Assessment of renal function in clinical medicine is of great importance. Various studies report that cystatin C (cysC) and β2-microglobulin are valuable markers of renal function. In this study, serum cysC and β2-microglobulin were measured in parallel with serum creatinine in a healthy population, and the characteristics of the relationship of cysC and β2-microglobulin to age and gender were compared. Serum creatinine, cysC and β2-microglobulin were measured in 119 (86 female; 33 male, 6 to 69 years old) healthy subjects. They were divided into five different age groups: group 1 (6-15 years, n = 10), group 2 (16-30 years, n = 34), group 3 (31-45 years, n = 34), group 4 (46-60 years, n = 29) and group 5 (>61 years, n = 12). Serum creatinine did not differ among groups and was not correlated with age. Creatinine values were significantly different (p = 0.004) between males and females. CysC values differed neither by gender nor by age in the groups. However, cysC exhibited a positive correlation with age (r = 0.212, p = 0.021). β2-microglobulin levels showed a significant difference between groups (p = 0.036). There was a positive correlation between serum β2- microglobulin and age (r = 0.188, p = 0.041). In conclusion, serum cysC and β2- microglobulin levels in healthy individuals increase with ageing, consistent with the decrease in GFR.
Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 ± 1.01 μmol/l) than in the control subjects (7.05 ± 0.36 μmol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 ± 16.4 ng/l in the control group and 284.3 ± 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 ± 0.58 μg/l and 8.05 ± 0.72 μg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease.
Epilepsy is among the most neurologic disorders. Due to its damaging effects on the brain and the psychological problems that it creates in the patients, it deserves extensive study of its pathogenesis and new therapeutical approaches. The most widely accepted hypothesis on the pathogenesis of epilepsy is a failure in the regulation of excitatory and inhibitory mechanisms in the brain. The aim of this study was to assess the levels of amino acids in cerebrospinal fluid (CSF) which was believed to reflect the levels of excitatory amino acids in the brain. CSF glutamate, aspartate and glycine levels were determined by gas -liquid chromatography in 12 epileptic patients (juvenile myoclonic epilepsy (JME) n=7, idiopathic primary generalized epilepsy with tonic clonic seizuren=5) and 12 controls. In the epileptic patients, glutamate and glycine levels were significantly higher than controls (p The findings of this study suggest that further studies with a larger patient population and comparison of levels in CSF and epileptogenic brain tissue would be useful for a better understanding of the role excitatory amino acids in the pathogenesis of epilepsy.
Abstract Objectives The present study describes clinical, biochemical, molecular genetic data, current treatment strategies and follow‐up in nine patients with tetrahydrobiopterin (BH4) deficiency due to various inherited genetic defects. Methods We analyzed clinical, biochemical, and molecular data of nine patients with suspected BH4 deficiency. All patients were diagnosed at Ege University Faculty of Medicine in Izmir, Turkey and comprised data collected from 2006 to 2019. The diagnostic laboratory examinations included blood phenylalanine and urinary or plasma pterins, dihydropteridine reductase (DHPR) enzyme activity measurement in dried blood spots, folic acid and monoamine neurotransmitter metabolites in cerebrospinal fluid, as well as DNA sequencing. Results Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency, two with 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency, three with sepiapterin reductase (SR) deficiency, and three with DHPR deficiency. Similar to previous observations, the most common clinical symptoms are developmental delay, intellectual disability, and movement disorders. All patients received treatment with l ‐dopa and 5‐hydroxytryptophan, while only the ar GTPCH, the PTPS, and one DHPR deficient patients were supplemented in addition with BH4. The recommended dose range varies among patients and depends on the type of disease. The consequences of BH4 deficiencies are quite variable; however, early diagnosis and treatment will improve outcomes. Conclusions As BH4 deficiencies are rare group of treatable neurometabolic disorders, it is essential to diagnose the underlying (genetic) defect in newborns with hyperphenylalaninemia. Irreversible brain damage and progressive neurological deterioration may occur in untreated or late diagnosed patients. Prognosis could be satisfying in the cases with early diagnose and treatment.
Alkaptonuria is a rare autosomal recessive genetic disorder resulting from the deficiency of homogentisate 1,2 dioxygenase (HGD), the third enzyme in the tyrosine degradation pathway. Homogentisic acid produced in excess oxidizes into ochronotic pigment polymer. Accumulation of this pigment in various tissues leads to systemic disease.Clinical, laboratory, molecular findings and treatment characteristics of 35 patients followed up in Ege University Pediatric Nutrition, and Metabolism Department with the diagnosis of alkaptonuria were evaluated retrospectively.Twenty-four males (68.57%) and 11 females (31.42%) with a confirmed diagnosis of alkaptonuria from 32 different families were included in the study. We identified 11 different genetic variants; six of these were novel. c.1033C>T, c.676G>A, c.664G>A, c.731_734del, c.1009G>T, c.859_862delins ATAC were not previously reported in the literature. 24 (68.57%) patients only adhered to a low-protein diet in our study group. Seven (20%) patients initiated a low protein diet and NTBC therapy. Mean urinary HGA decreased by 88.7% with nitisinone. No statistical changes were detected in urinary HGA excretion with the low protein diet group.In our study, alkaptonuria patients were diagnosed at different ages, from infancy to adulthood, and progressed with other systemic involvement in the follow-up. Since the initial period is asymptomatic, giving potentially effective treatment from an early age is under discussion. Raising disease awareness is very important in reducing disease mortality and morbidity rates.
This study was designed to show the role of oxidative stress, nitric oxide and glutathione-related antioxidant enzymes in hypoxia/reoxygenation (H/R)-induced intestinal injury model in mice and to evaluate the potential benefits of arginine and carnitine supplementation.A total of 28 young Balb/c mice were divided into four groups: Group 1 (untreated) was given physiological saline before the experiment; group 2 H/R mice were supplemented with L-arginine; group 3 H/R mice were given L-carnitine for 7 days; and group 4 mice served as controls. At the end of day 7, H/R injury was induced and intestinal tissue malondialdehyde (MDA), nitrate levels and glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) activities were measured.MDA levels were higher in the untreated animals than in the other three groups. MDA levels were higher in the L-arginine-treated animals than in the L-carnitine-treated animals. Nitrate levels were found to be increased in the L-arginine-treated group when compared to the controls. GSH-Px and GR activities were increased in the untreated, the L-arginine and the L-carnitine-treated H/R groups when compared to the control group. GST activities were indifferent between the groups.Oxidative stress contributes to the pathogenesis of H/R-induced intestinal injury. The glutathione redox cycle may have a crucial role in the H/R-induced intestinal injury. L-arginine and L-carnitine supplementations ameliorate the histological evidence of H/R-induced intestinal injury and decrease lipid peroxidation but do not alter the glutathione-related antioxidant enzyme activities.
