bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Captopril Have a Direct Pro-Apoptotic Effect?
Authors: Buemi Michele , Allegra Alessandro , Marino Demetrio , Marino Maria Teresa , Medici Maria Antonietta , De Pasquale Giuseppe , Ruello Antonella , Corica Francesco , Frisina Nicola 
Published: April 2003

The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3.5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.
Effect of Hyperosmolality upon the Mesothelial Monolayer Exposed in vivo and in situ to a Mannitol-Enriched Dialysis Solution
Authors: Gotloib Lazaro , Wajsbrot Valery , Shostak Avshalom , Kushnier Raisa 
Published: April 2003

Studies done using the in vivo mouse model of population analysis of mesothelium showed that dialysis solutions containing high concentrations of glucose induced the development of a hypertrophic phenotype. Since these changes were neither related to the low pH nor to the presence of lactate buffer, we hypothesized that the presence of glucose was at the origin of the observed alterations. Theoretical analysis of the problem points to three possible mechanisms: hyperosmolality; metabolic changes derived from the high-glucose concentration itself, and/or the presence of products derived from the nonenzymatic degradation of glucose. The present study was designed to demonstrate or rule out the eventual effect of hyperosmolality upon the monolayer, applying the in vivo mouse model of population analysis of mesothelium. For this purpose, morphometric observations made in mice injected once a day during 30 consecutive days with a filter-sterilized 4.25% solution of mannitol (233.29 mM) were compared with those seen in intact mice and in a previously reported group of animals exposed to heat-sterilized fluid, having an equimolar concentration of glucose (235.9 mM), and the same osmolality (486 mosm/l) and electrolyte concentrations. The main findings observed in the mannitol-treated mice during the period of exposure included increased cell size and cytoplasmic surface area, as well as decreased cell viability. The regenerative capabilities of the exposed mesothelium remained intact. After a recovery period of 7 days, the aforementioned parameters reverted to normal values. This pattern is significantly different from the hypertrophic, senescent and low regenerative phenotype observed in mice treated with the high-glucose concentration solution. We conclude that, at least in the in vivo and in situ setup, the detrimental effects of hyperosmolality alone upon the exposed mesothelium are quite limited and fully reversible within a recovery period of 7 days.
Differential Distribution of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Proteins in Experimental Diabetic Rat Kidney
Authors: Miyatake Nobuyuki , Shikata Kenichi , Wada Jun , Sugimoto Hikaru , Takahashi Shin-Ichiro , Makino Hirofumi 
Published: April 2003

Insulin-like growth factor-1 (IGF-1) is a peptide growth factor, and its activity is modulated by interaction with the family of IGF binding proteins (IGFBP-1 to 6). IGF-1 is detected in rat kidney and has metabolic and growth effects. To explore the possible involvement of IGFBPs in glomerular hypertrophy in streptozotocin (STZ)-induced diabetic rat, the immunolocalization of IGF-1 and IGFBPs were investigated. IGF-1 was gradually increased in the glomeruli of diabetic rats and correlated with glomerular hypertrophy. IGFBP-1 was transiently increased at 1 week after the STZ injection and declined to control level during the following period. In contrast, IGFBP-4 was increased in the diabetic glomeruli throughout the observation period. With insulin treatment, the levels of IGF-1, IGFBP-1 and 4 were normalized and glomerular hypertrophy was prevented. Initial glomerular hypertrophy of diabetic nephropathy is a related IGF-1 action, which may be modulated by IGFBP-1 and 4.
High Glucose Induces a Hypertrophic, Senescent Mesothelial Cell Phenotype after Long in vivo Exposure
Authors: Gotloib Lazaro , Shostak Avshalom , Wajsbrot Valery , Kushnier Raisa 
Published: April 2003

Previous studies, done using our mouse model for population analysis of the mesothelium, showed evidence indicating that in vivo, long-term exposure (up to 30 days) of the peritoneum to high-glucose (4.25% <i>D</i>-glucose) concentration dialysis solutions resulted in a hypertrophic mesothelial phenotype characterized by increased cell surface area, multinucleation, low proliferative capabilities, reduced cell viability, and enhanced enzymatic activity. These elements that define a senescent population of cells were not related to the pH of the fluid and its osmolality, or to the presence of buffer lactate. The present study was designed to explore the adverse effects of a lactate-free, filter-sterilized, high-<i>D</i>-glucose concentration solution (4.25%) at normal pH and prepared in Hanks’ buffered salt solution after 2 h, 15 and 30 days of once a day intraperitoneal injection. Analysis of our observations indicate that in vivo exposure of the mesothelium to a high-glucose concentration induced a decreased density of the cell population, made up by larger and multinucleated cells, the viability of which was significantly lower than that observed in intact unexposed mice. The prevalence of mitosis showed an early and short-lived acceleration (up to 3 days), followed by values near zero during the rest of the follow-up period. So far, the main effect of the high-glucose concentration appears to result not from a mechanism of cytotoxicity, but from a substantial change in the life cycle of the exposed cell population, leading to their premature senescence and death in apoptosis. We hypothesize that this outcome may well be mediated by sustained oxidative stress derived from both a reduced production of scavengers, as well as the increased generation of oxygen-reactive species.
Hemodialysis Neutropenia Correlates with a Decreased Filterability and an Increase in the Number of Cytoplasmic Actin Filaments in Peripheral Blood Neutrophils, Which Is Preceded by a Decrease in the Number of Surface Expression of <i>L</i>-Selectin
Authors: Iijima Shigeruko , Otsuka Fujio , Hasegawa Yuichi , Koyama Akio 
Published: April 2003

In order to clarify the precise cellular mechanism of <i>hemodialysis neutropenia</i>, we examined the changes in the viscoelasticity of peripheral blood neutrophils using both the micropore and the microchannel filtration methods, and the changes in the neutrophil surface expression of Mac-1, <i>L</i>-selectin and sialyl Lewis X and the cytoplasmic expression of the actin filaments using a flow cytometric analysis during a dialysis session. Five patients with chronic renal failure were selected who showed a nadir leukocyte count in peripheral blood at 30 min after the initiation of the dialysis session. The neutrophil count also reached a nadir at 30 min and thereafter returned to almost the predialysis level by 180 min. Both the micropore filtration time and the microchannel passage time, which reflect the viscoelasticity of the peripheral blood neutrophils, correlated inversely with the neutrophil count. At the nadir of neutropenia, the neutrophils were observed to have become both adhesive and viscoelastic. The actin filaments in the neutrophil cytoplasm gradually increased in number from the start of dialysis, reaching a peak level at 30 min, and thereafter decreasing to predialysis levels. The Mac-1 expression continuously increased up from 30 min until the end of dialysis. The <i>L</i>-selectin expression first decreased at 15 min, but thereafter returned to predialysis levels within 60 min. The SLe<sup>x</sup> expression did not change throughout the course of the session. These results thus indicated the neutrophil counts during a dialysis session to inversely correlate with the viscoelasticity of the neutrophils expressed by the micropore filtration time or microchannel passage time, which possibly depends on the contents of cytoplasmic actin filaments. In addition, the shedding of <i>L</i>-selectin from neutrophil surface may also be involved in the first step of hemodialysis neutropenia.
The Possible Role of c-fos Protein in Hypothalamus in Sleep Disturbance in Chronic Uremic Rats
Authors: Kim Young Ok , Choi Euy Jin , Ahn Hee Jong , Park Cheol Whee , Yang Chul Woo , Jin Dong Chan , Kim Yong Soo , Chang Yoon Sik , Bang Byung Kee 
Published: April 2003

Sleep disturbance is very common in patients with chronic renal failure, but its mechanism is not clear. The activity of c-fos protein (FOS) in ventrolateral preoptic neurons (VLPO) is associated with the sleep pattern. The purpose of this study was to evaluate the relationship between sleep disturbance and the expression of FOS in VLPO of chronic uremic rats. Chronic uremia was induced by the 5/6 nephrectomized model. The movements of the rats were measured with infrared monitoring during the daytime (8.00–20.00) and nighttime (20.00–8.00). Rats were killed at 10.00 or 16.00 h for the daytime (uremic rats 7, control 8) and at 22.00 h for the nighttime (uremic rats 7, control 9). The expression of FOS in VLPO was examined with the immunohistochemical method. The number of recorded daytime movements in uremic rats was significantly higher than in control rats (458 ± 185 vs. 222 ± 41, p < 0.001), but the number of recorded nighttime movements in uremic rats was lower than in control rats (949 ± 430 vs. 1,618 ± 261, p < 0.001). In the daytime, the number of FOS immunoreactive cells in uremic rats was lower than in control rats (18.4 ± 5.3 vs. 42.8 ± 6.3, p < 0.001), but there was no difference between two groups in the nighttime (10.8 ± 8.4 vs. 12.5 ± 5.1, p = 0.62). There was a strong negative correlation between the number of recorded movements and the number of FOS immunoreactive cells in VLPO (r = –0.700, p < 0.001). This finding suggests that sleep disturbances in chronic uremic rats might be related to the decreased expression of FOS in VLPO.
Type IV Phosphodiesterase Inhibitor Is Effective in Prevention and Treatment of Experimental Crescentic Glomerulonephritis
Authors: Tam Frederick W.K. , Smith Jennifer , Agarwal Sangita , Karkar Ayman M. , Morel Delphine , Thompson Elizabeth M. , Pusey Charles D. 
Published: April 2003

<i>Background:</i> Tumour necrosis factor alpha (TNF-α) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-α synthesis. <i>Methods:</i> We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. <i>Results:</i> In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-α in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-α by 63% on day 7. TNF-α was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. <i>Conclusions:</i> Rolipram is effective both in prevention and treatment of experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-α.
Effects of Postdialysis Urea Rebound on the Quantification of Pediatric Hemodialysis
Authors: Marsenić Olivera , Pavličić Dubravka , Bigović Gordana , Peco-Antić Amira , Jovanović Olga 
Published: April 2003

Urea rebound (UR) causes single pool urea kinetic modeling (UKM), which is based on end-dialysis urea instead of its equilibrated value (Ceq), to erroneously quantify hemodialysis (HD) treatment. We estimated the impact of postdialysis UR on the results of formal variable volume single pool (VVSP) UKM [Kt/V, urea distribution volume (V), urea generation rate (G), normalized protein catabolic rate (nPCR), and urea reduction ratio (URR)] in children on chronic HD. Thirty-eight standard pediatric HD sessions in 15 stable patients (9 female, 6 male) aged 14.5 ± (SD) 3.28 years were investigated. The HD sessions lasted 3.75 ± 0.43 h. The single pool urea clearance was 4.84 ± 1.25 ml/min/kg. All HD sessions were evaluated by VVSP and URR (%) with postdialysis urea taken at the end of HD and with Ceq taken 60 min after the end of HD, incorporating double pool effects and representing true double pool values. The anthropometric V was calculated by Cheek and Mellits formulae for children. VVSP significantly overestimated Kt/V by 0.26 ± 0.18 U (1.68 ± 0.36 vs. 1.42 ± 0.30, p < 0.0001), i.e., 19.05 ± 13.07%, G/V (0.20 ± 0.04 vs. 0.18 ± 0.04, p < 0.0001), nPCR (1.26 ± 0.23 vs. 1.18 ± 0.22 g/kg/day, p < 0.0001), and URR (73.92 ± 6.49 vs. 69.22 ± 7.06, p < 0.0001). VVSP significantly underestimated kinetic V in comparison to anthropometric V (18.74 ± 4.04 vs. 20.76 ± 4.43 liters or expressed as V/body weight: 58 ± 8 vs. 65 ± 9%, p < 0.05), while double pool kinetic V was more accurate (21.45 ± 4.34 liters, V/body weight: 64 ± 6%, p > 0.05). We conclude that UR has a significant effect on all results of UKM even after standard pediatric HD, and the degree of this efffect is documented. We suggest an increase of the minimum required prescribed single pool Kt/V in children and reduction of any delivered single pool Kt/V by approxiamtely 0.26 Kt/V U. Overestimation of nPCR by approximately 0.08 g/kg/day and underestimation of V by 8.5% should be kept in mind.
Incidence of Acquired Renal Cysts in Biopsy Specimens
Authors: Liu Jian She , Ishikawa Isao , Horiguchi Takayasu 
Published: April 2003

<i>Aims:</i> This study investigated whether or not acquired renal cysts develop in patients with mild chronic renal failure. <i>Methods:</i> A retrospective study was carried out using renal biopsy specimens from 720 patients. A renal cyst was defined as a tubule dilated >200 µm. <i>Results:</i> Renal cysts were found in 21 of 720 renal biopsy specimens. Serum creatinine of 21 patients with renal cysts was significantly higher than that of 699 patients without cysts (2.59 ± 2.64 vs. 1.09 ± 0.79 mg/dl) (p < 0.0001). Poor renal function (serum creatinine >1.6 mg/dl) reveals more cyst formation on biopsy specimens than good renal function (serum creatinine <1.5 mg/dl). Cysts were observed in 11 of 607 (1.8%) patients less than 50 years of age and in 10 of 113 (8.8%) patients over 51 years. To exclude simple cysts which are commonly observed in older subjects, 11 patients under 50 years of age were extensively examined. Mean serum creatinine was 2.98 ± 3.06 mg/dl (0.7–10.4 mg/dl). These 11 patients revealed low creatinine clearance of 47.5 ± 25.6 ml/min (5–71 ml/min). Creatinine clearances in 7 patients were 52–71 ml/min (serum creatinine 0.7–2.0 mg/ dl). One of 11 biopsy specimens with cysts was examined by immunohistochemistry on lectin. This specimen was positive for tetragonolobus lectin and negative for peanut lectin, suggesting that the epithelial cells lining the cyst were derived from proximal tubules, unlike those of simple cysts. <i>Conclusion:</i> These results suggest that low normal renal function such as creatinine clearances 52–71 ml/min due to nephron loss is sufficient to induce acquired cyst development in various renal diseases.
Protective Effect of Pyruvate upon Cultured Mesothelial Cells Exposed to 2 m<i>M</i> Hydrogen Peroxide
Authors: Shostak Avshalom , Gotloib Lazaro , Kushnier Raisa , Wajsbrot Valery 
Published: April 2003

Rat peritoneal mesothelial cells in culture have the capability of generating hydrogen peroxide. Exposure of these cells to glucose-enriched, lactated-buffered fluids for peritoneal dialysis significantly increases the production of H<sub>2</sub>O<sub>2</sub>. Increased liberation of oxygen radicals also involves the risk of damaging the peritoneal membrane. Pyruvate being a natural oxidant scavenger abundantly present in mammalian cells, we hypothesized that its protective effects facing H<sub>2</sub>O<sub>2</sub> can eventually be of relevance for the mesothelial monolayer of patients on long-term peritoneal dialysis. So far, we designed an experimental study in which rat peritoneal mesothelial cells in culture were exposed to 2 m<i>M</i> H<sub>2</sub>O<sub>2</sub>. Cell damage was estimated in terms of decreased capability of the mitochondrial dehydrogenases to reduce MTT. Addition of 2 m<i>M</i> sodium pyruvate to the medium prevented the negative effect of hydrogen peroxide. The MTT/protein values for the control group were 0.00357 ± 0.00075. The ratio after exposure to 2 m<i>M</i> H<sub>2</sub>O<sub>2</sub> was 0.00217 ± 0.00028, whereas that detected in cells incubated in H<sub>2</sub>O<sub>2</sub> plus pyruvate was 0.00325 ± 0.0082 (p < 0.05). These results indicate that pyruvate protected rat peritoneal mesothelial cells in culture against oxidant injury. These data are one more piece of evidence pointing at pyruvate as a potentially useful buffer for peritoneal dialysis solutions.
Assessing Residual Renal Function and Efficiency of Hemodialysis – an Application for Urographic Contrast Media
Authors: Sterner G. , Frennby B. , Månsson S. , Ohlsson A. , Prütz K.G. , Almén T. 
Published: April 2003

<i>Background:</i> In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1,550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300–5,000 u. <i>Methods:</i> Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. <i>Results:</i> In the 10 anuric patients the extrarenal clearances (mean ± SD) were 2.5 ± 1.1 and 2.7 ± 1.1 ml/min/1.73 m<sup>2</sup> for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r<sup>2</sup> = 0.853 for iohexol, r<sup>2</sup> = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 ± 16 and 58 ± 11 ml/min/1.73 m<sup>2</sup> when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8–10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. <i>Conclusions:</i> A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.
Increased Rate of Adenine Incorporation into Adenine Nucleotide Pool in Erythrocytes of Patients with Chronic Renal Failure
Authors: Marlewski Maciej , Smolenski Ryszard T. , Szolkiewicz Marek , Aleksandrowicz Zenon , Rutkowski Boleslaw , Swierczynski Julian 
Published: April 2003

<i>Background:</i> Elevated purine nucleotide pool (mainly ATP) in erythrocytes of patients with chronic renal failure (CRF) is a known phenomenon, however the mechanism responsible for this abnormality is far from being clear. We hypothesize that the increased rate of adenine incorporation into adenine nucleotide pool is responsible for the elevated level of ATP in uremic erythrocytes. <i>Methods:</i> In chronically uremic patients we evaluated using HPLC technique: (a) plasma adenine concentration; (b) the rate of adenine incorporation into adenine nucleotide pool in uremic erythrocytes. Additionally, the effect of higher than physiological phosphate concentration (2.4 m<i>M</i>) and lower than physiological pH (7.1) on adenine incorporation into erythrocytes adenine nucleotide pool was investigated. Healthy volunteers with normal renal function served as control. <i>Results:</i> The concentration of adenine in plasma of CRF patients was found to be significantly higher than in plasma of healthy subjects. In contrast, adenosine concentration was similar both in healthy humans and in CRF patients. In isolated erythrocytes of uremic patients (incubated in the medium pH 7.4, containing 1.2 m<i>M</i> inorganic phosphate) adenine was incorporated into adenine nucleotide pool at a rate approximately 2-fold higher than in erythrocytes from healthy subjects. The rate of adenosine incorporation into adenine nucleotide pool was similar in erythrocytes of both studied groups. Incubation of erythrocytes obtained from healthy subjects in the medium pH 7.4, containing 2.4 m<i>M</i> inorganic phosphate, caused the increase of adenine incorporation into adenine nucleotide pool by about 60%. Incubation of the cells in the pH 7.1 buffer containing 2.4 m<i>M</i> inorganic phosphate increased the rate of adenine incorporation into adenylate approximately 2-fold as compared to erythrocytes incubated in the medium pH 7.4 containing 1.2 m<i>M</i> inorganic phosphate. Erythrocytes obtained from uremic patients and incubated in the pH 7.1 medium containing 2.4 m<i>M</i> phosphate incorporated adenine into adenine nucleotide pool at a rate similar to erythrocytes incubated in the medium pH 7.4 containing 1.2 m<i>M</i> phosphate. Erythrocytes obtained from either healthy subjects or from patients with CRF and incubated in the presence of higher than physiological concentration of inorganic phosphate (2.4 m<i>M</i>) and lower than physiological pH (7.1) did not exhibit any increase in the rate of adenisine incorporation into adenine nucleotide pool. <i>Conclusion:</i> These results suggest that the increased rate of adenine incorporation into adenine nucleotide pool could be partially responsible for the increased concentration of ATP in uremic erythrocytes.