Mahir Cengiz

The efficacy of donepezil administration on acetylcholinesterase activity and altered redox homeostasis in Alzheimer’s disease

Alzheimers disease (AD) is a serious multifactorial disorder with progressive neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of the enzyme acetylcholinesterase (AChE), as one of the major therapeutic strategies, is considered to be offering only symptomatic relief and moderate disease modifying effect. We intended to investigate the effects of acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant-antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N-FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox homeostasis in Alzheimer patients also correlated with AChE activity. The AChE activity and PCO, KYN, N-FKYN and DT levels were found to be significantly higher in the AD group than the control group. The FRAP, T-SH and P-SH levels were significantly lower in the AD group than in the control group. The AChE activity was significantly higher both in donepezil treated and untreated groups when compared with the control group. PCO levels were significantly higher in Alzheimers untreated group than the healthy control and donepezil treated groups. AChE activity was positively correlated with PCO, IMA, PAB, KYN and N-FKYN levels and negatively correlated with FRAP, T-SH and P-SH levels in all participants. Our data showed that treatment with donepezil had ameliorating effects on redox homeostasis in Alzheimer patients. AChE inhibition seems to be exhibiting a potent antioxidant role and may inhibit protein oxidation by decreasing AChE activity in AD, thus medicinal natural substances exhibiting the similar mechanism of action with their antioxidant behaviours can be recommended for the emphasis on new drug new drug development. Further clinical and experimental studies are needed to support our current findings and conclusions.

Primary sarcopenia in older people with normal nutrition

ObjectiveThe aim of this study was to investigate the presence of primary sarcopenia in older patients with normal nutrition and to assess the relationships between the primary sarcopenia with anthropometric measurements.Design and methodsIn this prospective clinical cross-sectional study, six-hundred patients who applied to Polyclinic of Geriatrics between dates 2010 and 2011 have been evaluated. The 386 patients who were supposed to have potential secondary sarcopenia were excluded from the study. Age, gender, weight, height, BMI, calf and waist circumference, ongoing medications, additional diseases of the 214 patients included in the study have been surveyed. The sarcopenia criteria of EWSGOP have been applied.ResultsTwo hundred fourteen cases included in the study were composed of 148 female and 66 male subjects. Mean age was 71.8 ± 2.1 years. Sarcopenia was detected in 105 subjects while 109 (51%) were normal. Sixty-four female (61%) and 41 (39%) male subjects were sarcopenic. Normal group included 84 female (77%) and 25 male (23%) subjects. Incidence of sarcopenia was found higher in the female patients (p<0.001). No statistically significant difference was detected between sarcopenic and normal groups with respect to age, height, weight, calf circumference and evaluation tests. Waist circumference was higher in the sarcopenic group than the normal group (p=0.02). When both groups were analyzed for BMI; 53 (51%) of the 105 sarcopenic patients had BMI over 30 kg/m2 while 29 (27%) and 23 (22%) patients had BMI of 25–30 kg/m2 and below 25 kg/m2, respectively. Incidence of sarcopenia was significantly higher in the group with BMI over 30 kg/m2 when compared with the groups with BMI of 25–30 kg/m2 and below 25 kg/m2 (p=0.01).ConclusionSarcopenia that makes older people physically dependent and decreases their quality of life that receive sufficient nutritional support and are also obese should be comprehensively investigated with respect to presence of sarcopenia.

The role of protein oxidation and DNA damage in elderly hypertension

IntroductionThis study aimed to evaluate the role of protein oxidation and DNA damage in the elderly hypertensive (HT) patients.Materials and methodsThis study consisted of four groups: two elderly groups with 30 HT patients and 30 normotensive healthy volunteers, and two young groups with 30 HT patients and 30 normotensive healthy volunteers. Plasma total thiol (T-SH), advanced oxidation protein products (AOPPs), protein carbonyl (PCO), ischemia modified albumin (IMA), urine 8-hydroxy-2′-deoxyguanosine (8-OHdG), and prooxidant–antioxidant balance (PAB) levels were measured.ResultsIn the elderly HT group AOPPs, PCO, 8-OHdG, and PAB were significantly higher than the elderly control group. In the young HT group T-SH levels were significantly lower and the other oxidative stress parameters were significantly higher than the young control group. In the elderly control group AOPPs, PCO, IMA, 8-OHdG and PAB were significantly higher than the young control group. T-SH was significantly lower in the elderly control than the young control group. In the elderly HT group, T-SH levels were significantly lower and AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher than the young HT group.ConclusionProtein and DNA cell damage occurs by oxidation of free radicals throughout life. Our study supports the view that these radicals may be responsible for the development of hypertension with aging process. Urine 8-OHdG levels can be used as a marker for oxidative DNA damage in the elderly hypertensive patients. Finally, our results suggest that oxidative stress may influence both the development and progression of hypertension and aging.

Treatment of patients with immune thrombocytopenia admitted to the emergency room.

Immune thrombocytopenia (ITP) is the most frequent cause of acquired thrombocytopenia. In adult ITP patients, corticosteroids and intravenous immunoglobulin (IVIg) are used as first-line treatment. The aim of the present study was to investigate retrospectively the demographic and etiologic characteristics of patients with ITP admitted to the emergency room at our hospital. Seventy-five adult patients with ITP were included, and demographic data, bleeding characteristics, etiologic features and responses to treatments were evaluated retrospectively. Fifty-six patients (75xa0%) were female, and the median age was 43xa0years. Eighteen patients had a history of ITP, whereas in 57, thrombocytopenia was identified for the first time. During admission, the median platelet count was 5xa0×xa0109/L. Cutaneous and/or mucosal bleeding was the most common clinical feature. High-dose dexamethasone was administered in 60 episodes, whereas IVIg and conventional-dose methylprednisolone were used in nine and six episodes, respectively. The overall response rate of the entire cohort following first-line treatments was 67xa0%, and complete remission was achieved in 31 patients, 19 patients achieved partial remission, and 25 patients were non-responders. In cases with life-threatening bleeding, concomitant infection, post-traumatic bleeding and need for emergency surgery, IVIg can be used as the first line of treatment option in addition to platelet transfusions.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

Aims Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy. Methods The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated. Results Severe MF (grade II–III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12u2005months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12u2005months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12u2005months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18u2005months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0–I) and severe (grade II–III) groups (p=0.278). Conclusions According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

Analysis of thrombosis and bleeding complications in patients with polycythemia vera: a Turkish retrospective study

The aims of this study are to determine the incidence and risk factors of thrombosis and bleeding in polycythemia vera (PV) patients and to research the effects of these risk factors on survival. The medical records of 155 PV patients were analyzed retrospectively. Patients were divided into groups according to whether or not thrombosis had developed in follow-up, and according to whether or not bleeding had occurred during follow-up. The mean age at diagnosis was 53xa0years, and the mean follow-up period was 66xa0months. The percentage of cases in which thrombosis events had occurred before diagnosis and during follow-up were 26 and 28xa0%, respectively. Comparisons of disease duration and average thrombosis risk score between groups with or without thrombosis drew statistically significant results. A patient’s history of thrombosis and thrombocytosis at first visit was found to have a significant effect on thrombosis recurrence. The major bleeding rate was 8xa0%. Post-PV myelofibrosis was an independent risk factor for bleeding. The major cause of death among the patients in this study was primary thrombosis. The most important causes of mortality among PV patients are thrombosis, and the most prominent risk factors for thrombosis development are disease duration and high thrombosis risk scores. Thrombocytosis in patients with a history of thrombosis may cause thrombosis recurrence during the follow-up period.

Relation of ambulatory blood pressure measurement and cognitive functions in hypertensive elderly patients

IntroductionHypertension is an important risk factor for dementia as much as the morbidity and mortality of cardiovascular disease. Sustained hypertension is also more related to that risk. The aim of the study was to determine the relationship between 24-h ambulatory blood pressure monitoring (ABPM) and cognitive functions in elderly hypertensive patients without comorbid diseases which may deteriorate cognitive functions.Materials and methodsNinety-one patients (21 male, 72.5xa0±xa08.1;70 female, 71.7xa0±xa07.7) above 60xa0years old previously diagnosed as hypertensive (HT) have been included to this study. The ABPM was performed after standardized mini mental test (sMMT) and geriatric depression scale (GDS) has been examined. The patients were divided into the groups as dipper/nondipper and regulated/nonregulated. The sMMT scores of the groups were compared.ResultsThere was no statistical difference in average sMMT scores and distribution of mini mental groups between the dipper and nondipper groups. Hypertension regulation and mini mental measurements of the studied groups were moderately suggestive in the same direction (rxa0=xa00.333, pxa0=xa00.001).Discussion and conclusionThere is an association between tension regulation and cognitive functions in elderly patients who have primary HT, but no relationship have been found between being nondipper and low cognitive function. Our results suggested that this study is critically important by means of revealing that the studies which are perceived distinctly about HT and cognitive functions need further evaluation with subgroup analyses in selected patient groups.

The role of TMPRSS6 gene variants in iron-related hematological parameters in Turkish patients with iron deficiency anemia

TMPRSS6 gene mutations can result in iron deficiency anemia (IDA) and cause an increased iron-regulatory hormone, hepcidin, levels. TMPRSS6 encodes a serine protease, matriptase-2, which functions as negative regulatory protein of hepcidin transcription. Thus, TMPRSS6 variations might be risk factors for IDA. The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters. The study consisted of 150 IDA patients and 100 healthy controls. We analyzed the genotype distributions by using Real-Time polymerase chain reaction (Real-Time PCR) technique. We did not find any statistically differences for all SNPs between patients and controls (Pu202f>u202f0.05). In IDA patients, variations rs855791 and rs2413450 were associated with increased RBC (Pu202f=u202f0.03) and TIBC (Pu202f=u202f0.04), respectively. Also, increased of TIBC for rs4820268 (Pu202f<u202f0.05). On the other hand, in control group, rs5756506 was associated with two parameters, Hb (Pu202f=u202f0.02) and Hct (Pu202f=u202f0.03). We did not find markedly hepcidin levels in IDA patients compared to controls (Pu202f=u202f0.32). Our findings suggest that TMPRSS6 variations may not be risk factors for IDA. However, TMPRSS6 polymorphisms are associated with increased many iron-related hematological parameters.

Ambulatory blood pressure monitoring in living kidney donors: What changes in 10 years?

In renal transplantation, living donations have more significant benefits compared to cadaveric donations. However, a probable increase in blood pressure following donation should also be kept in mind. In this study, we investigated the long‐term changes in blood pressure in living kidney donors using ambulatory blood pressure monitoring and we explored the e‐GFR and albuminuria/proteinuria measurements at 3 time points. Twenty‐eight living kidney donors and 39 healthy individuals were evaluated and compared at the baseline and later at the 10th year. At the 10th year, creatinine levels were higher and eGFR levels were lower in the donors, whereas the systolic and diastolic measurements of the donors and controls and the prevalence of nondipping in the donors and controls were similar. Our study may be underpowered due to its small population size. However, our results at the 10th year follow‐up indicated that the risk of hypertension might not seem to have increased in the well‐selected donors. In addition, the majority of our donors had preserved their GFR values. Therefore, we can suggest that living kidney donation appears to be safe in well‐selected patients over a 10‐year time frame.

Comparison of (18)F-fluorodeoxyglucose PET/CT findings with vascular endothelial growth factors and receptors in colorectal cancer.

The purpose of this study was to evaluate the association of 18F-fluorodeoxyglucose (FDG)-PET/CT findings with the vascular endothelial growth factor (VEGF) family and its receptor (VEGFR) levels in metastatic and nonmetastatic colorectal cancer (CRC). Fluorine-18 FDG-PET/CT scans were performed for initial staging and restaging of patients with CRC. FDG-PET/CT findings of tumor (such as the presence of a primary tumor, the lymphatic or distance metastases, and the maximum standardized uptake value (SUVmax) of the primary tumor), serum VEGF A-C-D-E levels, and serum VEGF receptor 1-2-3 levels were analyzed. A total of 63 patients were included into the study (35 males, mean age 61.3u2009±u200911.9xa0years). Patients were divided into two groups, based on positive and negative PET/CT findings. Patients were also categorized according to the presence of metastasis. All evaluated parameters were significantly higher in the PET/CT-positive group than the PET/CT-negative group (pu2009<u20090.001). All those parameters were also positively correlated with each other. The highest correlation for SUVmax of primary tumor was found with VEGFR-3 (pu2009<u20090.001, ru2009=u20090.665). Patients with metastases had high levels of VEGF-D, VEGF-A, VEGF-C, VEGF-E, and VEGFR-3 than those without metastases. These parameters had better specificity and sensitivity values than the SUVmax of the primary tumor for detection of metastases. However, VEGF-D was the best indicator of metastasis in all of those parameters (VEGF-D vs SUVmax; sensitivity 100 vs 100xa0%; specificity 76 vs 76xa0%; AUC 0.903 vs 0.835; pu2009<u20090.001, respectively). Vascular endothelial growth factor family and its receptors were significantly higher in metastatic CRC patients. VEGF-D was the best indicator of metastasis than all VEGF family, VEGFR-3, and primary tumor SUVmax. VEGF family (A-C-D-E) and VEGFR-3 may help to determine the prognosis and management of CRC.