[Lipid profile of patients on chronic hemodialysis (Morocco)]. / Profil lipidique dans l'insuffisance rénale chronique au stade d'hémodialyse : étude marocaine.

INTRODUCTION: Patients with end-stage renal disease (ESRD) receiving chronic hemodialysis show a high incidence and prevalence of cardiovascular disease of multifactorial etiology and an association between dyslipidemia and accelerated atherosclerosis. OBJECTIVE: Our aim was to study lipid profiles in ESRD patients receiving dialysis regularly at our hospital (Morocco).Subjects and methods : The patient population consisted of 30 ESRD patients on maintenance haemodialysis. Matched control subjects were recruited among healthy normolipidemic patients. Concentrations of triglycerides (TG), total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C) were measured. The atherogenic index (AI = TC/HDL-C ratio) was calculated. RESULTS: The TG, the HDL-C levels and atherogenic index were significantly higher in groups of hemodialysis patients. We saw no increase in the levels of TC and LDL-C. The prevalence of dyslipidemia in hemodialysis group was high (80%). The most frequent lipid alterations were decreased HDL-C (70%), increased TG (33,3%) and increased LDL-C (23,3%); 50% of ESRD patients have more than two different dyslipidemic findings. AI was higher (≥ 5) in 33,3% of cases. CONCLUSION: The prevalence of dyslipidemia is higher than normal in ESRD patients on maintenance hemodialysis. Classically, these patients have had low levels of HDL-C and elevated TG levels. Strict control of dyslipidemia should be part of the cardiovascular risk prevention strategy in this population.

Effects of antisense oligodeoxynucleotides targeting CCR3 on the airway response to antigen in rats.

Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation, consisting predominantly of eosinophils within the airway lumen and walls. Eosinophil recruitment to the airways is mediated mainly by eotaxin and other chemokines that bind to the CC-chemokine receptor-3 (CCR3), which is highly expressed on eosinophils. This study assessed whether topical inhibition of CCR3 mRNA expression by phosphorothioate antisense oligodeoxynucleotides (AS-ODNs) modifies pulmonary eosinophilia and AHR in an antigen-induced allergic asthma model in Brown Norway (BN) rats. Results show that specific inhibition of CCR3 expression in the lungs by an AS-ODN (AS4) reduced total eosinophil infiltration and the percentage of eosinophils into the airways of ovalbumin challenged rats. Moreover, reduction in CCR3 mRNA levels was correlated with a decrease in CCR3 protein in lung tissue. In addition, AS4 treatment had no effect on circulating eosinophils or on eosinophils in the bone marrow. Finally, AHR was significantly decreased in AS4-treated rats when compared with rats treated with a mismatch AS-ODN. In conclusion, inhibition of the expression of CCR3 decreased pulmonary eosinophilia and reduced AHR after antigen challenge in rats. Topical inhibition of CCR3 expression, using an AS-ODN, could represent a novel approach for the treatment of asthma.

[Acute renal failure as a complication of Mediterranean spotted fever]. / Fièvre boutonneuse méditerranéenne compliquée d'insuffisance rénale aiguë.

The Mediterranean spotted fever is a bacterial infection caused by Rickettsia Conorii mainly around Mediterranean basin. It is often considered like a trivial infection. However, severe forms with a high morbidity and high mortality risk have been described. These forms often associate with impaired consciousness, abnormal liver function, impaired homeostasis, pneumonia and acute renal failure. Several mechanisms of renal damage during the Mediterranean spotted fever have been reported, their pathogenesis remains speculative and the prognosis is determined by the type of renal disease and on early treatment. Thus, rickettsiosis should be considered in combination of acute renal, hepatic cytolysis and thrombocytopenia, allowing rapid achievement of a specific treatment.

Infective endocarditis in chronic hemodialysis patients: experience from Morocco.

Since the 1960s, regular hemodialysis (HD) was recognized as a risk factor for the development of infective endocarditis (IE), particularly at vascular access sites. The present report describes our experience at the Etat Major General Agadir, Morocco, of taking care of IE in patients on regular dialysis. A retrospective analysis was made of five cases of IE in patients receiving regular HD having arteriovenous fistula as vascular access. They were sent from four private centers and admitted in our formation between January 2004 and March 2009. Infective endocarditis was detected after 34.5 months following initiation of dialysis. The causative organisms included Staphylococcus and Enterococcus in two cases each and negative blood culture in one case. A recent history of infection (<3 months) of the vascular access was found in three cases. Peripheric embolic phenomena were noted in two cases. A pre-existing heart disease was common and contributed to heart failure. Mortality was frequent due to valvular perforations and congestive heart failure, making the medical treatment alone unsatisfactory. Two patients survived and three of our patients received a prosthetic valve replacement, with a median survival after surgery of 10.3 months/person. The clinical diagnosis of infective endocarditis in regularly dialyzed patients remains difficult, with the presence of vascular calcification as a common risk factor. The vascular catheter infections are the cardinal gateway of pathogenic organisms, which are mainly Staphylococcus. The prognosis is bad and the mortality is significant, whereas medical and surgical treatments are often established in these patients who have many factors of comorbidity.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism]. / Insuffisance rénale aiguë révélant une hypothyroïdie auto-immune.

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders.

Enhancement of Th1 type cytokine production and primary T cell activation by PBI-1393.

In previous reports, we have shown that PBI-1393 (formerly BCH-1393), N,N-Dimethylaminopurine pentoxycarbonyl D-arginine, stimulates cytotoxic T-lymphocyte (CTL) responses both in vitro and in vivo in normal immune status and immunosuppressed mice. Additionally, PBI-1393 was tested for anticancer activity in syngeneic mouse experimental tumor models and it displayed significant inhibition of tumor outgrowths when given in combination with sub-therapeutic doses of cytotoxic drugs (cyclophosphamide, 5-fluorouracil, doxorubicin and cis-platinum). However, the mechanism of action of PBI-1393 was still unknown. Here, we report that PBI-1393 enhances IL-2 and IFN-gamma production in human activated T cells by 51% and 46% respectively. PBI-1393 increases also IL-2 and IFN-gamma mRNA expression as shown by RT-PCR. The physiological relevance of IL-2 and IFN-gamma gene modulation by PBI-1393 is illustrated by the advantageous increase of T cell proliferation (39+/-0.3% above control) and human CTL response against prostate (PC-3) cancer cells (42+/-0.03%). The enhancement of human T cell proliferation and CTL activation by PBI-1393 demonstrates that this compound potentiates the immune response and in this regard, it could be used as an alternative approach to IL-2 and/or IFN-gamma therapy against cancer.

Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma.

Airway obstruction, hyperresponsiveness, and the accumulation and persistence within the airways of inflammatory cells characterize asthma. Interleukin (IL)-3, granulocyte macrophage colony- stimulating factor (GM-CSF), and IL-5 are among several cytokines that have been shown to be increased in asthma and to contribute to atopic inflammation. They mediate their effect via receptors that have a common beta subunit (beta(c)). We hypothesized that blocking of this common beta(c) would impair the airway response to antigen. We report that an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) found to specifically inhibit transcription of the beta(c) in rat bone marrow cells also caused inhibition of beta(c) mRNA expression and of immunoreactive cells within the lungs of Brown Norway (BN) rats when injected intratracheally (p < 0.01). Inhibition of beta(c) significantly reduced (p < 0.01) experimentally induced eosinophilia in vivo in ovalbumin (OVA)-sensitized BN rats after antigen challenge. Furthermore, when compared with mismatch-treated rats, beta(c) AS-ODN caused inhibition of antigen-induced airway hyperresponsiveness to leukotriene D4. Taken together, our findings demonstrate that the common beta(c) of IL-3, IL-5, and GM-CSF receptors is involved in the eosinophil influx and airway hyperresponsiveness that follow OVA challenge and underscore the potential utility of a topical antisense approach targeting beta(c) for the treatment of asthma.