Tamer Inal

Macrophage depletion delays progression of neuropathic pain in diabetic animals

Despite the fact that it is a frequent diabetic complication, the mechanisms underlying the manifestation of diabetic neuropathic pain remain poorly understood. In this study, we hypothesized that the depletion of peripheral macrophages with liposome-encapsulated clodronate (LEC) can prevent, at least delay, the progression of diabetes-induced neuropathic pain. Therefore, the aim of this study was to evaluate the effects of macrophage depletion on mechanical allodynia and thermal hyperalgesia in the streptozotocin (STZ)-induced rat model of diabetic neuropathy. LEC was intravenously administrated to rats three times with 5-day intervals. A single intravenous injection of STZ caused an increase in the average blood glucose levels and a decrease in body weight. Although LEC treatment did not affect the body weight gain, the blood glucose level was lower and serum insulin level higher in LEC-treated diabetic rats than in that of diabetic rats. In addition, LEC treatment alleviated the excessive damage in beta cells in diabetic rats. Diabetic animals displayed marked mechanical allodynia and thermal hyperalgesia. While the treatment of diabetic rats with LEC did not significantly change the thermal withdrawal latency, diabetes-induced decrease in mechanical paw withdrawal threshold was significantly corrected by the LEC treatment. The results of this study show that thermal hyperalgesia and mechanical allodynia induced by diabetes may be associated with alterations in blood glucose level. Depletion of macrophages with LEC in diabetic rats may reduce mechanical allodynia without affecting thermal hyperalgesia. Taken together, these results suggested that depletion of macrophages in diabetes may partially postpone the development of diabetic neuropathic pain.

Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet's disease

ObjectiveThe aim of this study was to assess whether homozygosity for the 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation and plasma homocysteine concentration are related to deep vein thrombosis in Behçets disease (BD) patients.MethodsForty BD patients (23 males, 17 females; mean age 40.2±8.4 years) and 60 healthy controls (HC) (34 males, 26 females; mean age 41.6±6.9 years) were included in the study. Fourteen of the BD patients had a history of deep venous thrombosis (DVT), as confirmed by Doppler ultrasound.ResultsThe rates of homozygosity for the MTHFR C677T mutation in the BD and HC groups were 7.5% and 10%, respectively. The distribution of MTHFR genotypes was similar in the two groups (p>0.05), and analysis showed that homozygosity for the mutation was not a risk factor for DVT. The mean plasma homocysteine levels were 13.4±4.2 µmol/l for the overall BD patients and 12.6±3.8 µmol/l for HC (p>0.05). However, the mean plasma homocysteine level in the BD patients with DVT history (15.9±4.6 µmol/l) was significantly higher than the level in the BD patients with no DVT history (12.1±3.3 µmol/l) (p=0.013) and the level in the HC group (12.6±3.8 µmol/l) (p=0.025).ConclusionThe study results suggest that elevated plasma homocysteine level may play a role in the pathogenesis of venous thrombosis in BD.

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

We investigated the effect of rosiglitazone (RSG), a high‐affinity ligand for the peroxisome proliferator‐activated receptor gamma which mediates insulin‐sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)‐induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg−1) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg−1), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA1c and blood glucose levels in the circulation and malondialdehyde (MDA) and 3‐nitrotyrosine (3‐NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time‐dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3‐NT levels. In group D, 3‐NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes‐related vascular diseases, RSG treatment may be cardioprotective. Copyright

The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol.

We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome (ACS) patients with low low-density lipoprotein (LDL) cholesterol level. One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study (mean 78.2 ± 12.3 mg/dl). While 70 randomly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their standard treatment as the atorvastatin group, the remaining 42 patients considered as the control group were given the standard treatment only, i.e., without any lipid-lowering drug therapy. Lipid profile, high-sensitivity C-reactive protein (hsCRP), and plasma amyloid A (SAA) levels were measured in all patients within the first 24 h of chest pain, on the 5th day, and in the 6th month. During the inpatient period and subsequent 6-month follow-up, all episodes of angina, reinfarction, revascularization, heart failure, rehospitalization, cardiac mortality, and total number of cardiac events were recorded. In the atorvastatin group, hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group (P < 0.0001). Mean LDL cholesterol level was significantly decreased in the atorvastatin group (55.7 ± 17.7 mg/dl), but there was no significant change in the control group at the 6th month. The frequency of heart failure during the inpatient period and angina, unstable angina pectoris, heart failure, and revascularization in the first 6 months were also significantly reduced in the atorvastatin group. Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels.

Cardiac troponin T as a prognostic marker in patients with heart failure : a 3-year outcome study.

Cardiac troponin T (cTnT), a highly sensitive and specific indicator of myocardial cell death, may be elevated in congestive heart failure (CHF). The aims of this study were to test the hypothesis that decompensated CHF may be associated with an increase in cTnT release and to correlate between cTnT levels and patient outcomes. The authors studied 55 patients aged between 38 and 86 years (30 women and 25 men) who were hospitalized for CHF. Left ventricular ejection fraction (EF) was calculated by using modified Simpsons rule by echocardiography. cTnT levels were assessed. Troponin T ≥0.1 ng/mL was considered as positive. All patients were contacted by phone annually during the next 3 years, and their history of subsequent hospital admissions and current health status were recorded. cTnT was negative in 44 (80%) and positive in 11 (20%) patients. EF was significantly lower and NYHA was higher in cTnT-positive patients. During the 3-year follow-up period, 25 patients died from CHF. The mortality rate was 8/11 (72.7%) among cTnT-positive patients, whereas the mortality rate was 17/44 (38.6%) among cTnT-negative patients. There were significant relationships among positivity of cTnT, NYHA, EF, and mortality rate. Multivariate regression analysis yielded an independent relationship between positivity of cTnT, NYHA classification, and mortality rate. The percent of hospital admissions due to CHF was also higher in patients with cTnT positive (63.6% versus, 27.3%, p <0.05). In conclusion, this study shows that cTnT positivity is an independent risk factor in predicting the long-term mortality and morbidity rate in patients with CHF. Patients with worsening CHF may possibly be identified early on the basis of their elevated serum cTnT levels.

Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol in renal transplant recipients.

In large patient populations, it has been established that calculated (c) and measured (m) plasma levels of low-density lipoprotein cholesterol (LDL-C) were comparable, but this issue is not known to be tested in renal transplant recipients (RTRs). Herein we aimed to compare the plasma levels of LDL-C that was calculated by Friedewald formula (FF) and direct measurement in RTRs. Methods: LDL-C was measured by direct method and by FF in 193 fasting venous blood samples obtained from 103 RTRs. Patients had triglyceride (TG) levels <400 mg/dL. Patients were treated with prednisolone, calcineurin inhibitors (CNIs), and/or sirolimus and everolimus. Results: The mean plasma levels of LDL-C for calculated and direct measurement were 100.81 ± 32.79 mg/dL and 107.82 ± 33.23 mg/dL, respectively (p < 0.01). The differences between cLDL-C and mLDL-C were similar according to usage of angiotensin receptor blockers (ARB)/angiotensin-converting enzyme inhibitors (ACEI), CNI, or mammalian target of rapamycin inhibitor (mTOR), tacrolimus or cyclosporine, and serum creatinine levels. mLDL-C and cLDL (FF) were highly correlated (r = 0.977). The mLDL-C level was calculated by following formula: LDL-C = 8.018 + (0.99 × FF cLDL-C) and the mean difference was 0 for last formula. Conclusion: The LDL-C can be calculated by the following formula: LDL-C = 8.018 + (0.99 × FF LDL-C). The coefficient of determination correlation (r) for this regression was 0.977, which indicates that the calculated LDL-C levels can be used in RTRs with TG lower than 400 mg/dL. mLDL-C was significantly higher than cLDL-C. We observed that difference between cLDL-C and mLDL-C levels were not affected by serum creatinine levels and usage of CNIs, sirolimus, everolimus, ACEI, and ARB in RTRs.

Biological Variation and Reference Change Value Data for Serum Neuron-Specific Enolase in a Turkish Population

Neuron‐specific enolase (NSE) is a recognized biomarker for the assessment of cerebral injury in neurological disorders. This study aims to report a definitive assessment of the biological variation (BV) components of this biomarker, including within‐subject BV (CVI), between‐subject BV (CVG), index of individuality (II), and reference change value (RCV), in a cohort of Turkish participants using an experimental protocol.

Lean six sigma methodologies improve clinical laboratory efficiency and reduce turnaround times

Organizing work flow is a major task of laboratory management. Recently, clinical laboratories have started to adopt methodologies such as Lean Six Sigma and some successful implementations have been reported. This study used Lean Six Sigma to simplify the laboratory work process and decrease the turnaround time by eliminating non‐value‐adding steps.