The Interplay between Gut Microbiota and Cognitive Functioning in the Healthy Aging Population: A Systematic Review.

BACKGROUND: The gut microbiota in healthy older individuals typically show a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, alongside an increase in pro-inflammatory microbes such as Enterobacteriaceae and Clostridia. These changes contrast with younger and middle-aged individuals and appear to correlate with cognitive status. Although there is extensive research on gut microbiota and cognitive functions in cognitively impaired elderly individuals, its impact on cognitively healthy elderly populations has not been extensively studied. METHOD: A comprehensive literature search was conducted across PubMed, EBSCO, Web of Science, and Scopus databases to identify studies exploring the relationship between gut microbiota composition and cognitive functioning in healthy older adults. During the literature screening process, each record was initially assessed by its title, abstract, and keywords to exclude articles that did not align with the scope of this review. Three authors independently screened and retrieved the records. The inclusion criteria included: (1) publication in peer-reviewed journals; (2) studies involving neurologically, cognitively, and medically healthy populations; (3) participants identified as older adults, defined for this review as individuals aged 45 years and older due to the limited number of records; (4) analysis of gut microbiota; and (5) assessment of cognitive function. Subsequently, full texts were analyzed to determine eligibility. The exclusion criteria encompassed: (1) incorrect publication type; (2) inappropriate sample population; (3) unsuitable study design; (4) absence of one or more inclusion criteria; and (5) studies based on animal research. A risk of bias assessment was performed for each included study using the Joanna Briggs Institute (JBI) checklist, ensuring all selected studies met established quality standards. RESULTS: A total of 6 eligible research articles from a possible 1752 published until March 2024 were identified and included. We categorized the included studies into two groups based on their focus: the taxonomic composition of gut microbiota and the alpha diversity, which is the variety of organisms within a sample. Additionally, two methods were identified for assessing cognition: neuropsychological tests and physiological measurements, notably electroencephalography (EEG). The studies show varying results regarding the abundance of specific bacterial taxa and their cognitive associations. Notably, the relationship between certain bacteria and cognition may vary when analyzed at different taxonomic levels, such as phylum versus family. CONCLUSIONS: Changes in gut microbiota composition in the elderly, even without a cognitive impairment diagnosis, could potentially serve as early biological markers for Alzheimer's disease or other dementias before mild cognitive impairment appears.

Proteomic Profiling of Leukocytes Reveals Dysregulation of Adhesion and Integrin Proteins in Chronic Kidney Disease-Related Atherosclerosis.

A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes' diapedesis process that is very pronounced in CKD's advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.

Mass Spectrometry-Based Lipidomics Reveals Differential Changes in the Accumulated Lipid Classes in Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by the progressive loss of functional nephrons. Although cardiovascular disease (CVD) complications and atherosclerosis are the leading causes of morbidity and mortality in CKD, the mechanism by which the progression of CVD accelerates remains unclear. To reveal the molecular mechanisms associated with atherosclerosis linked to CKD, we applied a shotgun lipidomics approach fortified with standard laboratory analytical methods and gas chromatography-mass spectrometry technique on selected lipid components and precursors to analyze the plasma lipidome in CKD and classical CVD patients. The MS-based lipidome profiling revealed the upregulation of triacylglycerols in CKD and downregulation of cholesterol/cholesteryl esters, sphingomyelins, phosphatidylcholines, phosphatidylethanolamines and ceramides as compared to CVD group and controls. We have further observed a decreased abundance of seven fatty acids in CKD with strong inter-correlation. In contrast, the level of glycerol was elevated in CKD in comparison to all analyzed groups. Our results revealed the putative existence of a functional causative link-the low cholesterol level correlated with lower estimated glomerular filtration rate and kidney dysfunction that supports the postulated "reverse epidemiology" theory and suggest that the lipidomic background of atherosclerosis-related to CKD is unique and might be associated with other cellular factors, i.e., inflammation.

Selected Atherosclerosis-Related Diseases May Differentially Affect the Relationship between Plasma Advanced Glycation End Products, Receptor sRAGE, and Uric Acid.

Our study aimed to identify the relationship between advanced glycation end products (AGEs), soluble receptor for advanced glycation end products (sRAGE), the AGEs/sRAGE, and uric acid (UA) levels in selected atherosclerosis diseases, i.e., abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD), resulting from apparent differences in oxidative stress intensity. Furthermore, we suggest that increased AGEs levels may stimulate an antioxidant defense system reflected by the UA level. The studied group size consisted of 70 AAA patients, 20 AIOD patients, 50 patients in the pre-dialyzed group (PRE), and 35 patients in the hemodialyzed group (HD). The enzyme-linked immunosorbent assay was used to measure AGEs and sRAGE levels. We found a significantly higher concentration of AGEs in CKD patients as compared to AAA and AIOD patients. Furthermore, the sRAGE level was higher in the CKD patients in comparison to AIOD and AAA patients. UA level was significantly higher in the PRE group compared to AAA patients. In conclusion, the diseases included in this study differ in the anti- and prooxidant defense system, which is reflected in the relations between the AGEs, the sRAGE, the AGEs/sRAGE ratio, as well as the UA levels.

The association of serum soluble Klotho levels and residual diuresis and overhydration in peritoneal dialysis patients.

BACKGROUND: Klotho, originally identified as an anti-aging factor, is a transmembrane protein expressed in the kidney. It has been reported that Klotho deficiency could be associated with a loss of residual renal function and cardiovascular complications in peritoneal dialysis (PD) patients. OBJECTIVES: The main aim of the study was to evaluate whether serum levels of Klotho correlate with residual diuresis and hydration status in PD patients. MATERIAL AND METHODS: The cross-sectional study involved 57 PD patients ≥18 years of age who had been on PD ≥ 3 months. Serum Klotho was measured using high-sensitivity enzyme-linked immunosorbent assay (ELISA). Hydration status was assessed with bioimpedance analysis (BIA). RESULTS: Serum levels of soluble Klotho ranged from 100 pg/mL to 700 pg/mL. The patients were divided into 2 subgroups, with Klotho levels below and above the median (260 pg/mL). The data revealed a tendency for lower residual diuresis (1.3 ±1.0 L vs 1.8 ±0.8 L; p = 0.055) in patients with lower levels of Klotho in serum. Serum Klotho correlated negatively with overhydration according to BIA (r = -0.27; p = 0.044) and positively with residual diuresis (r = 0.26; p = 0.045). CONCLUSIONS: Soluble Klotho correlates inversely with hydration status in BIA. Residual urine output, but not dialysis parameters, could be associated with the levels of serum soluble Klotho in PD patients.

Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases.

OBJECTIVES: The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). DESIGN AND METHODS: The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). RESULTS: The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. CONCLUSIONS: AAA, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.

The importance of residual renal function in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) patients with preserved residual diuresis have a lower risk of death and complications. Here we analyzed associations between residual diuresis and presence of fluid overload and biomarkers of cardiac strain and nutrition in PD patients. METHODS: Among 44 PD patients placed into three subgroups, depending on volume of residual diuresis (group A ≤ 500; group B 600-1900; and group C ≥ 2000 mL/day), we examined: overhydration (OH) assessed by bioimpedance analysis (BIA; yielding OH index OHBIA) and by clinical criteria (edema and hypertension); nutritional status (by subjective global assessment, SGA); metabolic status (electrolytes, serum lipid profile, CRP, and albumin); biomarkers of fluid overload and cardiac strain (N-terminal probrain natriuretic peptide, NT-proBNP, and troponin T, TnT); and, echocardiography and chest X-ray. RESULTS: With increasing residual diuresis in group A, B and C, fewer patients had signs of overhydration defined as OHBIA > 1.1 L (75.0, 42.9 and 33.3 %) or peripheral edema (25.0, 21.4 and 0 %) and NT-proBNP (15199 ± 16150 vs. 5930 ± 9256 vs. 2600 ± 3907 pg/mL; p < 0.05) and TnT (0.15 ± 0.17 vs. 0.07 ± 0.09 vs. 0.04 ± 0.03 ng/mL; p < 0.05) were significantly lower. Significant differences were found also in ejection fraction, SGA, and total cholesterol, albumin and hemoglobin levels whereas blood pressures and serum CRP did not differ significantly. CONCLUSION: Signs of OH and cardiac strain are common in PD patients, even in those with diuresis of 1000-2000 mL/day and with no clinical signs or symptoms, suggesting that even moderate decrease in residual renal function in PD patients associate with OH and other complications.

iTRAQ-based proteomic analysis of plasma reveals abnormalities in lipid metabolism proteins in chronic kidney disease-related atherosclerosis.

Patients with chronic kidney disease (CKD) have a considerably higher risk of death due to cardiovascular causes. Using an iTRAQ MS/MS approach, we investigated the alterations in plasma protein accumulation in patients with CKD and classical cardiovascular disease (CVD) without CKD. The proteomic analysis led to the identification of 130 differentially expressed proteins among CVD and CKD patients and healthy volunteers. Bioinformatics analysis revealed that 29 differentially expressed proteins were involved in lipid metabolism and atherosclerosis, 20 of which were apolipoproteins and constituents of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Although dyslipidemia is common in CKD patients, we found that significant changes in apolipoproteins were not strictly associated with changes in plasma lipid levels. A lack of correlation between apoB and LDL concentration and an inverse relationship of some proteins with the HDL level were revealed. An increased level of apolipoprotein AIV, adiponectin, or apolipoprotein C, despite their anti-atherogenic properties, was not associated with a decrease in cardiovascular event risk in CKD patients. The presence of the distinctive pattern of apolipoproteins demonstrated in this study may suggest that lipid abnormalities in CKD are characterized by more qualitative abnormalities and may be related to HDL function rather than HDL deficiency.

Label-Free Quantitative Proteomics Reveals Differences in Molecular Mechanism of Atherosclerosis Related and Non-Related to Chronic Kidney Disease.

The major cause of mortality in patients with chronic kidney disease (CKD) is atherosclerosis related to traditional and non-traditional risk factors. However, the understanding of the molecular specificity that distinguishes the risk factors for classical cardiovascular disease (CVD) and CKD-related atherosclerosis (CKD-A) is far from complete. In this study we investigated the disease-related differences in the proteomes of patients with atherosclerosis related and non-related to CKD. Plasma collected from patients in various stages of CKD, CVD patients without symptoms of kidney dysfunction, and healthy volunteers (HVs), were analyzed by a coupled label-free and mass spectrometry approach. Dysregulated proteins were confirmed by an enzyme-linked immunosorbent assay (ELISA). All proteomic data were correlated with kidney disease development and were subjected to bioinformatics analysis. One hundred sixty-two differentially expressed proteins were identified. By directly comparing the plasma proteomes from HVs, CKD, and CVD patients in one study, we demonstrated that proteins involved in inflammation, blood coagulation, oxidative stress, vascular damage, and calcification process exhibited greater alterations in patients with atherosclerosis related with CKD. These data indicate that the above nontraditional risk factors are strongly specific for CKD-A and appear to be less essential for the development of "classical" CVD.

Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease--systems and clinical approach.

The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory.

Deeper insight into chronic kidney disease-related atherosclerosis: comparative proteomic studies of blood plasma using 2DE and mass spectrometry.

BACKGROUND: Atherosclerosis is a major cause of cardiac events and mortality in patients suffering from chronic kidney disease (CKD). Moreover, the risk of cardiovascular disease (CVD) development in patients with CKD increases as kidney function declines. Although the close connection between atherosclerosis and kidney dysfunction is undeniable, particular risk factors and specific mechanisms that promote CVD in patients with CKD remain unclear. To gain insight into better recognition of the mechanisms of accelerated atherosclerosis in patients with CKD, we performed a comparative proteomic analysis of blood plasma from patients in various stages of CKD and thus distinct progression of atherosclerosis (n = 90), patients with advanced CVD and normal renal function (n = 30) and healthy volunteers (n = 30). METHODS: Plasma samples were depleted using affinity chromatography and divided into three fractions: high-abundant, low-abundant and low-molecular weight proteins. The first two fractions were analyzed by two-dimensional gel electrophoresis and mass spectrometry, the last one has been subjected to direct MS/MS analysis. A proteomic profiles for high-abundant, low-abundant and low-molecular weight proteins fractions were obtained. Differential accumulated proteins were confirmed by selected reaction monitoring analysis (SRM). The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. RESULTS: Forty-nine proteins (13 high- and 36 low-molecular mass) showed differences in accumulation levels. For eleven of them differential expression were confirmed by selected reaction monitoring analysis. Bioinformatic analysis showed that identified differential proteins were related to three different processes: the blood coagulation cascade, the transport, binding and metabolism of lipoproteins and inflammatory processes. CONCLUSIONS: Obtained data provide an additional line of evidence that different molecular mechanisms are involved in the development of CKD- and CVD-related atherosclerosis. The abundance of some anti-atherogenic factors revealed in patients with CKD suggests that these factors are not associated with the reduction of atherosclerosis progression in CKD that is typically observed in "classical" CVD. Moreover, obtained data also suggest that mechanism of CVD acceleration may be different in initial and advanced stages of CKD. Undoubtedly, in advanced stages of CKD inflammation is highly pronounced.

The polymorphism of the ACE gene affects left ventricular hypertrophy and causes disturbances in left ventricular systolic/diastolic function in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequently occurring autosomal diseases inherited in the dominant manner. Due to this, lesions in the cardiovascular system of ADPKD patients have caught the attention of clinical investigators worldwide. The aim of the study was to analyse cardiovascular complications in ADPKD patients with a focus on left ventricular hypertrophy (LVH) and selected components of its systolic/diastolic function based on echocardiography. The study was conducted on 55 patients with ADPKD (24 males, 31 females), subdivided into three groups according to the stage of chronic kidney disease (CKD). The patient group with ADPKD and ESRD (group C) manifested an increased incidence of the D allele as compared to group A and group B (χ(2) = 4.217, P = 0.04). In all ADPKD patients with the DD genotype, left ventricular mass (LVM), posterior wall thickness (PWT), and interventricular septal thickness (IVS) were significantly higher compared to patients possessing the II and ID genotypes (P < 0.02, P < 0.003, and P < 0.009, resp.). The DD genotype exists more frequently in ADPKD patients with ESRD and is associated with a higher occurrence of LVH and disturbances in systolic-diastolic function when compared to ADPKD ESRD patients with the II and ID genotypes.

Differences in the psychological and hormonal presentation of lean and obese patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders found in women of reproductive age. Differences in hormonal and metabolic profiles are observed in groups of patients with normal and elevated BMI. Cause of disturbances observed in the two groups of patients with PCOS is analyzed. The aim of the study is to assess whether psychological parameters of lean and obese patients with PCOS are comparably significantly different and whether there is a correlation between these characteristics and the concentration of various hormones. PARTICIPANTS AND PROCEDURES: The study consisted of 20 patients with diagnosed polycystic ovary syndrome and 20 healthy women of similar age. Both groups were stratified according to BMI. Specific psychological parameters and hormones were estimated in all patients. RESULTS: In our study, we found that patients with BMI <25 represented personality traits associated with lower resistance to stress. We also observed significantly higher ACTH levels in the same group as compared to patients with BMI >25. A correlation between plasma ghrelin and the severity of anxiety experienced by test subjects was also observed. CONCLUSION: The type of personality and emotional disorders in lean PCOS patients may lead to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and disturbences in hypothalamic-pituitary-ovary (HPO) axis. The results suggest participation of primary hypothalamic dysfunction in the pathogenesis of PCOS in patients with specific fenotype. Ghrelin is a hormone that may affect the symptoms of PCOS in lean patients. Psychological therapy should be considered as a permanent element in the therapeutic plan provided to PCOS patients.

Pregnancy in diabetic woman with coexisting hypothyroidism, coronary artery disease and with early onset nephrotic syndrome--a case report.

We present a case of pregnancy in 28-years old nulliparous woman with an over 20-years long history of diabetes, hypothyroidism, diabetic nephropathy with nephrotic syndrome, retinopathy and coronary artery disease treated with PCA prior the pregnancy (class H diabetes, according to White classification).

Vitamin K status in peritoneally dialyzed patients with chronic kidney disease.

Abnormal vitamin K status was documented in patients with chronic kidney diseases (CKD), especially those undergoing hemodialysis. The data related to patients undergoing peritoneal dialysis (PD) are contradictory. Therefore, in the present study we aimed to evaluate vitamin K status in patients with CKD who are treated with continuous ambulatory PD. Twenty-eight patients entered into the study. Dialysis vintage ranged from 3 to 89 months. Vitamin K status was assessed in all subjects using undercarboxylated prothrombin measurement (PIVKA-II). In addition, total protein and albumin levels, total cholesterol, LDL cholesterol, triglyceride, calcium, urea and creatinine concentrations were determined. PIVKA-II concentrations were abnormal in 13 (46.4 %) subjects. BMI values, both total and LDL cholesterol concentrations were significantly higher in patients with than those without vitamin K deficiency. Moreover, PIVKA II levels correlated with BMI values (r = 0.441, p < 0.019), LDL cholesterol (r = 0.434, p < 0.021) and creatinine (r = 0.406, p< 0.032) concentrations. However, through the use of logistic regression analysis and multiple regression analysis, no clinical factor was documented to be the independent risk factor of vitamin K deficiency. In conclusion, vitamin K deficiency is a frequent condition in peritoneally dialyzed patients. Assessment of vitamin K status should become a standard procedure in this group of patients.

Chronic kidney disease-related atherosclerosis - proteomic studies of blood plasma.

BACKGROUND: Atherosclerosis is considered the major cause of the dramatic increase in cardiovascular mortality among patients suffering from chronic kidney disease (CKD). Although the close connection between atherosclerosis and kidney dysfunction is undeniable, factors enhancing CKD-mediated plaque formation are still not well recognized. RESULTS: To increase our knowledge of this process we carried out a comparative proteomic analysis of blood plasma proteins isolated from 75 patients in various stages of renal dysfunction (CKD group), 25 patients with advanced cardiovascular disease (CVD group) and 25 healthy volunteers (HV group). The collected samples were subjected to 2D electrophoresis. Then, individual proteins were identified by mass spectrometry. The comparative analysis involving CKD and HV groups showed a differential accumulation of α-1-microglobulin, apolipoprotein A-IV, γ-fibrinogen and haptoglobin in patients with kidney disease. Exactly the same proteins were identified as differentially expressed when proteomes of CVD patients and HV were compared. However, a direct comparison of CKD and CVD groups revealed significant differences in the accumulation of two proteins: α-1-microglobulin and apolipoprotein A-IV. CONCLUSIONS: The obtained results indicate that at least two processes differentially contribute to the plaque formation in CKD- and CVD-mediated atherosclerosis. It seems that the inflammatory process is more intense in CKD patients. On the other hand, the down- and up-regulation of apolipoprotein A-IV in CVD and CKD groups, respectively, suggests that substantial differences exist in the efficacy of cholesterol transport in both groups of patients.

[Results of anemia treatment with darbepoetin alfa and erythropoietin beta in patients with chronic kidney disease]. / Wyniki leczenia niedokrwistosci darbepoetyna alfa i erytropoetyna beta u chorych na przewlekla chorobe nerek w okresie przeddializacyjnym.

UNLABELLED: The aim of study was to analyze the results of anemia treatment with darbepoetin alfa and erythropoietin beta in patients with chronic kidney disease (3-5 stage of CKD) in predialysis period. MATERIAL AND METHODS: In the study the results of anemia treatment with darbepoetin alfa and erythropoietin beta were analyzed in respectively 35 and 20 patients during 11 months, and its influence on blood pressure and the rate of progression of chronic kidney disease. After 2 months of darbepoetin alfa treatment 10 mg/month and after 4 months of darbepoetin alfa treatment 20 mg/month the hemoglobin target serum levels in male and female patients were reached. In 3 patients the hemoglobin serum level was increased over 13 g/dl and was stable up to the end of treatment. During 11 months observation the value of blood pressure was not changed. Similarly, a creatinine serum level was stable in females but increased in males. Therapy with darbepoetin alfa was well tolerated, however some patients were complained for subcutaneous injection pain. RESULTS: After erythropoietin beta treatment 2000 IU/week the hemoglobin target level in serum was achieved in 3 females after 9 months and 7 males after 6 months. In 3 patients, in one male after 6 months and two females after 8 months the hemoglobin serum levels were increased over 13 g/dl and was stable up to the end of treatment. CONCLUSIONS: During 11 months of observation blood pressure was not changed but a creatinine serum level was increased in females and in males. Erythropoietin beta was well tolerated and injection pain was smaller compared to darbepoetin alfa.

Human peritoneal fibroblasts are a potent source of neutrophil-targeting cytokines: a key role of IL-1beta stimulation.

Polymorphonuclear leukocyte (PMN) infiltration is a cardinal feature of peritonitis. CXC chemokine ligands 1 and 8 (CXCL1 and CXCL8), and the cytokine granulocyte colony-stimulating factor (G-CSF) are the key mediators of PMN accumulation. Increasing evidence points to an important role of human peritoneal fibroblasts (HPFB) in the response of the peritoneum to infection. We have examined the synthesis of PMN-targeting cytokines by HPFB exposed to intraperitoneal milieu as represented by peritoneal dialysate effluent (PDE) from patients undergoing peritoneal dialysis. PDE obtained during peritonitis, but not during infection-free periods, significantly increased production of CXCL1, CXCL8, and G-CSF by HPFB. The effect was largely blocked by antibodies to interleukin-1beta (IL-1beta), whereas neutralization of tumor necrosis factor-alpha (TNFalpha) had no major effect. Similar pattern of inhibition was observed when HPFB were exposed to conditioned media from endotoxin-stimulated peritoneal macrophages. Significance of IL-1beta stimulation was further shown in experiments with recombinant cytokines. Compared with TNFalpha, exposure of HPFB to recombinant IL-1beta resulted in a much higher release of PMN-targeting cytokines. The assessment of mRNA degradation revealed that the IL-1beta-induced transcripts of CXCL1, CXCL8, and G-CSF were more stable compared with those induced by TNFalpha. These data indicate that HPFB can be a significant source of PMN-targeting cytokines when stimulated with IL-1beta in the inflamed peritoneum.

[Hypotonia in renal failure patients undergoing dialysis therapy]. / Hipotonia u chorych na przewlekla niewydolnosc nerek poddanych dializoterapii.

In this paper we present the current reviews on the causes, symptoms, prevalence and clinical importance of hypotonia in chronic renal failure patients undergoing dialysis therapy. The results of clinical studies indicate that persistent hypotonia in dialysis patients is associated with increased mortality.