. A non-fortuitous association seems to exist between non-dipper status and cardiovascular risk such as stroke and cardiac events. Among diabetic patients, this phenomenon has been described to occur more often in individuals with autonomic neuropathy and with different degrees of diabetic nephropathy. In normoalbuminuric normotensive type I diabetic patients without any degree of autonomic dysfunction, according to traditional cardiovascular tests, diastolic BP (dBP) night/day ratio is associated with an increased glomerular filtration rate and an increased extracellular volume. The disruption of the circadian rhythm of sympathovagal activity in non-dipper patients was associated with higher levels in systolic BP (sBP) and dBP and with a reduced decline in sBP and dBP levels during the night. Therefore, the prognostic implications of the non-dipper status may be important since the overall 24-h blood pressure load is elevated in these individuals. These data suggest that patients in whom blood pressure decreases during the night incur less damage to their brain, kidneys, heart, and blood vessels than people with elevated nocturnal BP.

Antihypertensive Agents↗

Oculo-renal disorders in infectious diseases.

BACKGROUND: The aim of this article is to review the potential ocular and renal disorders in infectious diseases to which humans are susceptible and to determine prevalence of these diseases. METHODS: Published cases of oculo-renal disorders associated with various infectious diseases were collected from the international literature by searching the MEDLINE database (PUBMED 1970-2004) for original reports and review articles published in English. Citations from papers retrieved were screened and retrieved papers were evaluated. RESULTS: Based on the screened data, we propose a practical, structure-oriented checklist of such lesions divided into bacterial, viral, parasital, and fugal infections. CONCLUSION: The oculorenal manifestations of infectious diseases may be flagrant or subtle. Awareness of the signs and symptoms of infections allows early recognition and prompt, appropriate management. The clinical presentation and relative frequency of those manifestations are reviewed.

Anti-Bacterial Agents↗

Loss of podocyte dysferlin expression is associated with minimal change nephropathy.

We report a case of limb-girdle muscular dystrophy type 2B (LGMD2B) associated with minimal change disease. Immunohistochemical examination of quadriceps muscle showed a deficiency in dysferlin in sarcolemma, and dysferlin gene analysis showed 3370 G missense mutation, leading us to the diagnosis of LGMD2B. The patient also developed glomerular proteinuria. We also explored urinary protein levels in 3 other patients with dysferlinopathy and found microalbuminuria with albumin excretion of 0.14 to 0.18 g/d in 2 patients. Renal abnormalities during LGMD2B and kidney dysferlin expression have never been reported. Renal biopsy showed a lack of glomerular dysferlin expression compared with a positive immunohistochemical marking in patients with idiopathic minimal change nephropathy and healthy controls. We therefore suggest that dysferlin is present in glomeruli and may be associated with glomerular permeability.

Adult↗

[Drug-induced nephrotoxicity: bibliography from January 2003 to December 2004].

Drug-induced kidney injury is a major side effect in clinical practice. Renal injury associated with drugs may involve several components of the kidney: glomerulus, tubules, interstitium and blood vessels. Acute renal failure may occur as a major reaction to many drugs. Moreover, therapeutic agents may induce an allergic reaction leading to interstitial inflammation and tubular damage. In this article, we present an updated version of the bibliography containing the case reports of nephrotoxicity published in the international literature from January 2003 to December 2004.

Drug-Related Side Effects and Adverse Reactions↗