Nutritional management in critically ill patients with COVID-19: a retrospective multicentre study.

INTRODUCTION: Although nutritional treatment is an established pillar of multidisciplinary care provided in critical illness, there are many concerns regarding this issue in severe COVID-19. This observational, retrospective, multicentre study aimed to analyse the approach to nutritional treatment among selected intensive care units (ICUs) in Poland. MATERIAL AND METHODS: The medical records of 129 patients hospitalized in five units due to respiratory failure following COVID-19 were analysed in terms of nutritional management on the eighth day of the ICU stay. The Harris-Benedict equation (HB), Mifflin St. Jeor equation (MsJ) and ESPEN formula (20 kcal kg -1 body weight) were used to estimate the energy target for each patient, and two ESPEN formulas determined the protein target (1 g kg -1 body weight and 1.3 g kg -1 body weight). RESULTS: Evaluation of nutritional therapy was performed in 129 subjects. The fulfilment of caloric requirement considering the HB, MsJ and ESPEN formula was 66%, 66.7% and 62.5%, respectively. Two clinical centres managed to provide 70% or more of daily caloric requirements. According to the ESPEN formula, the implementation of the protein target was 70%; however, one of the investigated units provided a median of 157% of the protein demand. The nutritional management varied in the preferred route of nutrition administration. Neither method nor grade of nutrition supply influenced biochemical parameters on the 8th day of ICU stay. CONCLUSIONS: Significant differences in nutritional treatment of critically ill COVID-19 patients in Polish ICUs were noted, which underlines the importance of setting up clear guidelines regarding this issue.

Medical Nutrition Therapy in Critically Ill Patients with COVID-19-A Single-Center Observational Study.

Medical nutrition should be tailored to cover a patient's needs, taking into account medical and organizational possibilities and obstacles. This observational study aimed to assess calories and protein delivery in critically ill patients with COVID-19. The study group comprised 72 subjects hospitalized in the intensive care unit (ICU) during the second and third SARS-CoV-2 waves in Poland. The caloric demand was calculated using the Harris-Benedict equation (HB), the Mifflin-St Jeor equation (MsJ), and the formula recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN). Protein demand was calculated using ESPEN guidelines. Total daily calorie and protein intakes were collected during the first week of the ICU stay. The median coverages of the basal metabolic rate (BMR) during day 4 and day 7 of the ICU stay reached: 72% and 69% (HB), 74% and 76% (MsJ), and 73% and 71% (ESPEN), respectively. The median fulfillment of recommended protein intake was 40% on day 4 and 43% on day 7. The type of respiratory support influenced nutrition delivery. A need for ventilation in the prone position was the main difficulty to guarantee proper nutritional support. Systemic organizational improvement is needed to fulfill nutritional recommendations in this clinical scenario.

Usefulness of Selected Peripheral Blood Counts in Predicting Death in Patients with Severe and Critical COVID-19.

BACKGROUND: Immune dysregulation and hypoxemia are two important pathophysiological problems in patients with COVID-19 that affect peripheral blood count parameters. We hypothesized that assessment of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width index (RDW-SD) could predict death in patients with severe and critical COVID-19. METHODS: Seventy patients admitted to the intensive care unit (ICU) for COVID-19 acute respiratory failure were included in the study. RDW-SD and NLR on the day of ICU admission and peak values during the entire hospitalization were assessed. The primary endpoint was death before ICU discharge. RESULTS: Patients who died had higher NLR on admission (20.3, IQR 15.3-30.2 vs. 11.0, IQR 6.8-16.9; p = 0.003) and higher RDW-SD (48.1 fL; IQR 43.1-50.5 vs. 43.9 fL; IQR 40.9-47.3, p = 0.01) than patients discharged from the ICU. NLR and RDW-SD values on ICU admission accurately predicted death in 76% (AUC = 0.76; 95%CI 0.65-0.86; p = 0.001; cut-off > 14.38) and 72% of cases (AUC = 0.72; 95%CI 0.60-0.82; p = 0.003; cut-off > 44.7 fL), respectively. Multivariable analysis confirmed that NLR > 14.38 on the day of ICU admission was associated with a 12-fold increased risk of death (logOR 12.43; 95%CI 1.61-96.29, p = 0.02), independent of other blood counts, clinical and demographic parameters. CONCLUSIONS: Neutrophil-lymphocyte ratio determined on the day of ICU admission may be a useful biomarker predicting death in patients with severe and critical COVID-19.

Transcription Factor ChREBP Mediates High Glucose-Evoked Increase in HIF-1α Content in Epithelial Cells of Renal Proximal Tubules.

Hyperglycemia/diabetes appears to be accompanied by the state of hypoxia, which especially affects kidneys. The aim of the study was to elucidate the mechanism of high glucose action on HIF-1α expression in renal proximal tubule epithelial cells. The research hypotheses included: (1) the participation of transcription factor ChREBP; and (2) the involvement of the effects resulting from pseudohypoxia, i.e., lowered intracellular NAD+/NADH ratio. The experiments were performed on HK-2 cells and primary cells: D-RPTEC (Diseased Human Renal Proximal Tubule Epithelial Cells-Diabetes Type II) and RPTEC (Renal Proximal Tubule Epithelial Cells). Protein and mRNA contents were determined by Western blot and RT-qPCR, respectively. ChREBP binding to DNA was detected applying chromatin immunoprecipitation, followed by RT-qPCR. Gene knockdown was performed using siRNA. Sirtuin activity and NAD+/NADH ratio were measured with commercially available kits. It was found that high glucose in HK-2 cells incubated under normoxic conditions: (1) activated transcription of HIF-1 target genes, elevated HIF-1α and ChREBP content, and increased the efficacy of ChREBP binding to promoter region of HIF1A gene; and (2), although it lowered NAD+/NADH ratio, it affected neither sirtuin activity nor HIF-1α acetylation level. The stimulatory effect of high glucose on HIF-1α expression was not observed upon the knockdown of ChREBP encoding gene. Experiments on RPTEC and D-RPTEC cells demonstrated that HIF-1α content in diabetic proximal tubular cells was lower than that in normal ones but remained high glucose-sensitive, and the latter phenomenon was mediated by ChREBP. Thus, it is concluded that the mechanism of high glucose-evoked increase in HIF-1α content in renal proximal tubule endothelial cells involves activation of ChREBP, indirectly capable of HIF1A gene up-regulation.

Difficulties in the diagnostics of chronic hyponatremia based on the case study of a 66-year old female patient during antihypertensive therapy.

Clinical consequences of hyponatremia might be serious. It is often related to the administration of diuretics, especially thiazide and thiazide-like diuretics. It is known that elderly subjects are prone to thiazide induced hyponatremia (TIH). A CASE REPORT: A 66-year old female patient was admitted to our Department. The aim of the admission was to complete a differential diagnosis of chronic hyponatremia. For about two years the patient had suffered from the following symptoms: severe headaches, fatigue, episodic mental confusions, stomachaches, and diarrhea. Before admission to the hospital, the patient was treated with bisoprolol, amlodipine, telmisartan, indapamide, furosemide, acetylsalicylic acid, thiamazole, and zolpidem. The general clinical picture might suggest that the cause of hyponatremia was the indapamide diuretic therapy. However, only moderate hyponatremia, normokalemia, as well as, an increased antidiuretic hormone serum concentration were observed. These findings are not typical for TIH. Despite those findings, natremia improved after the cessation of indapamide therapy. CONCLUSIONS: This case report described the atypical presentation of TIH resembling SIADH. TIH diagnosis should be primarily based on the improvement of hyponatremia after the termination of thiazide or thiazide-like diuretic treatment.

Transcription factor ChREBP ­ the coordinator of carbohydrate and lipid metabolism / Czynnik transkrypcyjny ChREBP ­ koordynator metabolizmu weglowodanów i lipidów.

Transcription factor ChREBP, in complex with MLX, binds to carbohydrate-response element (ChoRE) located in the promoters of genes related to glycolysis, gluconeogenesis, pentosephosphate pathway and lipogenesis, activating their transcription following stimulation with glucose, insulin-independently. In this article the mechanisms of ChREBP regulation and ChREBP functions under both physiological and pathophysiological conditions are described in detail. The possible use of ChREBP activity modulation as a therapeutic tool, e.g. in case of nonalcoholic fatty liver disease, diabetes type 2 and cancers, is also discussed.

Ni/cerium Molybdenum Oxide Hydrate Microflakes Composite Coatings Electrodeposited From Choline Chloride: Ethylene Glycol Deep Eutectic Solvent.

Cerium molybdenum oxide hydrate microflakes are codeposited with nickel from a deep eutectic solvent-based bath. During seven days of exposure in 0.05 M NaCl solution, the corrosion resistance of composite coating (Ni/CeMoOxide) is slightly reduced, due to the existence of some microcracks caused by large microflakes. Multielemental analysis of the solution, in which coatings are exposed and the qualitative changes in the surface chemistry (XPS) show selective etching molybdenum from microflakes. The amount of various molybdenum species within the surface of coating nearly completely disappear, due to the corrosion process. Significant amounts of Ce3+ compounds are removed, however the corrosion process is less selective towards the cerium, and the overall cerium chemistry remains unchanged. Initially, blank Ni coatings are covered by NiO and Ni(OH)2 in an atomic ratio of 1:2. After exposure, the amount of Ni(OH)2 increases in relation to NiO (ratio 1:3). For the composite coating, the atomic ratios of both forms of nickel vary from 1:0.8 to 1:1.3. Despite achieving lower corrosion resistance of the composite coating, the applied concept of using micro-flakes, whose skeleton is a system of Ce(III) species and active form are molybdate ions, may be interesting for applications in materials with potential self-healing properties.

Hypoxia increases the rate of renal gluconeogenesis via hypoxia-inducible factor-1-dependent activation of phosphoenolpyruvate carboxykinase expression.

Although up to 25% of glucose released into circulation in the postabsorptive state comes from renal gluconeogenesis, the regulatory mechanisms of this process are still poorly recognized, comparing to hepatic ones. The aim of the present study was to examine if hypoxia-inducible factor-1 (HIF-1) might be involved in the regulation of glucose de novo synthesis in kidneys. It was found that HK-2 cells (immortalized human kidney proximal tubules, capable of gluconeogenesis/glycogen synthesis) cultured with gluconeogenic substrates either in hypoxia (1% O2) or in the presence of DMOG (an inhibitor of HIF-1α degradation) exhibited increased glycogen content. This phenomenon was not correlated with augmented glucose intake and the effects were reversed by echinomycin (an inhibitor of HIF-1 binding to HRE sequence). As concluded from the measurement of the intracellular content of gluconeogenic intermediates followed by Western blot analysis, under conditions of hypoxia/increased HIF-1 level the activity of phosphoenolpyruvate carboxykinase (PEPCK) was elevated, as a result of increased expression of the cytosolic isoform of PEPCK (PEPCK-C). Chromatin immunoprecipitation (ChIP) analysis proved HIF-1 ability to bind to the promoter region of PEPCK-C gene. The final conclusion that hypoxia/HIF-1 accelerates the rate of renal glucogenesis via the mechanism engaging activation of PEPCK-C expression might be useful in terms of e.g. diabetes treatment, as it is commonly accepted that under diabetic conditions kidneys and liver seem to be equally important sources of glucose synthesized de novo.

Melatonin Lowers HIF-1α Content in Human Proximal Tubular Cells (HK-2) Due to Preventing Its Deacetylation by Sirtuin 1.

Although melatonin is widely known for its nephroprotective properties, there are no reports clearly pointing at its impact on the activity of hypoxia-inducible factor-1 (HIF-1), the main mediator of metabolic responses to hypoxia, in kidneys. The aim of the present study was to elucidate how melatonin affects the expression of the regulatory subunit HIF-1α in renal proximal tubules. HK-2 cells, immortalized human proximal tubular cells, were cultured under hypoxic conditions (1% O2). Melatonin was applied at 100 µM concentration. Protein and mRNA contents were determined by Western blot and RT-qPCR, respectively. HIF-1α acetylation level was established by means of immunoprecipitation followed by Western blot. Melatonin receptors MT1 and MT2 localization in HK-2 cells was visualized using immunofluorescence confocal analysis. It was found that melatonin in HK-2 cells (1) lowered HIF-1α protein, but not mRNA, content; (2) attenuated expression of HIF-1 target genes; (3) increased HIF-1α acetylation level; and (4) diminished sirtuin 1 expression (both protein and mRNA). Sirtuin 1 involvement in the regulation of HIF-1α level was confirmed applying cells with silenced Sirt1 gene. Moreover, the presence of membrane MT1 and MT2 receptors was identified in HK-2 cells and their ligand, ramelteon, turned out to mimic melatonin action on both HIF-1α and sirtuin 1 levels. Thus, it is concluded that the mechanism of melatonin-evoked decline in HIF-1α content in renal proximal tubular cells involves increased acetylation of this subunit which results from the attenuated expression of sirtuin 1, an enzyme reported to deacetylate HIF-1α. This observation provides a new insight to the understanding of melatonin action in kidneys.

[Sirtuins and their role in metabolism regulation]. / Sirtuiny i ich rola w regulacji metabolizmu.

Sirtuins are - in mammals - a family of seven enzymes (sirtuin 1-7) involved in post-translational modification of proteins (mainly deacetylation, but also: polyADP-ribosylation, demalonylation or lipoamidation), and thus - in the regulation of many metabolic processes. The activity of all sirtuins depends on the availability of NAD+. However, the function of individual isoforms is different, even mutually antagonistic. In this article the role of sirtuins in the regulation of glucose and lipid metabolism and in DNA repair mechanisms is described in detail. The significance of these enzymes in diseases pathogenesis, with particular emphasis on diabetes and cancer, is also discussed, indicating the possible therapeutic use of sirtuin activity modulators.

An Analysis of the Association between Epilepsy-Related Genes and Vertigo in the Polish Population.

Considering the possibility of a common genetic background of vertigo and epilepsy, we genotyped an affected group of individuals with vertigo and an unaffected group, by studying 26 single-nucleotide polymorphisms (SNPs) in 14 genes which were previously reported to be of particular importance for epilepsy. Significant differences were found between the patients and the control group (χ2 = 38.3, df = 3, p = 1.6 × 10-7) for the frequencies of haplotypes consist ing of 2 SNPs located in chromosome 11 (rs1939012 and rs1783901 within genes MMP8 and SCN3B, respectively). The haplotype rs1939012:C-rs1783901:A, consisting of the minor-frequency alleles was found to be associated with a higher risk of vertigo (OR = 5.0143, 95% CI = 1.6991-14.7980, p = 0.0035). In contrast, the haplotype rs1939012:T-rs1783901:A showed a significant association with a decreased risk of the disease (OR = 0.0597, 95% CI = 0.0136-0.2620, p = 0.0002). Our results suggest that the SNPs rs1939012 and rs1783901 may play a potential role of gene regulation and/or epistasis in a complex etiology of vertigo.

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes.

Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level.

ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has delivered some new insights into the recently discussed issue of the usefulness of Nox inhibition as a potential antidiabetic strategy.

NADPH oxidase inhibitor, apocynin, improves renal glutathione status in Zucker diabetic fatty rats: a comparison with melatonin.

Apocynin (4'-hydroxy-3'-methoxyacetophenone) is the most commonly used NADPH oxidase (Nox) inhibitor. However, its application raises serious controversies, as the compound has been reported to reveal some prooxidative effects. The aim of this study was to elucidate apocynin action on glutathione, the main intracellular antioxidant, metabolism in kidneys of Zucker diabetic fatty (ZDF) rat, a well established model of diabetes type 2. Additionally, apocynin effects were compared with those of melatonin. The experiments were performed on five groups of animals: (1) untreated lean (?/+) ZDF rats, (2) ZDF ?/+ rats treated with apocynin (2 g/l) in drinking water, (3) untreated obese diabetic (fa/fa) ZDF rats, (4) ZDF fa/fa rats treated with apocynin (2 g/l) in drinking water, and (5) ZDF fa/fa rats treated with melatonin (20 mg/l) in drinking water. After 8weeks of the treatment, the following parameters were measured in kidneys: NADPH oxidase activity, the rate of hydroxyl free radicals (HFR) production, GSH and GSSG content and the activities of the enzymes of glutathione metabolism: γ-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione peroxidase (GPx). Compared to ?/+ controls, ZDF fa/fa rats exhibited increased Nox activity, accelerated HFR generation and dramatically lowered GSH/GSSG ratio accompanied by increased GPx and diminished GCS activities. In case of diabetic animals, apocynin treatment resulted in attenuation of both Nox activity and HFR production, restoration of control GSH/GSSG ratio (due to both an increase in GSH and a decline in GSSG content), normalization of GPx activity and a slight increase in GCS activity. Similar observations were made upon melatonin application to ZDF fa/fa rats. Thus, it is concluded that, in the diabetic model studied, apocynin extends a beneficial effect on renal glutathione homeostasis. The mechanism of this phenomenon involves attenuation of glutathione peroxidase activity, which is overstimulated under conditions of oxidative stress accompanying diabetes.

Inhibition of renal gluconeogenesis contributes to hypoglycaemic action of NADPH oxidase inhibitor, apocynin.

NADPH oxidase, catalysing superoxide radical (O2(.-)) formation, is considered as a main source of reactive oxygen species in kidneys and its increased activity is supposed to be involved in the development of diabetic nephropathy. The aim of this study was to investigate the effect of NADPH oxidase inhibitor, apocynin, on renal gluconeogenesis, which is an important source of endogenous glucose under diabetic conditions. The following observations were made during the experiments performed on isolated renal proximal tubules of control and alloxan diabetic rabbits: (1) apocynin (200 µM) inhibited the rate of glucose synthesis by 45-80%, depending on the substrate applied; (2) the rate of glucose production was also significantly diminished in the presence of TEMPOL (5mM), a superoxide radical scavenger, suggesting that the decrease in O2(.-) formation might be involved in apocynin-evoked gluconeogenesis inhibition; (3) the activities of phosphoenolpyruvate carboxykinase (PEPCK) and/or aldolase were lowered in the presence of either apocynin or TEMPOL, as concluded from the intracellular levels of gluconeogenic intermediates. The data from in vivo experiments indicated that apocynin treatment (2g/l of drinking water): (1) significantly (by about 30%) attenuated serum glucose concentration in diabetic rabbits and did not affect glycaemia in control animals; (2) normalized diabetes-stimulated rate of glucose synthesis and slightly inhibited gluconeogenesis in control rabbits; (3) normalized diabetes-increased activity of mitochondrial PEPCK and lowered cytosolic PEPCK activity by about 20% below the value for untreated control animals; (4) slightly decreased the activity of mitochondrial PEPCK and did not change the activity of cytosolic one in control rabbits. Thus, it is concluded that: (1) the inhibition of NADPH oxidase might contribute to lowered rate of renal gluconeogenesis, probably due to decreasing PEPCK activity; (2) inhibition of renal gluconeogenesis is involved in apocynin hypoglycaemic action in vivo; (3) apocynin might be beneficial for diabetes treatment.

Differential action of methylselenocysteine in control and alloxan-diabetic rabbits.

Antidiabetic action of inorganic selenium compounds is commonly accepted. Since in diet selenium mainly exists as selenoamino acids, potential hypoglycemic properties of methylselenocysteine (MSC) were investigated in four groups of rabbits: untreated and MSC-treated control animals as well as alloxan-diabetic and MSC-treated diabetic rabbits. MSC (at a dose of 1mg/kg body weight) was administered daily for 3 weeks via intraperitoneal injection. The data show, that in MSC-treated control animals plasma glucose concentration was diminished, while plasma urea and creatinine levels as well as urine albumin content were elevated and necrotic changes occurred in kidney-cortex. Decreased GSH/GSSG ratios in blood, liver and kidney-cortex were accompanied by increased glutathione peroxidase and glutathione reductase activities and a diminished renal gamma-glutamylcysteine synthetase activity. Death of 50% of control animals was preceded by a dramatic decline in blood glucose concentration. Surprisingly, in MSC-treated diabetic rabbits, plasma glucose levels were either normalized or significantly decreased. Blood and liver GSH/GSSG ratios were increased and renal functions were markedly improved, as indicated by a diminished albuminuria and attenuated histological changes characteristic of diabetes. However, after administration of MSC to diabetic rabbits plasma urea and creatinine levels as well as renal GSH/GSSG ratios were not altered. In view of MSC-induced marked accumulation of selenium in kidneys and liver of control rabbits, accompanied by a decline in blood glucose level, disturbance of glutathione homeostasis and kidney-injury, application of MSC in chemotherapy needs a careful evaluation. On the contrary, MSC supplementation might be beneficial for diabetes therapy due to an improvement of both glycemia and renal function.

Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits.

The therapeutic potential of taurine was investigated under diabetic conditions. Alloxan diabetic rabbits were treated daily for three weeks with 1% taurine in drinking water. The following parameters were measured: 1) serum glucose, urea, creatinine and hydroxyl free radical (HFR) levels; 2) blood glutathione redox state; 3) urine albumin concentration; 4) hepatic and renal HFR levels, GSH/GSSG ratios and the activities of catalase, superoxide dismutase and the enzymes of glutathione metabolism; 5) renal NADPH oxidase activity; 6) the rates of renal and hepatic gluconeogenesis. Histological studies of kidneys were also performed. Taurine administration to diabetic rabbits resulted in 30% decrease in serum glucose level and the normalisation of diabetes-elevated rate of renal gluconeogenesis. It also decreased serum urea and creatinine concentrations, attenuated diabetes-evoked decline in GSH/GSSG ratio and abolished hydroxyl free radicals accumulation in serum, liver and kidney cortex. Animals treated with taurine exhibited elevated activities of hepatic gamma-glutamylcysteine syntetase and renal glutathione reductase and catalase. Moreover, taurine treatment evoked the normalisation of diabetes-stimulated activity of renal NADPH oxidase and attenuated both albuminuria and glomerulopathy characteristic of diabetes. In view of these data, it is concluded that: 1) diminished rate of renal gluconeogenesis seems to contribute to hypoglycaemic effect of taurine; 2) taurine-induced increase in the activities of catalase and the enzymes of glutathione metabolism is of importance for antioxidative action of this amino acid and 3) taurine nephroprotective properties might result from diminished renal NADPH oxidase activity. Thus, taurine seems to be beneficial for the therapy of both diabetes and diabetic nephropathy.

[Taurine and its potential therapeutic application]. / Tauryna i jej potencjalne wykorzystanie w terapii.

Taurine (2-aminoethylsulphonic acid), a non-protein amino acid, is present in most animal tissues. Its highest concentrations are found in skeletal muscles, heart, brain, and retina. Although this compound can be synthesized from other sulfonic amino acids such as methionine and cysteine, the endogenous production is insufficient for the human organism, so taurine has to be delivered with food. Animal products such as fish, meat, and milk are good sources of taurine. Taurine exhibits antioxidative properties, regulates intracellular Ca2+ concentration, acts as a neuromediator and neuromodulator, is responsible for osmoregulation, is involved in cholic acid production, and modulates inflammatory reactions. The amino acid seems to be an important trophic factor in the retina, nervous system, and kidneys. The protective action of taurine on heart muscle and the antagonistic effects of this amino acid and angiotensin II arouse great interest. The role of taurine in glucose metabolism regulation is also extensively studied. However, the detailed mechanisms of taurine's action are still unknown. Lowered tissue taurine concentrations are characteristic of many pathological states, including diabetes. In many studies, also in clinical trials, it has been reported that supplementation with taurine reverses or at least attenuates pathological changes. Therefore, it seems likely that taurine might be used in the treatment of cardiomyopathy, myotony, hypercholesterolemia, or diabetes. However, future thorough studies are required.