The effects of N-acetylcysteine on experimentally created l-asparaginase-induced liver and pancreatic damage in rats.

In this study, oxidative stress marker (malondialdehyde, MDA) and antioxidant enzymes (glutathione (GSH), catalase (CAT)) levels in the liver and pancreas tissue and the histopathological effects of N-acetylcysteine (NAC) were investigated in l-asparaginase (l-ASP) induced liver and pancreatic damage in rats. Forty male albino rats were divided into four groups. The control group was intraperitoneally injected physiological saline (0.02 mL/g); NAC group was injected NAC (200 mg/kg, five days); l-ASP group was injected single-dose l-ASP (10,000 U/kg), and l-ASP + NAC group was injected NAC for five days following single-dose l-ASP (10,000 U/kg). The surgical operation was performed on all animals on the fifth day. There was no difference between the groups regarding tissue MDA, GSH, and CAT levels (p>.05, for all). In the group receiving NAC after l-ASP, there was a significant improvement in the liver and pancreas damage score than the l-ASP group. NAC was effective in reducing organ damage caused by l-ASP.

Evaluation of Total Antioxidant Capacity and Total Oxidant Status of Preterm and Term Breast Milk during the Course of Lactation and within a Nursing Session.

OBJECTIVE: Breast milk (BM) contains antioxidant molecules which may offer protection against oxidative stress (OS). We aim to investigate oxidant-antioxidant balance in preterm BM during the course of lactation and within a nursing session. STUDY DESIGN: Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in colostrum, transitional, and mature BM samples of preterm infants born earlier than 34th week of pregnancy and healthy term infants. Oxidative stress index (OSI) was calculated. Foremilk and hindmilk samples were collected separately. RESULTS: In colostrum and transitional milk, TAC (p < 0.001 and p = 0.001, respectively) and TOS (p = 0.005 and p < 0.001, respectively) were lower in preterm BM compared with term BM. OSI was also lower in preterm BM, but it was statistically significant only in transitional milk (p < 0.001). TAC was highest in colostrum and decreased through the course of lactation. However, the decrease in TAC was not statistically significant in preterm BM. Lowest values of TOS and OSI were observed in colostrum. In transitional term BM, hindmilk had a better oxidant-antioxidant profile as indicated by lower TOS and OSI. CONCLUSION: Oxidant-antioxidant balance is preserved in BM in every stage of lactation. Preterm BM has lower OSI which may offer benefits to preterm newborn against OS.

A new approach for diagnosing hematological malignancies using monocytosis workflow optimization and abnormal lymphocyte/blast flag of Sysmex XN series of blood count analyzers.

INTRODUCTION: Monocytosis Workflow Optimization rule set has been developed by using mono-dysplasia-score to determine reactive monocytosis and prevent unnecessary blood smear of these patients and for detection of chronic myelomonocytic leukemia cases during complete blood count. In our study, we aimed to examine the contribution of Monocytosis Workflow Optimization rule set. METHODS: Adult patients with monocyte count ≥1.0 103 /µL and monocyte percentage ≥10% were included in our study. Blood smears were made from the samples in our laboratory. These smears were examined and patients were divided into two groups as reactive monocytosis or hematological malignancy. The groups were compared in terms of Monocytosis Workflow Optimization rule set and device flags. RESULTS: Twenty-one patients had hematological malignancies of 155 patients who were included in our study. Monocytosis Workflow Optimization rule set suggested performing blood smear in 19 of the patients with hematological malignancy, and evaluated two patients as reactive monocytosis with 90.5% sensitivity and 76.9% specificity. There was an "abnormal lymphocyte/ blast" flag in 90.5% of patients with hematological malignancies and in patients whose Monocytosis Workflow Optimization rule set defined as reactive monocytosis and it was found that sensitivity and negative predictive value reached 100%. CONCLUSION: Automated validation support systems and softwares developed especially for these systems make it possible to classify patients with their non-specific findings, as a result both contributing to the reduction of laboratory workload and costs and assisting laboratory specialists and clinicians with adding value to laboratory results.

Comparison of measured and calculated osmolality levels.

BACKGROUND: Serum osmolality levels are measured to determine acid-base and electrolyte imbalance in serum. In cases where measurement is not possible, the serum osmolality value can be calculated by various calculation methods. In this study, we compared the Worthley osmolality calculation method which is used most frequently mentioned in literature and the measurements made with vapor pressure osmometer used in our laboratory. We compared whether there was a difference between the results obtained by measurement and calculation method in different age groups. METHODS: 221 serum samples of patients who were admitted to the Eskisehir Osmangazi University Hospital Biochemistry Laboratory between December 2016 and May 2018 were included in this study. Glucose, blood urea nitrogen and sodium values were recorded to determine the calculated osmolality values of the patients. RESULTS: There was a statistically significant difference between the measured osmolality values and the calculated osmolality values of the patients (p < 0.001). When compared according to age groups, there was a significant difference between calculated osmolality values (p = 0.006), but there was no difference in measured osmolality values (p = 0.787) in different age groups. It has been observed that this difference in the calculated osmolality values between the age groups is derived from the adult group (18-65, p < 0.001). CONCLUSION: Our results showed that it is not reliable to calculate serum osmolality values, especially in the adult age group. According to our results the calculated osmolality values are higher than our measured osmolality values.

Insulin resistance and pancreatic ß cell dysfunction are associated with thyroid hormone functions: A cross-sectional hospital-based study in Turkey.

BACKGROUND AND AIMS: The prevalence of thyroid disease in diabetic patients is significantly higher than the general population. This indicates a possible interaction between thyroid functions and insulin sensitivity. This study aimed to investigate the relationship between insulin resistance (IR), pancreatic ß cell function, and thyroid function tests. METHODS: This cross-sectional study was conducted with adults who applied to Eskisehir Osmangazi University Hospital for general control. Fasting insulin, glucose, TSH, fT3, and fT4 levels in the serum of 1340 adult (18-60 aged) patients without any chronic diseases were examined retrospectively. The fT3/fT4 ratio, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and HOMA-ß values were calculated. The correlation between HOMA-IR and HOMA-ß values with thyroid function tests and differences between hormone levels of patients with and without IR were evaluated. RESULTS: There was a positive correlation between HOMA-IR and TSH, negative with fT4. Also, a positive correlation between HOMA-ß and fT3, negative correlation with fT4 were observed. In the IR group, fT3 levels were found significantly higher and fT4 levels were significantly lower. TSH levels were higher in the IR group but not statistically significant. The fT3/fT4 ratio was found significantly higher in the IR group and was correlated positively with both HOMA-IR and HOMA-ß. CONCLUSION: Our results revealed that thyroid dysfunction prevalence is quite high in adults who have not yet been diagnosed with diabetes but have insulin resistance and the onset of pancreatic ß cell dysfunction.

Assessment of Phosphate and Osmolarity Levels in Chronically Administered Eye Drops

Objectives: To assess phosphate and osmolarity levels of chronically administered eye drops commercially available in Turkey. Materials and Methods: A total of 53 topical eye drops including 18 antiglaucoma drugs, 4 nonsteroidal anti-inflammatory drugs (NSAIDs), 10 corticosteroids, 7 antihistaminics, and 14 artificial tears identified using the Vademecum Modern Medications Guideline (2018) were included in the study. Phosphate levels were assessed using Roche Cobas C501 analyzer (Roche Diagnostics GmbH, Mannheim, Germany) and the respective kits. Osmolarity was assessed using Vescor Vapro 5600 vapor pressure osmometer (Sanova Medical Systems, Vienna, Austria). Mean phosphate and osmolarity levels were obtained after averaging three measurements. Eye drops were categorized as isoosmolar, hypoosmolar and hyperosmolar based on physiologic tear osmolarity range (296.5±9.8 mOsm/L). Results: The highest phosphate concentration was found in the antiglaucoma group (20.3±35.4 mmol/L), followed by antihistaminics (17.3±17.9 mmol/L), corticosteroids (15.2±19.1 mmol/L), artificial tears (0.8±1.0), and NSAIDs (0.04±0.08). Percentage of medications in the hyperosmolar category was highest in the NSAI group (75%), followed by antihistaminics (43%), corticosteroids (20%), and antiglaucoma drugs (19%). Nearly all of the artificial tear formulations were in the hypoosmolar (71%) or isoosmolar (21%) categories. Conclusion: Approximately 40% of glaucoma medications and approximately 60% of corticosteroid and antihistaminic medications had a phosphate concentration higher than the physiologic tear phosphate level (1.45 mmol/L).

The predictive value of procalcitonin, C-reactive protein, presepsin, and soluble-triggering receptor expressed on myeloid cell levels in bloodstream infections in pediatric patients with febrile neutropenia.

Özdemir ZC, Düzenli-Kar Y, Canik A, Küskü-Kiraz Z, Özen H, Bör Ö. The predictive value of procalcitonin, C-reactive protein, presepsin, and soluble-triggering receptor expressed on myeloid cell levels in bloodstream infections in pediatric patients with febrile neutropenia. Turk J Pediatr 2019; 61: 359-367. The present study investigates the predictive value of procalcitonin (PCT), C-reactive protein (CRP), presepsin (PRE-SEP) and soluble-triggering receptor, as expressed on myeloid cells (sTREM-1) levels in bloodstream infections in pediatric patients with febrile neutropenia. A total of 47 episodes of febrile neutropenia that developed in 30 children with malignancy were analyzed in this study, while the control group comprised 27 children who had undergone chemotherapy for malignancy (completed ≥2 years ago) without neutropenia, fever or drug use. Median PCT, CRP, PRE-SEP and sTREM-1 levels on admission were found to be significantly higher in the patient group than in the control group, while in the blood cultures, the microbiological agent was isolated in 13 (27.7%) of the 47 episodes. Median PCT and CRP levels on days 1, 2 and 7 were higher in the blood culture-positive episodes than in the blood culture-negative episodes. There was no significant difference in the PRE-SEP and sTREM-1 levels on days 1, 2 and 7 between the blood culture-positive and blood culture-negative episodes. The results of the study suggest that PRESEP and sTREM-1 are at measurable levels upon admission in children with febrile neutropenia, but that these markers may not be appropriate for the predicting of bloodstream infections, although CRP and PCT levels within the first 24 hours may serve as a guide for clinicians.

Effects of betaine supplementation on nitric oxide metabolism, atherosclerotic parameters, and fatty liver in guinea pigs fed a high cholesterol plus methionine diet.

OBJECTIVE: The aim of this study was to investigate the effect of high cholesterol (CHOL) and CHOL + methionine (MET) diets on atherogenic and oxidative index parameters and on the factors that influence nitric oxide (NO) bioavailability. Also, attempts were made to determine whether dietary betaine (BET) resulted in any improvement in the changes that occurred after CHOL + MET administration. METHODS: Guinea pigs were fed chow containing 1.5% CHOL with or without 2% MET for 10 wk. A third group received the CHOL + MET + BET diet. Control groups were given standard chow or standard chow + BET. Arginine, NO, nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) levels; lipid profile; and dimethylarginine dimethylaminohydrolase (DDAH) activity were measured. The liver and aorta were subjected to histopathologic analysis. RESULTS: The CHOL + MET diet caused higher serum CHOL and homocysteine levels, but no further increases were seen in aortic CHOL and diene conjugate (DC) levels and histopathologic lesions as compared with the CHOL group. Hepatic lipids and DC levels were also higher, and histopathologic lesions were more severe. CHOL + MET feeding increased ADMA and NT levels as compared with those of the CHOL-fed group. When BET (1 g/kg body weight/d) was added to the CHOL + MET diet, homocysteine and lipid levels decreased and histopathologic changes were reversed. BET diet decreased serum ADMA and hepatic and aortic DC levels and partly restored DDAH activity. CONCLUSIONS: BET supplementation may be effective in preventing hyperlipidemia, disturbed NO availability, oxidative stress, and the development of fatty liver and atherosclerotic lesions that might result from excess amounts of cholesterol and methionine in the diet.

Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children.

BACKGROUND: The aim of the present study was to determine relationship of ischemia-modified albumin (IMA) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) to appendicitis in children. METHODS: Study included total of 63 patients who presented at hospital between May 2015 and November 2015. Of these, 30 were cases of appendicitis, and 33 were healthy control subjects. The groups were statistically similar in age and gender. RESULTS: Receiver operating characteristic curve was evaluated for IMA, CRP, ESR, WBC, MPV, NLR, and PLR values in patients with appendicitis, and IMA was determined to have highest area under the curve value (0.991), followed by NLR (0.946), CRP (0.808), PLR (0.779), ESR (0.767), WBC (0.749), and MPV (0.583). CONCLUSION: Use of NLR, PLR, IMA, and ESR values may be helpful in diagnosis of appendicitis, in addition to WBC and CRP values, lower right quadrant abdominal pain, and ultrasonography signs commonly used.

Circulating levels of apelin, glucagon-like peptide and visfatin in hypercholesterolemic-hyperhomocysteinemic guinea-pigs: their relation with NO metabolism.

The aim of this study was to determine the levels of regulatory peptides apelin, glucagon-like peptide (GLP-1) and visfatin in hypercholesterolemic and hyperhomocysteinemic state and to examine their relation with nitric oxide (NO) metabolism. 32 Male guinea pigs were divided into four groups and each group was fed as follows: (a) commercial chow, (b) cholesterol (chol)-rich diet, (c) methionine (meth)-rich diet, and (d) chol + meth-rich diet. Blood samples were drawn at the end of 10 weeks, and abdominal aorta was dissected for histopathological examination. Serum insulin, GLP-1, apelin, visfatin, and nitrotyrosine concentrations were measured by the manufacturer's kits based on ELISA; asymmetric dimethylarginine (ADMA) and arginine levels were measured by the high performance liquid chromatography. Homocysteine level was measured by the chemiluminescence immunoassay; glucose, total chol and triglyceride levels were measured by the autoanalyzer. The microscopic examination of aorta indicated varying degrees of vascular disturbance in chol- and chol + meth-fed groups. High levels of chol and homocysteine, accompanied with significantly low levels of apelin and GLP-1 were detected in the plasma. Visfatin, ADMA, and nitrotyrosine levels both in chol- and chol + meth-fed groups were significantly higher than those in control animals, whereas arginine and arginine/ADMA ratio were lower. This study indicated that circulating levels of apelin, GLP-1, and visfatin are markedly altered during the development of atherosclerotic changes in close association with chol, homocysteine, NO, and ADMA levels. The measurements of these peptides in serum may help for the diagnosis and follow-up of vascular dysfunction.

Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury.

AIMS: We aimed to investigate the pharmacological efficiency of metformin on asymmetric dimethylarginine (ADMA) metabolism in inflammation caused by the lipopolysaccharide (LPS)/D-galactosamine (D-GalN) treatment. METHODS: Adult Sprague-Dawley rats were injected LPS/D-GalN intraperitoneally. One half of the animals was injected metformin (250 mg kg(-1) body mass for one week) prior to LPS/D-GalN treatment. Six hours after the LPS/D-GalN injection, livers were removed, and used for the measurements of dimethylarginine dimethylaminohydrolase (DDAH) and myeloperoxidase (MPO) activities, glutathione (GSH), ADMA and arginine levels. Liver tissues were examined histopathologically. The Kruskal-Wallis (posthoc Mann-Whitney U) test was used for the statistics. LPS/D-GalN injections caused liver injury as evidenced by the activities of aminotransferases and arginase. GSH level and DDAH activity were decreased in the liver. Metformin pretreatment alleviated the activity of serum enzymes, and attenuated histopathological lesions caused by LPS/D-GalN injections. LPS/D-GalN-induced inflammation, as confirmed by the increased MPO activity, created an asymmetrical distribution of arginine and ADMA between the tissue and plasma. Metformin decreased tissue ADMA level while it restored the DDAH activity and GSH. CONCLUSION: Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/D-GalN-induced injury.

Modulation of arginine and asymmetric dimethylarginine concentrations in liver and plasma by exogenous hydrogen sulfide in LPS-induced endotoxemia.

Plasma levels of asymmetric dimethylarginine (ADMA) are known to be elevated under pathological conditions, but reports on intracellular ADMA levels are scarce. In this study, we investigated whether lipopolysaccharide (LPS)-induced endotoxemia alters the intra- and extra-cellular partition of l-arginine and ADMA. The effect of H2S pretreatment was also researched. Wistar rats were given sodium hydrogen sulfide (NaHS, 1 mg·(kg body mass)(-1)) one hour before the LPS injections (20 mg·kg(-1)). Six hours after the LPS treatment, the animals were sacrificed. Myeloperoxidase (MPO) and dimethylarginine dimethylaminohydrolase (DDAH) activities and levels of hypoxia-inducible factor (HIF)-1α were measured in the liver. ADMA and arginine levels were determined using HPLC. LPS injection caused liver injury, as evidenced by the activities of alanine transaminase, aspartate transaminase, and arginase. LPS increased l-arginine content and decreased DDAH activity in the rat liver. MPO activity and HIF-1α levels indicated inflammation and hypoxia. Despite the accumulation of ADMA in the plasma, the level remained unchanged in the liver. NaHS pretreatment restored both the DDAH activity and intracellular l-arginine levels. It is concluded that increased H2S generation has a potency to restore hepatic l-arginine levels and ADMA handling in endotoxemia. Extra- and intra-cellular partitions of ADMA seem to depend on transport proteins as well as the DDAH activity.

The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients.

The aim of this study was to evaluate the prognostic and predictive efficacy of the human epididymis secretory protein 4 (HE4) and serum amyloid-A (S-AA) together with the other tumor markers (CA 125, CA 15-3, CEA, and CA 19-9) in endometrial cancer patients. The study group consisted of 64 patients with defined stage and grade of endometrial cancer and 60 women with benign uterine diseases. Thirty-four healthy women were defined as the control group. Fasting blood samples were collected prior to surgery and tumor marker levels were determined in blood samples by E170 autoanalyzer. S-AA concentrations were measured by particle-enhanced immunonephelometry. Preoperative serum HE4 and S-AA levels were significantly higher in endometrial cancer patients than in controls, whereas the other measured parameters were not significantly different. Serum levels of HE4 were related to both the stage and grade of tumor. The best cutoff point for HE4 was determined to be 59.7 pmol/L; with 75 % sensitivity and 65.5 % specificity. For S-AA, the cutoff point was 8.8 U/mL, with 68.7 % sensitivity and 58.6 % specificity. The combination of HE4, CA 125, CEA, and S-AA raised the sensitivity to 84 %. Preoperative measurement of serum HE4 and S-AA may be of help in early detection of endometrial cancer. Preoperative screening with these markers may provide important information about the patient's outcome and prognosis.

Effect of carnosine treatment on oxidative stress in serum, apoB-containing lipoproteins fraction and erythrocytes of aged rats.

One of the mechanisms underlying the aging process is proposed to be oxidative damage by free radicals. Carnosine (ß-alanyl-L-histidine) is a dipeptide with antioxidant properties. In this study, we investigated the effect of carnosine supplementation on oxidative stress in serum, apoB-containing lipoproteins (LDL + VLDL) and erythrocytes of young and aged rats. At the initiation of the study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to young and aged rats. We found that serum malondialdehyde (MDA) and diene conjugate (DC) levels and endogenous DC and copper-induced MDA levels in the LDL+ VLDL fraction increased in aged rats, but there was no change in plasma antioxidant activity. Endogenous DC and H(2)O(2)-induced MDA levels were also higher, but glutathione (GSH) levels were lower in erythrocytes of aged rats. Administration of carnosine for 1 month to aged rats resulted in decreased levels of MDA and DC in serum, the LDL + VLDL fraction and erythrocytes and increased levels of GSH in erythrocytes. Our findings indicate that in vivo carnosine treatment may be useful for the decrease in aged-induced oxidative stress in serum, the LDL + VLDL fraction and erythrocytes.

Effect of carnosine against thioacetamide-induced liver cirrhosis in rat.

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Oxidative stress has been proposed to be involved in thioacetamide (TAA)-induced liver cirrhosis in rats, that is similar to human disease. In this study we aimed to investigate the role of carnosine on the development of TAA-induced cirrhosis. 200mg TAA/kg body weight has been given i.p. twice a week for three months to female wistar rats. Another group received same dose of TAA in the same pattern plus 2g carnosine/L of drinking water for three months. TAA administration resulted in hepatic fibrosis, significant increases in plasma transaminase activities as well as hepatic hydroxyproline and lipid peroxide levels, while liver glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) protein expressions and activities decreased. Carnosine was found to behave as an antioxidant reducing malondialdehyde (MDA) and diene conjugate (DC) levels although it was not effective on increased transaminase activities and decreased antioxidants. It also did not affect the histopathological changes observed in TAA group. Thus our findings indicate that carnosine appears to attenuate peroxidation as an antioxidant itself but does not seem to prevent the development of TAA-induced cirrhotic process.

Vascular endothelial growth factor -2578 A/C, -460 T/C and +405 G/C polymorphisms in polycystic ovary syndrome.

OBJECTIVE: Vascular endothelial growth factor (VEGF) may be involved in the physiological regulation of ovarian angiogenesis and pathogenesis of polycystic ovary syndrome (PCOS). VEGF -2578 A/C, -460 T/C and +405 G/C single nucleotide polymorphisms (SNPs) are known to be related to VEGF production. STUDY DESIGN: In order to investigate the possible association between VEGF gene and PCOS susceptibility, we analyzed genotype and allele distributions of above mentioned SNPs in 137 patients with PCOS and 155 healthy women. Differences in genotype distributions and allele frequencies in the cases and controls were compared for statistical significance using the chi(2)-test. Haplotype frequencies were estimated using a contingency chi(2)-test. Mann-Whitney U test was used for the statistics of the clinical and biochemical parameters. RESULTS: No significant association between PCOS and the variant alleles of VEGF -2578 (OR: 0.91, 95% CI=0.65-1.26), -460 (OR: 0.78, 95% CI=0.56-1.08), and +405 (OR: 1.25, 95% CI=0.81-1.93) was observed. However, haplotype analysis demonstrated that the frequency of CTG haplotype, was higher among PCOS compared with controls (p=0.019) and that there is a strong linkage disequilibrium (D'=0.873, r(2)=0.752) between -2578 and -460 polymorphisms. CONCLUSIONS: These preliminary results suggest that the -2578, -460 and +405 SNPs of VEGF gene are not significant risk factors for PCOS development alone. However, because of the high VEGF producer CTG haplotype was more frequent among the PCOS, we suppose that investigated polymorphisms--interacting with other genetic and environmental factors--could play a role in the development of PCOS.