Tubular kidney function in patients with type 2 Diabetes mellitus, microalbuminuria and proteinuria

Introduction: Diabetes melitus (DM) and hypertension are the most frequent causes of kidney function damage. Many different tests are developed to detect reversible functional kidney changes (detection of microalbuminuria and selective urinary enzymes). Objective The aim of our study was to examine tubular kidney function in type 2 DM patients with different proteinuria levels, and to compare these results with healthy people. Method The patients with type 2 DM and creatinine clearance >80 ml/min were included in the study. According to the levels of proteinuria, the patients were classified in three groups: group I - patients with proteinuria <300 mg/24 h, and no microalbuminuria; group II - the patients with proteinuria <300 mg/24 h and microalbuminuria >20 mg/24 h; and group III- the patients with proteinuria >300 mg/24 h. The control group consisted of healthy subjects. Results The study revealed that in type 2 DM patients and normal global kidney function, fractional excretions of sodium, potassium, and phosphates as well as renal phosphate concentrations were not adequately sensitive markers to detect damage in tubular kidney function in DM. There were some changes of urate fractional excretion in these patients: this value was significantly lower in patients with microalbuminuria compared with those with proteinuria >300 mg/24 h, as well as in the control group (p<0.05). Hormone dependent tubular kidney activity, urinary osmolarity, and urea fractional excretion in all patients were within normal ranges. Conclusion It is evident that routine laboratory analyses are not sensitive markers to detect early changes of kidney function in type 2 DM

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Background: Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. Methods: We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brain-barrier (BBB). Results: Serum UA concentrations were found to be significantly lower in MS patients compared with controls (p=0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (p=0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (p=0.043), but not in controls. Conclusions: Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage of UA molecules from serum through the damaged BBB and the balance between consumption/production within the central nervous system (CNS). Clin Chem Lab Med 2009;47:848–53.Peer Reviewe

Genetic and Environmental Dispositions for Cardiovascular Variability: A Pilot Study

Background: The aim of our study was to evaluate the degree of genetic homozygosity in the group of patients with coronary artery disease (CAD), as well as to evaluate morphogenetic variability in CAD patients regarding the presence of investigated risk factors (RF) compared to a control sample of individuals. Additionally, we aimed to evaluate the distribution of ABO blood type frequencies between tested samples of individuals. Methods: This study analyzed individual phenotype and morphogenetic variability of 17 homozygously-recessive characteristics (HRC), by using HRC test in a sample of 148 individuals in CAD patients group and 156 individuals in the control group. The following RF were analyzed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. Results: The mean value of HRC in CAD patients is significantly higher, while variability decreases compared to the control sample (CAD patients: 4.24 ± 1.59, control sample: 3.75 ± 1.69; VCAD-patients = 37.50%, VC = 45.07%). There is a significant difference in individual variations of 17 HRC between control sample and CAD patients (χ2 = 169.144; p < 0.01), which points out to different variability for tested genes. Mean values of HRC significantly differed in CAD patients in regard to the number of RF present. A blood type (OR = 1.75) is significant predictor for CAD, while O blood type (OR = 0.43) was significantly associated with controls. Conclusion: There is a higher degree of recessive homozygosity in CAD patients versus individuals in the control sample, and the presence of significant variations in the degree of recessive homozygosity as the number of tested RF increases

The Gender Impact on Morphogenetic Variability in Coronary Artery Disease: A Preliminary Study

We analyzed morphogenetic variability and degree of genetic homozygosity in male and female individuals with coronary artery disease (CAD) versus unaffected controls. We have tested 235 CAD patients; 109 were diagnosed also with diabetes mellitus (DM) and 126 with hypertension (HTN). We additionally evaluated 152 healthy individuals without manifested CAD. For the evaluation of the degree of recessive homozygosity, we have performed the homozygously recessive characteristics (HRC) test and tested 19 HRCs. In controls, the frequency of HRC for males was 2.88 ± 1.89, while for females, it was 3.65 ± 1.60. In the CAD group, the frequency of HRC for males was 4.21 ± 1.47, while for females, it was 4.73 ± 1.60. There is significant difference in HRC frequencies between controls and CAD separately for males (p < 0.001) and females (p < 0.001). The same applies between controls and CAD with DM (males: p < 0.001 and females: p = 0.004), and controls and CAD with HTN (males: p < 0.001 and females: p < 0.001). There is no significant difference in HRC frequencies between the group of CAD with DM and the group of CAD with HTN (males: p = 0.952 and females: p = 0.529). Our findings point to the increased degree of recessive homozygosity and decreased variability in both genders of CAD patients versus controls, indicating the potential genetic predisposition for CAD

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

Hyperhomocysteinemia (HHC), both basal and after methionine load, may occur due to genetic disorders or deficiencies of nutrients that affect the remethylation or trans-sulphuration pathways during methionine metabolism. HHC is involved in the pathogenesis of many illnesses as a result of its prooxidative effect and its impairment of antioxidative protection. The aim was to examine the effects of subchronic methionine overload on the body weight and standard biochemical parameters in rat serum and to examine whether simultaneous subchronic intraperotoneal administration of methionine alone or together with L-cysteine or N-acetyl-cysteine resulted in a change in the body weight and biochemical parameters in the rat serum. The research was conducted during a three-week period (male Wistar albino rats, n=36, body weight of approximately 160 g, age of 15-20 days), and the animals were divided into a control group and three experimental groups of 8-10 animals each: a) control group (0.9% sodium chloride 0.1-0.2 ml/day); b) methionine (0.8 mmol/kg/bw/day) (MET group); c) methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (L-cys+MET group); and d) methionine (0.8 mmol/kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (NAC+MET group). In addition to the body weight monitoring, the levels of total homocysteine and the standard biochemical parameters in blood samples (plasma or serum) were determined. The results indicated that monitoring the homocysteine levels and standard biochemical parameters in blood could be used for analysis and could provide an excellent guideline for distinguishing between toxic and non-toxic doses of methionine intake, which may be meaningful for clinical applications