Grażyna Dutkiewicz

Death caused by addictive inhalation of nitrous oxide.

Intoxications with nitrous oxide have been, and still are, a rarity in forensic medicine. Apart from accidental overdose during hospital procedures, intoxication with this gas is the result of voluntary inhalation. We report the fatal case of a 32-year-old male who died during inhalation of nitrous oxide from whipped dairy cream cans and hint on the role of the internet in creating new behaviors among drug addicts. We rely on the autopsy report from the Department of Forensic Medicine, Pomeranian Medical University in Szczecin, on laboratory tests, and court files. Neither the autopsy nor the toxicologic and histopathologic tests disclosed the exact cause of death. However, circumstances in which the body was discovered were indicative that death resulted from cardiorespiratory failure. The present case is interesting with regard to its rarity, diagnostic difficulties and potential harm from nitrous oxide used by the food industry.

Polymorphisms of superoxide dismutase, glutathione peroxidase and catalase genes in patients with post-transplant diabetes mellitus.

BACKGROUND AND AIMS Post-transplant diabetes mellitus (PTDM) is a metabolic disorder that develops in response to a relative insulin deficiency in patients after organ transplantation treated with immunosuppressive drugs. Several studies have suggested that oxidative stress may be associated with diabetes and its complications. The aim of this study was to examine the association of polymorphisms in superoxide dismutase, catalase and glutathione peroxidase genes with PTDM in patients after kidney transplantation. METHODS The study included 159 patients receiving kidney transplants. PTDM was diagnosed in 21 patients. RESULTS Analyzing the C599T (Pro200Leu) polymorphism in the GPX1 gene PTDM was diagnosed in 8.45% of patients with CC genotype, 13.43% with CT and in 28.57% with TT. Allele T was significantly more frequent among patients with PTDM compared to patients without PTDM (OR = 2.14, 95% CI = 1.11-4.12, p = 0.024). There were no associations between SOD1, SOD2 and CAT polymorphisms and PTDM. CONCLUSIONS The present results suggest that Pro200Leu polymorphism of the GPX1 gene may be associated with the risk of PTDM development in renal graft recipients.

Chlorpropamide Toxicity with Survival Despite 27-Day Hypoglycemia

CASE REPORT In the past 5 years at our institution, 12 cases involving the ingestion of chlorpropamide 3-15 g were fatal. We report a 23-year-old woman with an estimated ingestion of chlorpropamide 5-10 g. Initial cardiovascular collapse, attributed to the blockade of potassium channel transport, responded to intensive support including 3 days of cardiac pacing. Urinary excretion of chlorpropamide and hypoglycemia persisted until day 27. The toxic mechanisms and high risk of chlorpropamide are summarized. A fatal therapeutic dose ratio as low as 4:1 has made this antidiabetic agent obsolete.

Copper modifies the activity of sodium-transporting systems in erythrocyte membrane in patients with essential hypertension.

The aim of the study was to verify the hypothesis if copper could influence the activity of sodium-transporting systems in erythrocyte membrane that could be related to essential hypertension. The examined group of patients consisted of 15 men with hypertension. The control group was 11 healthy male volunteers. The Na+/H+ exchanger (NHE) activity in erythrocytes was determined according to Orlov et al. The activity of transporting systems (ATP-Na+/K+; co-Na+/K+/Cl−; ex-Na+/Li+; free Na+ and K+ outflow [Na+, K+-outflow]) was determined according to Garays method. The concentration of copper in plasma was assessed using atomic absorption spectrometry. The activity of ATP-Na+/K+ (μmol/L red blood cells [RBCs]/h) in hypertensive patients was 2231.5±657.6 vs 1750.5±291 in the control (p<0.05), the activity of co-Na+/K+/Cl− (μmol/L RBCs/h) in hypertensives was 171.3±77.9 vs 150.7±53.9 in the control (NS). Na+-outflow (μmol/L RBCs/h) in hypertensives was 118.3±51.6 vs 113.3±24.4 in the control (NS). The K+-outflow (μmol/L RBCs/h) in hypertensives was 1361.7±545.4 vs 1035.6±188.3 in the control (NS). The activity of ex-Na+/Li+ (μmol/L RBCs/h) in hypertensive patients was 266.1±76.1 vs 204.1±71.6 in the control (p<0.05). NHE activity (mmol/L RBCs/h) in hypertensives was 9.7±2.96 vs 7.7±1.33 in the control (p<0.05). In hypertensive patients, negative correlation was found between the activity of Na+/K+/Cl− co-transport and plasma copper concentration (Rs=−0.579, p <0.05) and between the activity of ex-Na+/Li+ and plasma copper concentration (Rs=−0.508, p<0.05). Plasma copper concentration significantly influences the activity of sodium transporting systems in erythrocyte membrane. Copper supplementation could be expected to provide therapeutic benefits for hypertensive patients.

Autosomal dominant polycystic kidney disease and hypertension are associated with left ventricular mass in a gender-dependent manner.

Background: The aim of this study was to compare echocardiographic parameters in patients with autosomal dominant polycystic kidney disease (ADPKD) and in controls with normal kidney function taking into account gender and the presence of hypertension. Methods: 47 patients with ADPKD (age 36.3 ± 11.0 years) and 49 healthy controls (36.8 ± 9.2 years) were enrolled. M-mode echocardiography was performed in all subjects. Left ventricular hypertrophy (LVH) was diagnosed when the left ventricular mass index (LVMI) was greater than or equal to 125 g/m2 in males and 110 g/m2 in females. Results: The prevalence of LVH was greater in ADPKD patients than in controls (13% vs 2%; p=0.05). Among females, ADPKD patients demonstrated greater LVMI (87.9 ± 18.5 vs 68.8 ± 15 g/m2, p=0.00009) than controls. There was a positive correlation between LVMI and blood pressure in ADPKD females (Rs=0.54, p=0.027 for systole blood pressure-SBP and Rs=0.50, p=0.0053 for diastole blood pressure-DBP) but not in males. Conclusion: Left ventricular mass is increased in ADPKD females with normal renal function. A positive correlation between SBP and DBP and LVMI was found in ADPKD females but not in ADPKD males.

The association between eNOS intron 4 VNTR polymorphism and delayed graft function of kidney allografts

Dutkiewicz G, Domanski L, Binczak‐Kuleta A, Pawlik A, Safranow K, Ciechanowicz A, Dziedziejko V, Ciechanowski K. The association between eNOS intron 4 VNTR polymorphism and delayed graft function of kidney allografts.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01187.x
© 2009 John Wiley & Sons A/S.

Lack of association of polymorphisms 239+34A/C in the SOD1 gene and 47C/T in the SOD2 gene with delayed graft function and acute and chronic rejection of kidney allografts.

The superoxide dismutases (SODs) seem to be the most important enzymes involved in defense against reactive oxygen species, in particular against superoxide anion radicals. We hypothesized that genetic variability of antioxidant enzymes may have a role in development of these complications. The objective of the present study was to examine the association between polymorphisms 239+34A/C in the SOD1 gene or 47C/T in the SOD2 gene and development of delayed graft function (DGF) and acute or chronic rejection. The study included 187 recipients of first renal transplants. Patient history was analyzed taking into account DGF, acute rejection episodes, and chronic rejection. The polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant associations between the polymorphisms and DGF or acute or chronic rejection. Our findings suggest that polymorphisms in SOD1 and SOD2 are not associated with development of either DGF or acute or chronic rejection.

The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis

Abstract Background: Patients on long-term hemodialysis frequently suffer from complications, such as secondary hyperparathyroidism, bone fractures, and arteriosclerosis. The process of regulating Ca/P metabolism depends on factors, such as FGF23 and Klotho. This study aimed to answer the question of whether the Klotho polymorphism rs9536314 is associated with FGF23 plasma concentration. Methods: In 118 patients undergoing hemodialysis, blood was collected before and after hemodialysis. The following parameters were measured in plasma: FGF23, serum: Ca, P, PTH, HGB, and iron concentrations. The KL gene polymorphism rs9536314 was identified by PCR-RFLP. Results: The KL polymorphism rs9536314 was not associated with Ca, P, PTH, or FGF23. There was a negative correlation between FGF23 and blood HGB levels and positive correlation between FGF23 and ESA dose. Conclusions: The results obtained may indicate that there is no association between the KL polymorphism and FGF23 concentration in patients undergoing long-term.

The association of –262C/T polymorphism in the catalase gene and delayed graft function of kidney allografts

Background:  Catalase is an intracellular antioxidant enzyme that is mainly located in cellular peroxisomes and in the cytosol. This enzyme plays a significant role in the development of tolerance to oxidative stress in the adaptive response of cells and tissues. The aim of the present study was to examine the association between the –262C/T polymorphism in the catalase gene and delayed graft function (DGF), acute rejection and chronic allograft nephropathy of kidney allografts.

Brain-derived neurotrophic factor: a new face of metabolic disorders.

Insulin resistance is a disorder of glucose homeostasis manifested by reduced sensitivity of muscles, adipose tissue and liver to insulin. Its aetiology is well understood and encompasses the polymetabolic syndrome, obesity, limited physical activity, endocrine pathology (polycystic ovary syndrome), chronic kidney disease and hereditary defects. Research continues to provide new information on the pathology and causes of insulin resistance while recent reports have focused on associations between the nervous system and metabolic disorders. It appears that the nervous system is involved in metabolic processes through production of specific compounds called neurotrophins. Thomas Willis, who noted that diabetes is often seen in patients with a stressful lifestyle, published the first work in this direction 400 years ago. In 1935, W Menninger, an American psychiatrist described what he called the diabetic personality. Today, there is little doubt that the nervous system and insulin metabolism are interrelated. Brain-derived neurotropic factor (BDNF) belongs to the neurotrophin family which regulates processes of growth and survival of neurons. The first reports on BDNF have concentrated on its role in learning and memory. Involvement of BDNF in diseases of the nervous system (Alzheimer’s disease, depression) has been demonstrated. The study of Nitta et al. showed that BDNF plays a pathogenic role in synaptic dysfunction in type 2 diabetes. BDNF acts on the tyrosine-related kinase B (TrkB) receptor present in the central nervous system (CNS), hypothalamus and in some other organs. Studies in animals have revealed that BDNF penetrates the blood–brain barrier. Progression of obesity, diabetes and cardiovascular diseases may be modified by induction or inhibition of BDNF inside and outside of the CNS. The sympathetic system has nerve endings in the white and brown adipose tissue through which it regulates energy output. This process is mediated by noradrenaline and controlled by BDNF. Genetic studies have shown that deletion of the BDNF gene is lethal in homozygotes but produces increased appetite, obesity and diabetes in heterozygotes. In animals, administration of BDNF into the CNS or subcutaneously modulates the central and peripheral nervous system. It has been shown that BDNF reduces food intake and lowers blood glucose concentration in genetically modified (db/db) obese mice. These mutants suffer from obesity, hyperinsulinaemia, hyperleptinaemia and hyperactivity. Administration of BDNF led to a decrease in food intake and had beneficial effects on glucose homeostasis and improved insulin resistance. Expression of BDNF in the hypothalamus activates the sympathetic system manifested with hypertrophy of the brown adipose tissue. Research in patients with type 2 diabetes has revealed significantly lower plasma BDNF concentrations which correlated with body mass index, high-density lipoprotein cholesterol and triglyceride concentrations. Regulation of cholesterol metabolism in the CNS neurons remains ill defined. Suzuki et al. investigated the effect of BDNF on the biosynthesis of cholesterol in cultured CNS neurons. The results suggested that BDNF regulates cholesterol biosynthesis for the development of presynaptic function. In another study it has been observed that a high fat diet impairs hippocampal neurogenesis through increased lipid peroxidation and increased lipid oxidation. Nevertheless, debate continues on the relationship between BDNF and obesity. Reduced plasma concentrations of BDNF have been found in patients with type 2 diabetes regardless of obesity. Moreover, there was an inverse correlation between BDNF and fasting glucose concentrations in this study. No correlation with insulin was found and BDNF gene polymorphism analysis has not revealed any associations with diabetes or obesity. Hyperglyacaemic and euglycaemic clamp studies in healthy individuals have demonstrated that BDNF release in the CNS is blocked only by hyperglycaemia. On the other hand, elevated concentrations of BDNF were observed in obese patients with type 2 diabetes. Physical activity not only increases BDNF concentrations, but also improves memory and insulin sensitivity of tissues. There is evidence that insulin participates in cognitive and memory processes through receptors in the CNS. Impaired glucose tolerance has a negative impact on memory and on the function of the hippocampus where concentrations of BDNF are normally high.