Raymond Farah

Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment

IntroductionThe metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems. Endothelial injury is induced by oxidative stress (OS) and inflammation. We have previously shown that DM type 2 patients are exposed to increased OS and inflammation contributed in part by primed peripheral polymorphonuclear leukocytes (PMNLs).AimsTo characterize the effect of oral medication on PMNL priming, on PMNL-related and on systemic inflammation, in correlation to changed diabetes parameters in patient with newly diagnosed type 2 DM.MethodsPMNLs were separated from DM patients prior and following treatment with either metformin (Glucophage), or Thiazolidinedione (rosiglitazone) and from healthy control subjects (HC). Rate of superoxide release from phorbol ester-stimulated PMNLs and CD11b on PMNLs assessed PMNL priming. White blood cells (WBC) and PMNL counts and apoptosis reflected PMNL-related inflammation. CRP, fibrinogen, transferrin and albumin blood levels reflected systemic inflammation.ResultsBoth metformin and rosiglitazone treatments reduced significantly the high levels of glucose and HbA1c, and slightly improved lipid profile during 2 months. PMNL priming parameters, higher compared to HC, increased after 2 months of metformin treatment. Rosiglitazone treatment decreased PMNL priming. ALP, higher in DM, significantly decreased following 2 months of both treatments. Systemic inflammation markers (fibrinogen, CRP), higher in DM, decreased following both treatments. Transferrin and albumin were similar to HC. PMNL-related inflammation markers were higher in DM; however, only PMNL apoptosis decreased after both treatments. Monocyte counts, higher in DM compared to HC, decreased following both treatments. Serum insulin levels, higher in DM compared to HC, decreased following both treatments. PMNL-related priming and inflammation parameters positively correlated with HbA1c.ConclusionThe present research adds new facet in evaluating anti-hyperglycemic treatment in type 2 DM patients. Despite sufficient glycemic control using both treatments, some PMNL-related parameters deteriorated. Thus, anti hyperglycemic treatment should be favored due to its combined anti-PMNL priming and anti-inflammatory effect, in addition to its anti-hyperglycemic characteristics, according to the correlation among these parameters. Such combined treatment may reduce morbidity and mortality common in DM patients.

A link between polymorphonuclear leukocyte intracellular calcium, plasma insulin, and essential hypertension

BACKGROUND Intracellular ionized calcium ([Ca2+]i) is a key mediator in the activation and oxidant production by peripheral polymorphonuclear leukocytes (PMN). Primed PMN contribute to oxidative stress (OS) and inflammation in essential hypertension (EH). Elevated [Ca2+]i has been described in insulin-resistant states and in various cell types in EH but not in EH PMN. The aim of this study was to evaluate the levels of [Ca2+]i in peripheral EH PMN in relation to plasma insulin levels and blood pressure (BP). METHODS The PMN were separated from blood of 20 nonsmoking, nonobese untreated EH patients, age range 20 to 60 years and from 20 age- and gender-matched healthy individuals (NC). Plasma glucose and insulin levels 2 h after a 75-g oral glucose load, reflected insulin resistance. PMN [Ca2+]i was measured by flow cytometry in isolated cells stained with Fluo-3. RESULTS The EH PMNs showed significantly increased [Ca2+]i compared to NC PMN. Eighty percent of EH patients showed significantly higher plasma insulin levels after glucose load. Linear regression analysis showed significant correlation between 1) PMN [Ca2+]i and mean arterial pressure (MAP) (r = 0.5, P < .006); 2) PMN [Ca2+]i and fasting plasma insulin (r = 0.7, P < .005); and 3) fasting plasma insulin and MAP (r = 0.4, P < .04). CONCLUSIONS This study adds PMN to previously described cells exhibiting elevated [Ca2+]i, contributing to OS and inflammation. The correlation of individual BP with both PMN [Ca2+]i and plasma insulin levels, together with the fact that elevated [Ca2+]i mediates PMN priming, suggest that elevated [Ca2+]i and insulin are involved in the pathogenesis of hypertension-induced vascular injury in EH.

Limited Wegener’s granulomatosis—is it limited?

Complete heart block associated with Wegener’s granulomatosis (WG) is rare especially in the limited form of the disease. We describe a case of a 43-year-old woman with a limited form of WG who developed a complete heart block. Prompt treatment with steroids and cyclophosphamide led to temporary regression of complete heart block. Further involvement of lung was treated successfully by tumor necrosis factor-alpha inhibitor infliximab. Cardiac rhythm abnormalities should always be kept in mind both in diagnosis and follow-up of WG.

Amanita phalloides causing acute renal failure and liver disease resolved with intensive therapy

In this unusual case we report the history of two persons who were hospitalized after the ingestion of wild mushrooms identified as Amanita Phalloides. The two individuals developed severe symptoms until acute renal failure and liver injury resolved completely due to the rapid diagnosis and the intensive immediate treatment within 24 hours using new methods including hemodialysis and Molecular Adsorbent Recycling System (MARS).