Showing papers by "Gdańsk Medical University published in 2011"

Reappraisal of European guidelines on hypertension management:: A European Society of Hypertension Task Force document

Abstract: ACEangiotensin-converting enzymeBPblood pressureDBPdiastolic blood pressureeGFRestimated glomerular filtration rateESCEuropean Society of CardiologyESHEuropean Society of HypertensionETendothelinIM...

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Abstract: Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: -34/-13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Abstract: Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA) glutamate receptor agonist quinolinic acid (QUIN) in the subgenual anterior cingulate cortex (sACC), anterior midcingulate cortex (aMCC) and pregenual anterior cingulate cortex (pACC) of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5) was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003) and the aMCC (P = 0.015) compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558). Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD. These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies.

Perceptions of appropriateness of care among European and Israeli intensive care unit nurses and physicians.

Abstract: Clinicians in intensive care units (ICUs) who perceive the care they provide as inappropriate experience moral distress and are at risk for burnout. This situation may jeopardize patient quality of care and increase staff turnover.

Cellular redox pathways as a therapeutic target in the treatment of cancer.

Abstract: The vulnerability of some cancer cells to oxidative signals is a therapeutic target for the rational design of new anticancer agents. In addition to their well characterized effects on cell division, many cytotoxic anticancer agents can induce oxidative stress by modulating levels of reactive oxygen species (ROS) such as the superoxide anion radical, hydrogen peroxide and hydroxyl radicals. Tumour cells are particularly sensitive to oxidative stress as they typically have persistently higher levels of ROS than normal cells due to the dysregulation of redox balance that develops in cancer cells in response to increased intracellular production of ROS or depletion of antioxidant proteins. In addition, excess ROS levels potentially contribute to oncogenesis by the mediation of oxidative DNA damage. There are several anticancer agents in development that target cellular redox regulation. The overall cellular redox state is regulated by three systems that modulate cellular redox status by counteracting free radicals and ROS, or by reversing the formation of disulfides; two of these are dependent on glutathione and the third on thioredoxin. Drugs targeting S-glutathionylation have direct anticancer effects via cell signalling pathways and inhibition of DNA repair, and have an impact on a wide range of signalling pathways. Of these agents, NOV-002 and canfosfamide have been assessed in phase III trials, while a number of others are undergoing evaluation in early phase clinical trials. Alternatively, agents including PX-12, dimesna and motexafin gadolinium are being developed to target thioredoxin, which is overexpressed in many human tumours, and this overexpression is associated with aggressive tumour growth and poorer clinical outcomes. Finally, arsenic derivatives have demonstrated antitumour activity including antiproliferative and apoptogenic effects on cancer cells by pro-oxidant mechanisms, and the induction of high levels of oxidative stress and apoptosis by an as yet undefined mechanism. In this article we review anticancer drugs currently in development that target cellular redox activity to treat cancer.

Elastography of the uterine cervix: implications for success of induction of labor

Abstract: Objectives To perform a preliminary investigation into the use of elastography for cervical assessment, in order to determine the effectiveness of this method for the evaluation of cervical consistency. Methods Elastography of the uterine cervix was performed in 29 patients before induction of labor, with tissue surrounding the internal os described using a numeric scale called the elastography index (EI). A color map from purple to red was produced with the hardest tissues displayed as purple and assigned a score of 0 points and progressively softer tissues displayed as blue (1 point), green (2 points), yellow (3 points) and red (4 points). The EI of tissue around the internal os, in the middle part of the cervical canal and around the external os were analyzed in relation to the success of induction of labor using the t-test. Results The mean EI of the internal os in the group of patients with successful induction of labor was 1.23, while in the group with failed induction of labor it was 0.39 (Student's t-test, P = 0.024). No difference was found for the EI of the middle part of the cervical canal or for the EI of the external os in relation to the success of induction of labor (P > 0.05). Conclusion Elastography of the uterine cervix may be an objective method for assessment of softening of tissue in the region of the internal os before induction of labor. Standardization of the cervical properties observed on elastography during pregnancy may help to guide the use of prostaglandins or oxytocin for induction of labor. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial

Abstract: Summary Background TP53 has a crucial role in the DNA damage response. We therefore tested the hypothesis that taxanes confer a greater advantage than do anthracyclines on breast cancers with mutated TP53 than in those with wild-type TP53 . Methods In an open-label, phase 3 study, women (age 2 , epirubicin 100 mg/m 2 , and cyclophosphamide 500 mg/m 2 every 21 days [FEC100], or fluorouracil 600 mg/m 2 , epirubicin 75 mg/m 2 , cyclophosphamide 900 mg/m 2 [tailored FEC] starting on day 1 and then every 21 days) or a taxane-based regimen (three cycles of docetaxel 100 mg/m 2 , intravenously infused over 1 h on day 1 every 21 days, followed by three cycles of intravenous epirubicin 90 mg/m 2 and docetaxel 75 mg/m 2 on day 1 every 21 days [T-ET]) at 42 centres in Europe. Randomisation was by use of a minimisation method that stratified patients by institution and initial tumour stage. The primary endpoint was progression-free survival (PFS) according to TP53 status. Analysis was by intention to treat. This is the final analysis of this trial. The study is registered with ClinicalTrials.gov, number NCT00017095. Findings 928 patients were enrolled in the FEC group and 928 in the T-ET group. TP53 status was not assessable for 183 (20%) patients in the FEC group and 204 (22%) patients in the T-ET group mainly because of low tumour-cell content in the biopsy. 361 primary endpoint events were recorded in the FEC group and 314 in the T-ET group. In patients with TP53 -mutated tumours, 5-year PFS was 59·5% (95% CI 53·4–65·1) in the T-ET group (n=326) and 55·3% (49·2–60·9) in the FEC group (n=318; hazard ratio 0·84, 98% CI 0·63–1·14; p=0·17). In patients with TP53 wild-type tumours, 5-year PFS was 66·8% (95% CI 61·4–71·6) in the T-ET group (n=398) and 64·7% (59·6–69·4) in the FEC group (n=427; 0·89, 98% CI 0·68–1·18; p=0·35). For all patients, irrespective of TP53 status, 5-year PFS was 65·1% (95% CI 61·6–68·3) in the T-ET group and 60·8% (57·3–64·2) in the FEC group (0·85, 98% CI 0·71–1·02; p=0·035). At the sites using FEC100 versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (75 [9%] of 803 vs 173 [21%] of 809, respectively), and neutropenia (653 [81%] vs 730 [90%], respectively). At the sites using tailored FEC versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (ten [8%] of 118 vs 26 [22%] of 116, respectively), and neutropenia (100 [85%] vs 115 [99%], respectively). Two patients died of toxicity during or within 30 days of chemotherapy completion and without disease relapse (one in each group). Interpretation Although TP53 status was prognostic for overall survival, it was not predictive of preferential sensitivity to taxanes. TP53 status tested by use of the yeast assay in this patient population cannot be used to select patients for an anthracycline-based chemotherapy versus a taxane-based chemotherapy. Funding US National Cancer Institute, La Ligue Nationale Contre le Cancer, European Union, Pharmacia, and Sanofi-Aventis.

Growth in Very Young Children Undergoing Chronic Peritoneal Dialysis

Abstract: Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic peritoneal dialysis at <24 months of age. From diagnosis to last observation, 57 patients were fed on demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from NG to demand feeding. North American and European centers accounted for nearly all feeding by gastrostomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation: 26% of North American children were obese and 50% of Turkish children were malnourished at last observation (P < 0.005). Body length decreased sharply during the first 6 to 12 months of life and then tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P < 0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible peritoneal dialysate and administration of growth hormone independently associated with improved length, even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible dialysis fluid, and growth hormone therapy associate with improved linear growth.

Rapid increase in the incidence of type 1 diabetes in Polish children from 1989 to 2004, and predictions for 2010 to 2025

Abstract: We analysed the temporal changes in the incidence of childhood type 1 diabetes and its demographic determinants in Poland from 1989 to 2004, validating the model with data from 1970 to 1989. We also estimated a predictive model of the trends in childhood diabetes incidence for the near future. Children under 15 years with newly diagnosed type 1 diabetes mellitus and drawn from seven regional registries in Poland were ascertained prospectively using the Epidemiology and Prevention of Diabetes study (EURODIAB) criteria. The type 1 diabetes incidence rates (IRs) were analysed in dependency of age, sex, seasonality, geographical region and population density. Time trends in IR were modelled using several approaches. The average incidence, standardised by age and sex, for 1989 to 2004 was 10.2 per 100,000 persons per year and increased from 5.4 to 17.7. No difference was found between boys and girls, or between urban and rural regions. In children above 4 years, IR was significantly higher in the population of northern Poland than in that of the country’s southern part, as well as in the autumn–winter season, this finding being independent of child sex. Based on the trend model obtained, almost 1,600 Polish children aged 0 to 14 years are expected to develop type 1 diabetes in 2010, rising to more than 4,800 in 2025. The estimates suggest at least a fourfold increase of IR between 2005 and 2025, with the highest dynamics of this increment in younger children. These estimates show that Poland will have to face a twofold higher increase in childhood type 1 diabetes than predicted for the whole European population. The dramatic increase could have real downstream effects on Poland’s healthcare system.

High glucose concentration affects the oxidant-antioxidant balance in cultured mouse podocytes.

Abstract: Hyperglycemia is well-recognized and has long-term complications in diabetes mellitus and diabetic nephropathy. In podocytes, the main component of the glomerular barrier, overproduction of reactive oxygen species (ROS) in the presence of high glucose induces dysfunction and increases excretion of albumin in urine. This suggests an impaired antioxidant defense system has a role in the pathogenesis of diabetic nephropathy. We studied expression of NAD(P)H oxidase subunits by Western blotting and immunofluorescence and the activities of the oxidant enzyme, NAD(P)H, and antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), in mouse podocytes cultured in a high glucose concentration (30 mM). We found long-term (3 and 5 days) exposure of mouse podocytes to high glucose concentrations caused oxidative stress, as evidenced by increased expression of Nox4 and activities of NAD(P)H oxidase (Δ 182%) and SOD (Δ 39%) and decreased activities of GPx (Δ -40%) and CAT (Δ -35%). These biochemical changes were accompanied by a rise in intracellular ROS production and accumulation of hydrogen peroxide in extracellular space. The role of Nox4 in ROS generation was confirmed with Nox4 siRNA. In conclusion, high glucose concentration affects the oxidant-antioxidant balance in mouse podocytes, resulting in enhanced generation of superoxide anions and its attenuated metabolism. These observations suggest free radicals may play an important role in the pathogenesis of diabetic nephropathy.

Blood pressure control and cardiovascular risk profile in hypertensive patients from central and eastern European countries: results of the BP-CARE study.

Abstract: Aims Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern European countries. Methods and results In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients’ age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure. Conclusion These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.

Cardiac Geometry in Children Receiving Chronic Peritoneal Dialysis: Findings from the International Pediatric Peritoneal Dialysis Network (IPPN) Registry

Abstract: Summary Background and objectives Left ventricular hypertrophy (LVH) is an independent risk factor and an intermediate end point of dialysis-associated cardiovascular comorbidity. We utilized a global pediatric registry to assess the prevalence, incidence, and predictors of LVH as well as its evolution in the longitudinal follow-up in dialyzed children. Design, setting, participants, & measurements Cross-sectional echocardiographic, clinical, and biochemical data were evaluated in 507 children on peritoneal dialysis (PD), and longitudinal data were evaluated in 128 patients. The 95th percentile of LV mass index relative to height age was used to define LVH. Results The overall LVH prevalence was 48.1%. In the prospective analysis, the incidence of LVH developing de novo in patients with normal baseline LV mass was 29%, and the incidence of regression from LVH to normal LV mass 40% per year on PD. Transformation to and regression from concentric LV geometry occurred in 36% and 28% of the patients, respectively. Hypertension, high body mass index, use of continuous ambulatory peritoneal dialysis, renal disease other than hypo/dysplasia, and hyperparathyroidism were identified as independent predictors of LVH. The use of renin-angiotensin system (RAS) antagonists and high total fluid output (sum of urine and ultrafiltration) were protective from concentric geometry. The risk of LVH at 1 year was increased by higher systolic BP standard deviation scores and reduced in children with renal hypo/dysplasia. Conclusions Using height-adjusted left ventricular mass index reference data, LVH is highly prevalent but less common than previously diagnosed in children on PD. Renal hypo/dysplasia is protective from LVH, likely because of lower BP and polyuria. Hypertension, fluid overload, and hyperparathyroidism are modifiable determinants of LVH. Clin J Am Soc Nephrol 6: ●●● –●●● , 2011. doi: 10.2215/CJN.05990710

Novel Functional Germline Variants in the VEGF Receptor 2 Gene and Their Effect on Gene Expression and Microvessel Density in Lung Cancer

Abstract: Purpose: VEGFR-2 plays a crucial role in mediating angiogenic endothelial cell responses via the VEGF pathway and angiogenesis inhibitors targeting VEGFR-2 are in clinical use. As angiogenesis is a host-driven process, functional heritable variation in KDR , the gene encoding VEGFR-2, may affect VEGFR-2 function, and ultimately, the extent of tumor angiogenesis. Experimental Design: We resequenced KDR using 24 DNAs each from healthy Caucasian, African American and Asian groups. Non-synonymous genetic variants were assessed for function using phosphorylation assays. Luciferase reporter gene assays were used to examine effects of variants on gene expression. KDR mRNA and protein expression, and microvessel density (MVD) were measured in non-small cell lung cancer (NSCLC) tumor samples and matching patient DNA samples were genotyped to test for associations with variants of interest. Results: KDR resequencing led to the discovery of 120 genetic variants, of which 25 had not been previously reported. Q472H had increased VEGFR-2 protein phosphorylation and associated with increased MVD in NSCLC tumor samples. -2854C and -2455A increased luciferase expression and associated with higher KDR mRNA levels in NSCLC samples. -271A reduced luciferase expression and associated with lower VEGFR-2 levels in NSCLC samples. -906C and 23408G, associated with higher KDR mRNA levels in NSCLC samples. Conclusions: This study has defined KDR genetic variation in three populations and identified common variants that impact on tumoral KDR expression and vascularization. These findings may have important implications for understanding the molecular basis of genetic associations between KDR variation and clinical phenotypes related to VEGFR-2 function.

Hypertension and sexual dysfunction: time to act.

Abstract: Abbreviations ACE: angiotensin-converting enzyme; ARBs: angiotensin receptor blockers; ESH: European Society of Hypertension; PDE: phosphodiesterase.Rationale for developing a working group on sexual dysfunctionSexual dysfunction is a common clinical problem that severely affects the quality of life

Specific detection of Salmonella enterica and Escherichia coli strains by using ELISA with bacteriophages as recognition agents

Abstract: The use of bacteriophages, instead of antibodies, in the ELISA-based detection of bacterial strains was tested. This procedure appeared to be efficient, and specific strains of Salmonella enterica and Escherichia coli could be detected. The sensitivity of the assay was about 105 bacterial cells/well (106/ml), which is comparable with or outperforms other ELISA tests detecting intact bacterial cells without an enrichment step. The specificity of the assay depends on the kind of bacteriophage used. We conclude that the use of bacteriophages in the detection and identification of bacteria by an ELISA-based method can be an alternative to the use of specific antibodies. The advantages of the use of bacteriophages are their environmental abundance (and, thus, a possibility to isolate various phages with different specificities) and the availability of methods for obtaining large amounts of phage lysates, which are simple, rapid, cheap, and easy.

Urinary tract infections in renal transplant recipients.

Abstract: Introduction Urinary tract infections (UTIs) are most common infections in renal transplant recipients and are considered a potential risk factor for poorer graft outcomes. Aim To evaluate incidence, clinical manifestations, microbiology, risk factors for UTIs, and the influence of UTIs on long-term renal graft function. Patients and methods We analyzed urine cultures with reference to clinical data of patients who received a renal transplantation from January to December 2009 with a 12-month follow-up. Results The 1170 urine cultures were correlated with clinical data from 89 renal transplant recipients, including 58.4% males and on overall mean age of 48 ± 14 years. The 151 episodes in 49 patients consisted of asymptomatic bacteriuria (65%, n = 98); lower UTIs (13%, n = 19); and upper UTIs (22%, n = 34), as well as five cases of bacteremia. Nearly 48% of UTIs were diagnosed during the first month posttransplantation. The most frequently isolated uropathogens were Enterococcus faecium (33%, n = 24) and Escherichia coli (31%, n = 23). Beginning from the second month, most frequently found bacterium in urine cultures was E coli (65% n = 51). Risk factors for posttransplant UTIs were female gender and a history of an acute rejection episode and/or a cytomegalovirus (CMV) infection. All patients with vesicoureteral reflux of strictures at the ureterovesical junction suffered recurrent UTIs ( n = 7). The evolution of renal graft function did not differ significantly between patients with versus without UTIs. Conclusions UTIs a frequent problem after kidney transplantation most commonly exist as asymptomatic bacteriuria. E coli and E faecium are ther predominant pathogens. Exposure to intensified immunosuppression due to acute rejection episodes or CMV infections represents a risk factor for UTIs. Vesicoureteral reflux or strictures at the ureterovesical junction are risk factors for recurrent UTIs. UTIs did not impair 1-year graft function.

Self-awareness of memory function in Parkinson's disease in relation to mood and symptom severity

Abstract: Objectives: In clinical practice, discrepancies are observed between self and proxy reports of various aspects of Parkinson's disease (PD). This study aimed at assessing self-awareness of memory function in PD both by comparing patients’ and caregivers’ questionnaire ratings of the patients’ memory and by correlating subjective ratings with verbal learning results. Method: Forty-five patient–proxy pairs participated in the study. Self-Rating Scale of Memory Functions was used as a questionnaire subjective measure. Auditory Verbal Learning Test (AVLT) was applied to assess verbal memory, Stroop test to assess cognitive control and Mini-Mental State Examination (MMSE) for global cognitive assessment. Results: Patient self-reports did not diverge appreciably from proxy reports when global scores were considered, but patient–proxy consistency was low for individual items with the exception of those referring to verbal recall. Both patient and proxy ratings were moderately correlated with the objective measure...

Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: assessment of effects on cognitive functions and general status of patients.

Abstract: BACKGROUND Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by deficiencies in enzymes involved in degradation of glycosaminoglycans. MPS type III (Sanfilippo disease) is clinically characterized mainly by progressive and severe behavioral disturbances and cognitive dysfunction. Recent 1-year experimental treatment of 10 patients with a genistein (4', 5, 7-trihydroxyisoflavone)-rich extract resulted in improvement of tested parameters, including cognitive and behavioral functions. MATERIAL/METHODS Eight pediatric patients with Sanfilippo disease were enrolled into the study. The modified version of the Brief Assessment Examination was used to assess cognitive functions. Moreover, 18 different parameters concerning changes in conditions of patients were assessed by their parents. RESULTS During the first year of the treatment, an improvement of cognitive functions in 7 patients and stabilization in 1 patient were assessed, while after the third year (2-year follow-up) further improvement was observed in 2 patients, stabilization in 3 patients and some deterioration in 3 patients. Monitoring of general and behavioral symptoms revealed improvement in all patients after the first year of the treatment, further improvement in 5 patients, and deterioration in 3 patients during the next 2 years. CONCLUSIONS We conclude that the treatment of Sanfilippo patients with a genistein-rich soy isoflavone extract (called gene expression-targeted isoflavone therapy [GET IT]) may be effective in either inhibition (in some patients) or slowing down (in other patients) of behavioral and cognitive problems over a longer period. An increased dose of genistein may improve the efficacy of the treatment.

Estimation of oxidative stress markers in chronic kidney disease.

Abstract: Changes mediated by oxidative stress are thought to be involved with atherosclerosis in patients with chronic kidney disease (CKD). The purpose of this study was to analyze the markers of oxidative damage and the activity of antioxidative enzymes as well as the total antioxidant capability in patients with different stages of CKD, both conventionally treated and dialyzed. We evaluated the oxidative modification of lipids (by oxidized low-density lipoprotein and malonodialdehyde levels) and proteins (by advanced oxidation protein products level). We also assessed the activity of paraoxonase-1 and glutathione peroxidases and total antioxidant status. Compared with the control group, the uremic patients, both dialyzed and nondialyzed, had higher levels of all studied plasma oxidative stress markers and decreased activity of antioxidative enzymes. Our results lead us to conclude that oxidative stress seems to be related rather to the uremic state than to the dialysis treatment. We also showed that estimating total antioxidant status in a simple test is unreliable for assessing the antioxidant ability of patients with CKD.

Neuroendocrinology of the skin: An overview and selective analysis.

Abstract: The concept on the skin neuro-endocrine has been formulated ten years ago, and recent advances in the field further strengthened this role. Thus, skin forms a bidirectional platform for a signal exchange with other peripheral organs, endocrine and immune systems or brain to enable rapid and selective responses to the environment in order to maintain local and systemic homeostasis. In this context, it is not surprising that the function of the skin is tightly regulated by systemic neuro-endocrine system. Skin cells and skin appendages not only respond to neuropeptides, steroids and other regulatory signals, but also actively synthesis variety of hormones. The stress responses within the skin are tightly regulated by locally synthesized factors and their receptor expression. There is growing evidence for alternative splicing playing an important role in stress signaling. Deregulation of the skin neuro-endocrine signaling can lead or/and be a marker of variety of skin diseases. The major problem in this area relates to their detailed mechanisms of crosstalk between skin and brain and between the local and global endocrine as well as immune systems.