The effect of calcineurin inhibitors on endothelial function in renal transplant recipients

Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end-stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty-four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium-dependent and -independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium-dependent vasodilation was 12.1 +/- 5.1% in group I and it was 6.5 +/- 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 +/- 6.3 and 12.7 +/- 5.6% in groups I and II, respectively. This indicates that the endothelium-dependent and -independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 +/- 39.4 and 43.9 +/- 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post-transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.     

Do Hemodialysis Adequacy Data Reflect Reality?

Hemodialysis (HD) adequacy requires monitoring in line with standards and at appropriate intervals. However, the use of inappropriate or incorrectly applied techniques in the determination of HD adequacy can lead to highly unfortunate results. This study was intended to identify the path to a solution by determining how far HD adequacy in HD centers in our region reflects reality. Three hundred and thirty HD patients from eight centers were included. On the first visit, predialysis and postdialysis blood collection with the centers' own methods being used were observed and errors were recorded. Kt/V1 was calculated from pre‐ and postdialysis blood specimens taken by the units themselves. On the second visit, one session later, pre‐ and postdialysis blood samples were collected in line with guidelines by ourselves, the authors, and Kt/V2 was calculated from these samples. The eight units' total Kt/V2 value was significantly lower compared with Kt/V1 (<0.0001). The level of patients in all centers with Kt/V1 <1.2 was 13.5%, and that of patients with Kt/V2 <1.2 was 22.1%. No center, apart from one unit, managed to complete the collection of blood specimens as recommended by the guidelines. With one exception, blood collection for HD adequacy was not performed using proper technique in any center. This simple but easily overlooked situation, HD being regarded as adequate though in fact it is not, may lead to patients not being treated effectively and accurately and to a rise in mortality and morbidity in the long term.     

Mean platelet volume and β-thromboglobulin levels in familial mediterranean fever: Effect of colchicine use?

BackgroundMany studies have shown that subclinical inflammation persisted during remission period of Familial Mediterranean Fever (FMF) patients but long term effects of subclinical inflammation in these patients aren't clearly known. Besides, a few of the recent studies revealed that risk of atherosclerosis had increased in FMF patients. β-Thromboglobulin (β-TG) is considered as a sensitive marker of platelet activation. In this study Mean Platelet Volume (MPV) and β-TG levels were evaluated in FMF patients.MethodsFollowing the Local Ethics Committee's consent, 25 FMF patients were included in the study. Twenty eight age and sex matched healthy volunteers were recruited as a control group. Lipid profile, inflammatory parameters, hemogram, β-TG, MPV were assessed. Statistical analysis was performed with SPSS for Windows 16.00.ResultsGroup I consisted of 25 FMF cases (16 females, 9 males; mean age: 35.72 ± 12.34 years), Group II consisted of 28 cases (22 females, 6 males; mean age 31.78 ± 10.31 years). There was no statistically significant difference between the groups in terms of age and gender distribution, smoking status, total cholesterol, triglyceride, LDL and MPV (p > 0.05). HDL levels were found to be statistically lower in Group I (p:0.04). Median β-TG levels was significantly higher in Group II than Group I (129.50 (range:372.00) ng/mL versus 104.00 (range:212.80) ng/mL respectively; p:0.03).ConclusionIn this study MPV and β-TG were evaluated for FMF cases and healthy controls, β-TG levels were found significantly lower among patients; we hypothesized that this difference may have resulted from the effect of colchicine use on platelet functions.     

Leukotriene metabolism and proiflammatory cytokines in Crimean Congo hemorrhagic fever

Crimean–Congo hemorrhagic fever (CCHF) is an emerging acute viral infection disease, yet its pathophysiology remains largely uncharacterized. Lipid mediators are molecules that play numerous roles in the physiologic and pathophysiologic conditions in certain viral diseases. No previous study evaluated the status of cysteinyl leukotrienes (CYSLT) and 5-lipoxygenase (5-LO) and their relationship with proinflammatory cytokines in CCHF. A total of 90 subjects including 60 CCHF patients and 30 healthy controls were enrolled the study. Serum CYSLT, 5-LO, interleukin-6 (IL-6), and ferritin levels were determined in the study population. Lower median 5-LO level was determined in patients compared to healthy controls (p = 0.0004). Higher ferritin (p < 0.001) and IL-6 (p < 0.001) levels in patients than healthy controls. No statistically significant difference was observed between patients and controls in terms of CYSLT levels. No statistically significant differences were observed between mild, moderate, and severe groups in terms of both 5-LO and CYSLT levels. IL-6 and ferritin levels were higher in severe group compared mild and moderate groups. In conclusion, changes in 5-LO enzyme and increased inflammation are related with the disease molecular mechanism. Higher inflammatory status contributes to the impaired hemostatic balance in CCHF. Thus, treatment strategies to reduce inflammation may help to prevent bleeding and DIC in patients. IL-6 and ferritin can be used to as an additional biomarker in the estmation of the prognosis and diagnosis of the patients.     

Synthesis,in silico and in vitro studies of hydrazide-hydrazone imine derivatives as potential cholinesterase inhibitors

A series of hydrazide-hydrazone imine derivative compounds (3a–k) were synthesized and their structures characterized using FTIR, ¹H, and ¹³C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC₅₀ = 2.01 μM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC₅₀ = 2.60 μM). Against BChE, compound 3h (IC₅₀ = 2.83 μM) showed the best inhibitory property which is higher control Galantamine (IC₅₀ = 3.70 μM). The Ki values of compound 3i (Ki = 0.63 μM) and compound 3h (Ki = 0.94 μM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of −10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is −8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.     

A case of inflammatory pseudotumor in the spleen

A case of an inflammatory pseudotumor of the spleen is presented. A 43-year-old woman was hospitalized for a detailed examination due to pancytopenia, which was diagnosed during an examination related to left upper quadrant abdominal pain. Physical examination revealed a 2 to 3 cm splenomegaly. Reticulocyte count was 4% and erythrocyte sedimentation rate was 55 mm/h. No other important findings were noted, except for an evident increase in myeloid series and megakaryocytes (more evident in erythroid series) on bone marrow aspiration and biopsy. Computed tomography (CT) scan revealed splenomegaly and a centrally located hypodense lesion with a 92 X 86 mm axial diameter in the spleen. With a hematologic malignancy prediagnosis, a splenectomy was performed on the patient because of pancytopenia and splenomegaly. An intrasplenic, centrally located, well-limited, capsulated lesion (9.5 x 11 x 10 cm in diameter) was discovered on macroscopic examination of the material. A cellular infiltration area was seen on microscopic examination. The spleen capsule was mildly fibrotically thickened. The lesion that separated from the spleen tissue consisted of diffusely proliferated fusiform fibroblasts, heterogenous inflammatory cells consisting mainly of plasma cells, lymphocytes, sparse neutrophils and vascular elements. No granuloma or multinuclear giant cells were detected. Pancytopenia improved on follow-up. The patient followed up for two years, is now healthy and has no complaints.