Addressing the heterogeneity in liver diseases using biological networks.

The abnormalities in human metabolism have been implicated in the progression of several complex human diseases, including certain cancers. Hence, deciphering the underlying molecular mechanisms associated with metabolic reprogramming in a disease state can greatly assist in elucidating the disease aetiology. An invaluable tool for establishing connections between global metabolic reprogramming and disease development is the genome-scale metabolic model (GEM). Here, we review recent work on the reconstruction of cell/tissue-type and cancer-specific GEMs and their use in identifying metabolic changes occurring in response to liver disease development, stratification of the heterogeneous disease population and discovery of novel drug targets and biomarkers. We also discuss how GEMs can be integrated with other biological networks for generating more comprehensive cell/tissue models. In addition, we review the various biological network analyses that have been employed for the development of efficient treatment strategies. Finally, we present three case studies in which independent studies converged on conclusions underlying liver disease.

Neurological Presentations in Patients with COVID-19 in Cytokine Storm.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection causes a wide variety of neurological disorders by affecting both central and peripheral nervous systems. The cytokine storm (CS) has been blamed for the development of severe neurological disorders in COVID-19. However, the relationship between COVID-19 CS and neurological manifestations has not been adequately studied. Thus, we aimed to investigate the neurological presentations in patients with COVID-19 CS. METHODS: The study population consisted of hospitalized moderate-to-severe COVID-19 patients. It was divided into two groups CS (36 patients, 29.3%) and non-CS (87 patients, 70.7%) based on significant clinical symptoms, elevated inflammatory marker levels, radiological findings, and interleukin-6 levels (IL-6). RESULTS: The three most common neurological symptoms in the CS group were altered level of consciousness, headache, and unsteadiness. Altered level of consciousness was higher in the CS group (69.4%) than the non-CS group (25.3%) (p:0.001). The frequency of headache was comparable in both groups (p:0.186). The number of patients requiring intensive care unit and intubation was higher in the CS group (p:0.005 and p:0.001). The mortality rate in the CS group (38.9%) was higher than the non-CS group (8.0%) (p:0.001). IL-6, CRP, ferritin, neutrophil-lymphocyte ratio, procalcitonin, and D-dimer levels were higher in the CS group (for all p:0.001) while lymphocyte count was lower (p:0.003). CONCLUSION: The most common neurological presentation in patients with CS was altered level of consciousness. The presence of CS was an independent risk factor for high mortality.

[Neurological disorders in liver transplantation].

Background and purpose: Liver transplantation is the only curative treatment in patients with end-stage liver failure. It has been associated with neurological disorders more frequently than other solid organ transplantations. We aimed to detect neurological disorders in liver transplantation patients and determine those that affect mortality. Methods: One hundred eighty-five patients, 105 with and 80 without neurological disorders, were included in this study. The follow-up was categorized into three periods: preoperative, early postoperative and late postoperative. We analyzed all medical records, including demographic, laboratory, radiological, and clinical data. Results: Neurological disorders were observed in 52 (28.1%) patients in the preoperative period, in 45 (24.3%) in the early postoperative, and in 42 (22.7%) in the late postoperative period. Hepatic encephalopathy in the preoperative and altered mental state in the post-operative period were the most common neurological disorders. Both hepatic encephalopathy (37.5%) and altered mental state (57.7%) caused high mortality (p=0.019 and 0.001) and were determined as indepen-dent risk factors for mortality. Living donor transplantation caused less frequent mental deterioration (p=0.049). The mortality rate (53.8%) was high in patients with seizures (p=0.019). While mortality was 28.6% in Wilson's disease patients with neurological disorders, no death was observed in patients without neurological disorders. Conclusion: We identified a wide variety of neurological disorders in liver transplantation patients. We also demonstrated that serious neurological disorders, including hepatic encephalopathy and seizures, are associated with high morbidity and mortality. Therefore, in order to avoid poor outcomes, hepatic encephalopathy should be considered as a prioritization criterion for liver transplantation.

The relationship between the heart-type fatty acid binding protein levels, carotid intima media thickness and epicardial fat thickness in patients with obstructive sleep apnea syndrome.

INTRODUCTION: In this study, we aimed to evaluate the relationship between carotid artery intima-media thickness, epicardial fat thickness measurement and the levels of heart-type fatty acid binding protein (hFABP) in patients with obstructive sleep apnea syndrome (OSAS). MATERIALS AND METHODS: Ninety-nine newly diagnosed OSAS patients and fifty non-OSAS control subjects were enrolled in this study. In both groups, demographic data such as age, sex, body mass index (BMI) were recorded and carotid intima-media thickness (CMIT) and epicardial fat thickness (EFT) were measured. hFABP levels were determined using the enzyme-linked immunosorbent assay (ELISA) method according to the manufacturer's protocols. RESULT: Patients with OSAS 67% male, 33% female gender is determined. The mean age of control group was 43.28 ± 12.12 years and group of OSAS was 47.85 ± 11.55 years (p= 0.026). In OSAS group; 38 mild OSAS (38.38%), 23 moderate OSAS (23.23%) and 38 severe OSAS (38.38%) patients were identified. In OSAS patients, average of apnea hypopnea index (AHI) was 29.83/hours. A positive correlation was observed between BMI with EFT and CMIT (p< 0.05). hFABP levels in OSAS group average was 2.65 ± 2.1 ng/mL and in control group average was 1.62 ± 0.90 ng/mL and this was statistically significant (p= 0.002). EFT, in the control group average was 5.3 ± 2.04 mm, while the average was 4.3 ± 1.79 mm in the OSAS group (p= 0.019). The correlation was observed between the CMIT and EFT (p< 0.001). There was no significant difference in BMI and gender between OSAS and control groups. No accompanying cardiovascular disease was detected in patients with OSAS. CONCLUSIONS: This study suggests EFT and hFABP can be used as a predictive value in determining cardiovascular risk in OSAS patients.

The role of vitamin B1-B2 and plasma lipid profile in intrahepatic cholestasis of pregnancy.

AIM: The present study aimed to determine the levels of total cholesterol, triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and vitamins B1 and B2 in intrahepatic cholestasis of pregnancy (ICP) patients, and to evaluate if these were involved in the pathophysiology of the disease. METHODS: The prospective randomized study included 35 pregnant patients who were admitted to the Gynecology and Obstetrics Polyclinic, Faculty of Medicine at Dicle University and who were diagnosed with ICP (Group 1), and 40 healthy pregnant women who were admitted in the same period and who had no systemic diseases that might complicate the pregnancy during the pregnancy follow-up (Group 2). Serum lipid levels and vitamins B1 and B2 were determined and compared, and statistical comparisons of the groups were made. RESULTS: There was no difference between the TG levels of the two groups (P=0.631). Total cholesterol, LDL, HDL, and vitamin B1 and B2 levels were higher in Group 1 than in Group 2 (P=0.001, P=0.001, P=0.001, P=0.001, and P=0.032, respectively). CONCLUSIONS: Increased levels of vitamins B1 and B2 may indicate a need for increased energy metabolism at the fetus. So we believe that new studies are required, which will be supported by the placental analyses of the pyruvate and lactate levels in maternal blood at delivery and fetal cord blood in order to develop a better understanding on the fetal effects of energy metabolism.

Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome.

BACKGROUND: We aimed to measure the levels of inflammatory markers and neopterin in obese and non-obese patients with PCOS by using 2 separate control groups with matching body mass index (BMI). MATERIAL AND METHODS: A total of 60 women of reproductive age with (n=30) and without (n=30) PCOS were included in this study. Based on their BMI, patients with PCOS were divided into 2 groups as obese (n=15) and non-obese (n=15) PCOS groups. In addition, 2 BMI-matched control groups were formed. Neopterin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (N/L ratio), and vitamin B12 were assessed by complete blood count. RESULTS: No significant difference was found between patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and CRP levels. However, N/L ratio levels were significantly higher (p 0.045) and vitamin B12 levels were significantly lower (p 0.033) in patients with PCOS compared to control subjects. No statistically significant difference was found between obese and non-obese patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and N/L ratio levels. However, CRP levels were significantly higher in obese patients with PCOS compared to obese control subjects (p 0.007). CONCLUSIONS: It can be concluded that inflammatory activity is increased in patients with PCOS, can lead to an increased risk for atherosclerosis, and this increase is not caused by obesity but rather by the polycystic ovary syndrome itself. However, studies with larger sample sizes are needed in this area.

Serum omentin, resistin and tumour necrosis factor-α levels in Behcet patients with and without ocular involvement.

PURPOSE: The objective of this study was to evaluate serum omentin, resistin and tumour necrosis factor-α (TNF-α) levels in Behcet disease (BD) patients with and without ocular involvement, as well as control subjects. METHODS: Omentin, resistin and TNF-α levels were assessed in the plasma of 51 BD patients and compared with those of 24 control subjects. RESULTS: The plasma resistin and TNF-α levels were significantly higher in the BD patients than in the control group (p = 0.028 and p = 0.011, respectively), whereas the plasma omentin level was significantly lower in BD patients than in the control group (p = 0.035). In the ocular BD, non-ocular BD and control groups, the omentin levels were 8.9 ± 4.65, 8.6 ± 3.61, and 12.4 ± 6.24 ng/mL; resistin levels were 0.29 ± 0.21, 0.24 ± 0.2 and 0.15 ± 0.45 ng/mL; and TNF-α levels were 25.45 ± 3.65, 24.03 ± 2.49 and 21.93 ± 4.86 ng/mL, respectively. Omentin/resistin and TNF-α/omentin ratios were more significant parameters in the demonstration of the differences in the groups; the former was lower and the latter was higher in the patient groups (p = 0.001 and p = 0.002, respectively). CONCLUSIONS: We demonstrated that the plasma omentin level and omentin/resistin ratio were decreased, whereas the resistin and TNF-α levels and TNF-α/omentin ratio were increased in BD patients. These ratios may be used in the presentation of deviation in the inflammatory and anti-inflammatory balance in BD.

Relationship between hepcidin levels and periodic limb movement disorder in patients with obstructive sleep apnea syndrome.

PURPOSE: This study was aimed to assess potential correlations between periodic leg movement (PLM) index, hepcidin levels, and iron status in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Forty-four newly diagnosed OSAS patients and 49 non-apneic controls were enrolled in this study. All patients underwent polysomnographic evaluation. The hepcidin, iron, ferritin, total iron binding capacity, and C-reactive protein levels were measured. RESULTS: The mean age was 47.4 ± 7.2 years (18-68) in the OSAS group and 44.9 ± 11.1 years (23-65) in the control group. There were no differences in age, gender, and smoking between OSAS patients and controls. Mean apnea-hypopnea index (AHI) was 25.1 events/h. Mean serum hepcidin levels were significantly higher in OSAS subjects (725.9 ng/ml) than in control subjects (646.0 ng/ml) (p < 0.001). Serum iron levels were significantly lower in the OSAS and PLM disorder groups than in control subjects (p < 0.001). Serum hepcidin levels were significantly correlated with AHI (r = 0.453) and PLM index (r = 0.114). Serum iron levels were significantly negatively correlated with AHI (r = -0.169) and PLM index (r = -0.180). CONCLUSIONS: In our study, the level of hepcidin was increased in patients with OSAS. Our study indicates that levels of hepcidin correlate with the AHI and PLM index severity of OSAS.

Serum Cytokine Levels in Behçet's Disease.

BACKGROUND: The aim of this study is to investigate and compare the serum levels of various cytokines in patients with Behçet's Disease and healthy controls. METHODS: Thirty-five patients with Behçet's disease and 29 age and sex-matched healthy controls were included in the study. The patients were separated into groups with active and inactive disease. Serum IL-2, IL-6, IL-8, IL-10, IL-17A, and IFN-γ levels were determined using the enzyme-linked immunosorbent assay method. Cytokine levels of the two patient groups and healthy controls were compared using SPSS 15.0. RESULTS: Ten patients with active disease and 25 patients with inactive disease were present. Serum IL-8 levels of active BD patients were higher compared to inactive patients (P = 0.048) and healthy controls (P = 0.02). IL-8 levels were correlated with the duration of symptoms (r = 0.490, P = 0.003) and time passed since diagnosis (r = 0.579, P ˂ 0.001). CONCLUSION: Behçet's disease involves complex interactions of cells of the immune system, mainly T lymphocytes and neutrophils. Further studies on the cytokine profile in Behçet's disease will aid in elucidation of its pathogenesis.

Honokiol decreases intra-abdominal adhesion formation in a rat model.

AIM: The purpose of this study was to investigate the effectiveness of honokiol, a natural molecule that was shown to have antioxidant effects, in prevention of intra-abdominal adhesion formation in a rat model. MATERIAL AND METHOD: This study was conducted on a total of 40 non-pregnant Sprague-Dawley rats, which were divided into 4 groups as follows: sham, control, saline, and honokiol groups. Both uterine horns of the rats in control, saline, and honokiol groups were exposed and a 2-cm segment of the anti-mesenteric surface of both uterine horns was traumatized by a scalpel. The saline group was administered 2 ml of saline/day intraperitoneally for 5 days after the operation. The honokiol group, on the other hand, was administered honokiol intraperitoneally at a dose of 1 mg/kg/day for 5 days after the operation. On postoperative day 14, 3 ml of intracardiac blood sample was taken from the rats for biochemical analyses, and the rats were sacrificed this way. RESULTS: Adhesion and inflammation scores were significantly lower in the honokiol group compared with the saline and control groups (p < 0.008). Similarly, fibrosis score was significantly lower in the honokiol group compared with the saline group (p < 0.008). CONCLUSION: Honokiol was found to be effective in prevention of intra-abdominal adhesion formation in a rat model. However, larger studies are needed to shed light on the exact role of honokiol in intra-abdominal adhesion formation and to determine the molecular aspects of the promising results found in this study.

Effect of intraperitoneal curcumin instillation on postoperative peritoneal adhesions.

OBJECTIVE: The aim of this study was to determine the effect of curcumin on adhesion formation in a rat cecum abrasion model. MATERIALS AND METHODS: Thirty Wistar rats were randomized into three groups; the control group received saline, the curcumin group received 10 mg/kg of curcumin after cecal abrasion, and in the sham group the abdominal wall was closed without any abrasion to the cecum. On day 15, adhesions were assessed blindly using a standardized scale, and histopathological samples were taken and examined. RESULTS: There were no incisional hernias or wound dehiscences in any animals of the three groups. A comparison of adhesion scores showed a significant difference between the curcumin (median = 1) and the control group (median = 2; p < 0.05). The grade of inflammation of the curcumin (median = 1) and the sham (median = 0) group was significantly lower than that of the control group (median = 3; p < 0.01 and p < 0.001, respectively). Hydroxyproline levels were significantly lower in the sham (48.3 ± 11.8 µg/mg) and the curcumin (63.8 ± 13.9 µg/mg) group compared to the control group (85.7 ± 22.1 µg/mg; p < 0.05). CONCLUSION: These data suggest that curcumin, administered intraperitoneally, was effective in the prevention of peritoneal adhesion formation.

Low fetuin-A level in migraine: a case-control study.

Migraine is a type of primary headache which is caused by the alterations in trigeminovascular system. Migraine attacks are associated with neurovascular inflammation of the cerebral and extracerebral vessels, but its pathophysiological mechanisms have not still been fully delineated. Also, migraine has been found to be associated with higher risks for various metabolic disorders. Thus, we aimed to investigate the matrix metalloproteinases (MMP), fetuin-A, ghrelin, and omentin levels which have important roles in metabolic disorders and inflammation, and to examine their relationship with migraine subtypes and attack frequency. Forty-nine migraine patients and 30 age- and sex-matched healthy control subjects were enrolled. Migraine diagnosis was confirmed according to the International Classification of Headache Disorders-II diagnostic criteria. Analyses of MMP9,MMP3, ghrelin, omentin, and fetuin-A were performed by the ELISA method. Fetuin-A, MMP-9, and MMP-3 levels were significantly lower in migraine than controls (p < 0.05). There were no significant differences between groups with respect to omentin and ghrelin (p > 0.05). In migraine patients, serum fetuin-A levels were positively correlated with MMP-9 and negatively correlated with MMP-3. MMP-3, MMP-9, fetuin-A, omentin and ghrelin levels did not correlate with age, disease duration, or frequency of migraine headache (p > 0.05). Migraine patients have lower fetuin-A, MMP-3 and MMP-9 levels than healthy individuals. Migraine patients have low fetuin-A levels, which may be related to the pathogenesis of migraine. The importance and impact of our findings on the pathogenesis, characteristics, and treatment of migraine needs to be investigated in further detailed studies.

Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats.

PURPOSE: The purpose of this study was to investigate the effect of carvacrol (CAR) on methotrexate (MTX)-induced renal damage in rats. METHODS: Twenty-four male rats were equally divided into three groups: group I, control treatment; group II, MTX-treated; and group III, MTX+CAR-treated. A single dose of CAR (73 mg/kg) was administered intraperitoneally to group III on the first day of the experiment and a single dose of MTX (20 mg/kg) was administered intraperitoneally to groups II and III on the second day of the experiment. Blood samples and kidney tissue were obtained from each animal on day 8 for the measurement of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Light microscopy was used for histopathological examination of kidney specimens. RESULTS: MDA, TOS and OSI levels were significantly greater in the group receiving MTX alone relative to the control animals, while the TAS level was significantly reduced in the MTX group compared with the control group. The administration of CAR was associated with significantly decreased MDA, TOS, and OSI levels and increased TAS levels relative to the rats treated with MTX alone. Animals treated with CAR exhibited decreased tubular degeneration and architectural impairment relative to animals treated with MTX alone; however, the difference in histological scores did not meet the threshold of statistical significance. CONCLUSIONS: MTX treatment results in oxidative damage to the rat kidney; damage which is partially abrogated by the administration of CAR.

Serum dehydroepiandrosterone sulphate, total antioxidant capacity, and total oxidant status in central serous chorioretinopathy.

BACKGROUND: The objective of this work is to evaluate plasma total antioxidant capacity (TAC), total oxidant status (TOS), and dehydroepiandrosterone sulphate (DHEA-S) levels in patients diagnosed with acute central serous chorioretinopathy (CSCR) and control samples. METHODS: The TAC, TOS, and DHEA-S levels were assessed in the plasma of 46 CSCR patients and compared with 40 control samples. RESULTS: The TAC level was 1.16 ± 0.08 and 1.20 ± 0.09 mmol Trolox eq./l; TOS level was 28.77 ± 33.33 and 19.95 ± 10.42 µmol H202/l; DHEA-S level was 203.79 ± 84.75 µg/dl and 249.36 ± 122.93 µg/dl in the CSCR group and in the control group, respectively. The plasma TAC and DHEA-S values were significantly lower in the CSCR group than in the control group (p = 0.027 and p = 0.046, respectively). There was no significant difference between the CSCR and the control groups in terms of age, gender, and TOS levels (p > 0.05). CONCLUSIONS: We demonstrated that the levels of plasma DHEA-S and antioxidative parameters were reduced in CSCR. Our results suggest that the antioxidant defense system may be inadequate or corrupted in CSCR. Reduced DHEA-S level is one of the factors that trigger this insufficiency.

Expression of interleukin-17 in lesions of erythema multiforme may indicate a role for T helper 17 cells.

INTRODUCTION: The aim of this study was to evaluate levels of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-17A and interferon γ (IFN-γ) in the serum of patients with erythema multiforme (EM) and to search for the presence of IL-17-expressing cells in lesional samples of EM. MATERIAL AND METHODS: A total of 32 patients (22 females and 10 males) diagnosed with EM of the minor or major type were included in the study. Levels of IL-2, IL-6, IL-8, IL-10, IL-17A and IFN-γ in the serum were determined and compared with healthy controls. Biopsy specimens were stained with haematoxylin and eosin (HE) and monoclonal antibodies to CD4, CD8 and IL-17 for immunohistochemical examination. RESULTS: IL-2, 6, 8 and 17A were significantly higher in the patient group (p = 0.016, p = 0.001, p = 0.004, p = 0.006, respectively) and levels of IL-10 were significantly lower than in the control group (p = 0.046). The cellular infiltrate in lesions of EM was composed mainly of CD4+ T lymphocytes. The presence of IL-17-expressing cells, at proportion of 5 to 50%, was observed in the infiltrate. CONCLUSIONS: The demonstration of IL-17-expressing cells in lesions of EM in this study has brought forth the assumption that Th17 cells may be involved in the pathogenesis of EM.

The Importance of Long-term Partner Observation in Cognitive Evaluation: A Very Early Creutzfeldt-Jakob Disease in a Patient with Mild Cognitive Impairment.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage. CASE PRESENTATION: A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died. CONCLUSION: Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.

Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury.

This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T + S). The T, T + V and T + S groups were subjected to TBI. The T + V group was administered vehicle [ethanol:saline (1/2)] and the T + S group was administered 1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the T + S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the T + S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the T + S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.

Relationship of cognitive performance with prolidase and oxidative stress in Alzheimer disease.

Glutamate excitotoxicity and oxidative stress are held responsible for the pathogenesis of Alzheimer's disease (AD). Prolidase is known to have a crucial part in the recycling of proline for collagen synthesis. Elevated proline levels have been shown to increase glutamate concentration. To our knowledge, prolidase activity in AD has not yet been studied. In this study, we aimed to reveal the relationship of AD with oxidative stress and collagen turnover by comparing AD patients and healthy control group with regard to total antioxidant status (TAS), total oxidant status (TOS), and prolidase levels. Fifty patients (mean age, 72.5 ± 8.9 years) diagnosed with AD and a control group comprised of 39 healthy individuals (mean age, 69.1 ± 7.1 years) were compared relative to serum TAS, TOS, and prolidase levels. The relationship of cognitive performance with prolidase, TAS, and TOS was evaluated by Mini mental state examination (MMSE). Alzheimer's disease group demonstrated statistically significantly higher prolidase and TOS levels as compared to the control group (p = 0.01, p = 0.018, respectively). Total antioxidant status level was significantly lower in the dementia group than in the control group (p = 0.032). MMSE manifested a negative correlation with prolidase and TOS levels (p = 0.001, r = -0.33; p = 0.002, r = -0.32, respectively), while displaying a positive correlation with TAS levels (p = 0.002, r = 0.32). In conclusion, elevated prolidase and TOS levels along with reduced TAS concentrations suggest that oxidative stress and collagen breakdown are involved in the cognitive impairment in AD.

Comparison of fully automated urine sediment analyzers H800-FUS100 and LabUMat-UriSed with manual microscopy.

BACKGROUND: Recent technical developments have focused on the full automation of urinalyses, however the manual microscopic analysis of urine sediment is considered the reference method. The aim of this study was to compare the performances of the LabUMat-UriSed and the H800-FUS100 with manual microscopy, and with each other. METHODS: The urine sediments of 332 urine samples were examined by these two devices (LabUMat-UriSed, H800-FUS100) and manual microscopy. RESULTS: The reproducibility of the analyzers, UriSed and Fus100 (4.1-28.5% and 4.7-21.2%, respectively), was better than that with manual microscopy (8.5-33.3%). The UriSed was more sensitive for leukocytes (82%), while the Fus-100 was more sensitive for erythrocyte cell counting (73%). There were moderate correlations between manual microscopy and the two devices, UriSed and Fus100, for erythrocyte (r = 0.496 and 0.498, respectively) and leukocyte (r = 0.597 and 0.599, respectively) cell counting however the correlation between the two devices was much better for erythrocyte (r = 0.643) and for leukocyte (r = 0.767) cell counting. CONCLUSION: It can be concluded that these two devices showed similar performances. They were time-saving and standardized techniques, especially for reducing preanalytical errors such as the study time, centrifugation, and specimen volume for sedimentary analysis; however, the automated systems are still inadequate for classifying the cells that are present in pathological urine specimens.

The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve.

PURPOSE: We aimed to test caffeic acid phenethyl ester (CAPE) as an antidote for acute methanol (MeOH) toxicity and to compare it with ethanol. METHODS: This study included five groups, each containing eight rats. The groups were control, methotrexate (MTX), MeOH, ethanol and CAPE. All rats except control group were treated with intraperitoneal (i.p.) MTX (0.3 mg/kg/d) for 7 d. At the 8th day of the experiment, i.p. injection of MeOH (3 g/kg) was administered in MeOH, ethanol and CAPE groups. Four hours after MeOH treatment, 0.5 g/kg ethanol was injected i.p. in ethanol group; 10 µmol/kg CAPE i.p. in CAPE group; serum physiologic i.p. in other groups. After 8 h, rats were anaesthetized and sacrificed. Total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the cell count of retinal ganglion cell (RGC) layer. In addition, interactions of alcohol dehydrogenase with CAPE, ethanol, MeOH and pyrazole derivatives were investigated. RESULTS: Either CAPE or ethanol co-treatment decreased the TOS levels and increased the TAS levels compared to the MeOH group. MeOH treatment decreased the mean cell count in RGC layer. CAPE co-treatment significantly prevented cell loss (p = 0.040). Besides, in silico calculations showed that binding affinity of CAPE to alcohol dehydrogenase was higher than those of MeOH, ethanol, and pyrazole derivatives were. CONCLUSION: This study demonstrated that CAPE treatment decreased the oxidative stress in acute MeOH intoxication in the retina and optic nerve; beside that, protected RGC layer histology. In silico, CAPE had higher affinity score than MeOH, ethanol, pyrazole and pyrazole derivatives in the case of interaction with alcohol dehydrogenase.