Hypertension and nephrology

[Changes in endothelial cells caused by cigarette smoke]

WAGNER László1, LACZY Boglárka1, CSEH Judit1, TAMASKÓ Mónika1, MAZÁK István1, MARKÓ Lajos1, MOLNÁR Gergő Attila1, WAGNER Zoltán1, MOHÁS Márton1, FEKETE Andrea2, WITTMANN István1

JUNE 20, 2010

Hypertension and nephrology - 2010;14(03)

[Endothelial nitric oxide synthase enzyme is regulated through the phosphorylation of the Ser(1177) and the Thr(495) sites, which influence the biological availabilaty of nitric oxide. We examined the acute effect of cigarette smoke, which decreases nitric oxide production. Endothelial cells were treated with different concentrations and for different times with cigarette smoke buffer, then with reduced glutathione or different protein kinase inhibitors. We determined the total and the phosphorylated nitric oxide synthase levels with Western blot. Cigarette smoke increased phosphorylation in a concentration- and time dependent manner at the Ser(1177) site and more pronounced at the Thr(495) site. Besides, it also led to the dissociation of the active dimer form of the enzyme. Reduced glutathione inhibited these phosphorylations and prevented the dissociation of endothelial nitric oxide synthase enzyme. The inhibition of protein kinase A or B did not influence the effect of cigarette smoke. However, protein kinase C inhibitors increased the phosphorylation caused by cigarette smoke at Ser(1177), but decreased it at Thr(495) sites. Summarized, cigarette smoke shifts the phosphorylation of the enzyme towards an inhibitory state, further on, it leads to the dissociation of the enzymatically active form. This results in the decreased biological availabilaty of nitric oxide, in which protein kinase C may play an important role.]

AFFILIATIONS

  1. Pécsi Tudományegyetem, Általános Orvostudományi Kar, II. Sz. Belgyógyászati Klinika és Nephrológiai Centrum, Pécs
  2. Semmelweis Egyetem, I. Sz. Gyermekgyógyászati Klinika, Budapest

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[Sevelamer: an old-new phosphate binder in chronic kidney disease]

BERECZKI Csaba, TÚRI Sándor

[Sevelamer HCl is a non-metal and non-calcium based phosphate binder, ion exchange resin, which not selectively binds the phosphate ions in the gastrointestinal tract. In Hungary since 2005, on the basis of strict professional guidelines, sevelamer is available therapy for chronic kidney disease patients with severe hyperphosphatemia on dialysis. On the basis of 17 prospective and retrospective studies, sevelamer HCl is an at least as effective phosphate binder as other calcium based binders, in reducing the serum phosphate level. The advantage of sevelamer compared to the other widely used calcium based phosphate binders is the significantly lower serum calcium level and less hypercalcemic episodes. Sevelamer therapy in chronic kidney disease patients reduces the progression of cardiovascular calcification and it has also a positive effect on cholesterol and LDL-cholesterol levels. The side effects of sevelamer therapy may be acidosis, and gastrointestinal complaints. This year the improved form, sevelamer carbonate, becomes available in Hungary. Sevelamer carbonate has similar phosphate and cholesterol binding capacity as that of sevelamer HCl, but it has several advantages: it has a positive effect on acid-base parameters, and may be administered in powder form, which is beneficial for children and for patients with swallowing disorders. The primary analysis of the DCOR study has not revealed any significant difference in the survival and cardiovascular mortality between patient groups treated with calcium based binder or sevelamer. The RIND trial data showed improved survival of new dialysis patients, who were initially treated with sevelamer. Further clinical studies are needed to kaverify the benefits of sevelamer therapy (mortality, cardiovascular calcification) in chronic kidney disease patients. The management of hyperphosphatemia in chronic renal failure is a major challenge even in the first decade of the 21th century. This is the fact, despite that recently three different groups of phosphate binders are available in the clinical practice: the calcium based binders (calcium carbonate, calcium acetate), sevelamer and lanthanum. Which is the best binder? A calcium based or a non-calcium based one? Over the past decade, these issues are in the mainstream of clinical research of nephrology.]

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ZALAI Dóra Márta, SZEIFERT Lilla, NOVÁK Márta

[In this article a practice-oriented narrative review of the depressive disorders in chronic kidney disease is provided. Depressive disorders affect approximately one fourth of the chronic kidney disease population. These mental disorders interfere with physical, cognitive and social functioning and are associated with poor prognosis of patients with chronic kidney disease. Bio-psycho-social factors, including immuno-inflammatory processes, disturbance in glucose- insulin homeostasis, sleep disorders, chronic pain, sexual difficulties, changes in social roles, losses in multiple areas of life and low social support increase the risk for the development of depression. Routine, regular screening of depression in the chronic kidney disease population seems to be warranted. Only limited published evidence is available on the therapeutic possibilities of depression in chronic kidney disease. Preliminary evidence indicates that short, structured psychotherapy may be effective for acute treatment and prevention of psychological distress. Some antidepressants can be applied without the need for dose adjustments. On the other hand, some of the psychotropic medications require dose reduction or should be avoided.]

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