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Lazaro Gotloib

Publications and source records attributed to Lazaro Gotloib.

11 recordsLinked to original sources
PubMed2006

Repopulation of the mesothelial monolayer during long-term experimental peritoneal dialysis.

BACKGROUND: Repopulation of the mesothelial monolayer after focal exfoliation, having the monolayer in vivo and in situ exposed to dialysis solutions, has not been thoroughly investigated. This study describes repopulation of a 'doughnut' like mesothelial ring exfoliated from the anterior liver surface of rats. METHODS: Animals were divided into 5 groups of 20 rats each. Group 1 - control unexposed animals: mesothelial cell imprints were taken after 1 (5 rats), 5 (5 rats), and 15 (10 rats) days following the procedure of exfoliation. Group 2 - sham injected animals. Group 3 - rats IP injected once a day, during 30 consecutive days with Hank's balanced salt solution. Groups 4 and 5 - same experimental protocol, but injecting 4.25% glucose single bag or 7.5% Icodextrin PDF. Imprints and/or biopsies were taken after a recovery period of 15 days, counted from the last IP injection. RESULTS: Density distribution of mesothelial cells in group 2 was not significantly different from that seen in unexposed rats, whereas that seen in group 3 Hank's balanced salt solution was marginally but significantly lower (p < 0.05) from that seen in controls. Eighty five percent of rats injected with 4.25% glucose developed fibrous adhesions, binding up together the exfoliated liver surface and the diaphragmatic muscle. For Icodextrin treated rats, the prevalence of fibrous adhesions was 95%. CONCLUSIONS: The 'doughnut' experimental model appears as a promising tool for in vivo and in situ investigation of mesothelial repopulation. Both osmotic agents substantially restrain mesothelial repopulation, leading to repair by connective tissue.

Animals↗
PubMed2006

The impact of peritoneal dialysis upon quality of life and mortality of patients with end-stage congestive heart failure.

BACKGROUND: Aged patients affected by congestive heart failure refractory to pharmacologic therapy, coupled with severe comorbidities that preclude heart transplantation have a gloomy prognosis. Use of automated peritoneal dialysis resulted in a significantly improved quality of life and survival. METHODS: Twenty patients (mean age: 65.7 +/- 7.7 years) with severe congestive heart failure (Class IV-NYHA) and a high Charlson comorbidity index (7.8 +/- 1.8) were treated by means of automated peritoneal dialysis (3 sessions/week, 8 h each). The period of follow-up ranged between 7 and 35 months (19.8 +/- 7.4 months). RESULTS: After 1 year of follow-up, all patients showed functional (Class I-NYHA) and hemodynamic improvement: left cardiac work index increased from 2.33 +/- 0.69 to 2.59 +/- 0.47 kg/min/m(2) (p < 0.01); systolic times ratio was significantly reduced (from 61.14 +/- 12.57 to 39.18 +/- 13.44%, p < 0.01); and the thoracic fluid contents was substantially reduced (from 0.04 +/- 0.005 to 0.003 +/- 0.0001 Omega). A marked drop of hospitalization days was observed. CONCLUSIONS: Automated peritoneal dialysis appears as a promising tool for treating patients suffering from refractory, end stage congestive heart failure. Improvement of cardiac function may result from clearing the blood from middle molecular weight myocardial depressant substances, including atrial natriuretic peptide. Results of this investigation are a call for a prospective multicenter study in order to confirm these promising observations.

Aged↗
PubMed2005

Peritoneal dialysis in refractory end-stage congestive heart failure: a challenge facing a no-win situation.

BACKGROUND: Current medical therapeutic strategies for refractory congestive heart failure (CHF) in the population of 65 years and older with contraindications for heart transplantation are limited. Peritoneal dialysis applied to CHF patients with or without renal impairment showed clinical functional improvement. METHODS: A single centre, prospective but non-randomized study in 20 patients with severe congestive heart failure refractory to optimal pharmacological therapy [New York Heart Association (NYHA), class IV] was performed between 2000 and 2003. The mean age was 65.71+/-7.66 years. The patients had a baseline glomerular filtration rate of 14.84+/-3.8 ml/min. Fifteen patients were diabetics (type I, 10; type II, five). For all patients, the baseline ejection fraction was <35% (31.2+/-4.7%). The mean Charlson's co-morbidity index was 7.8+/-1.8. Patients were treated initially by 2-5 sessions of continuous veno-venous haemofiltration (CVVH) or sequential haemofiltration (SHF). Automated peritoneal dialysis (APD) was started after implantation of a Tenckhoff catheter. Three APD sessions/week (8 h each), with 15-20 l of dialysis fluid (PDF) per session (10.35+/-3.05 l of 1.5% lactated glucose and 8.95 +/-2.95 l of 4.25% glucose PDF), were performed. Total follow-up ranged between 7 and 35 months (mean 19.80+/-7.37). RESULTS: After 1 year of follow-up, all patients showed haemodynamic improvement: significant improvement of left cardiac work index (2.33+/-0.69 to 2.59+/-0.47 kg min/m(2)), reduction of the systolic times ratio (61.14+/-12.57 to 39.18+/-13.44%), lower thoracic fluid contents (0.04+/-0.005 to 0.003+/-0.0001 Omega) as well as a regression from NYHA class IV to class I. Need for hospitalization for CHF decreased from 157 to 13 days. CONCLUSIONS: Peritoneal dialysis appears to be a promising therapeutic tool for patients affected by refractory CHF. Clinical improvement of cardiac function may be related to clearing blood from middle molecular weight myocardial depressant substances, including atrial natriuretic peptide. Prospective multicentre trials are needed to confirm these encouraging results.

Aged↗
PubMed2005

Osmotic agents hamper mesothelial repopulation as seen in the doughnut in vivo model.

BACKGROUND: The problem of mesothelial cell injury derived from the use of peritoneal dialysis solutions has been explored deeply. Conversely, the eventual detrimental effects upon mesothelial cell regeneration have awaked less investigative efforts than those focused on injury. OBJECTIVE: To evaluate in the in vivo and in situ rat "doughnut" model of mesothelial repopulation, the eventual effect of peritoneal lavage with Hank's Balanced Salt Solution (HBSS) as well as that of 4.25% glucose and 7.5% icodextrin dialysis solutions. EXPERIMENTAL ANIMALS: 100 Sprague-Dawley albino rats were included in the study. Animals were divided into five groups of 20 rats each: group 1: control at zero time; group 2: sham-injected rats; group 3: rats exposed to HBSS; group 4: rats treated with 4.25% glucose peritoneal dialysis solution; group 5: rats injected with 7.5% icodextrin. METHODS: Selective exfoliation of a ring of mesothelium (width 0.8 mm, diameter 4 mm) covering the anterior surface of the liver was performed in 80 animals. The control zero-time group was used to evaluate the normal density distribution of the mesothelial cells forming the monolayer. The other groups were treated by means of daily sham injections or intraperitoneal infusion of each experimental solution for a period of 30 consecutive days. After a recovery period of 15 days, imprints and biopsies from the monolayer covering the exfoliated area were taken and processed for light microscopy. RESULTS: Macroscopic observation of the abdominal cavity at the end of the 15-day recovery period showed that the prevalence of fibrotic adhesions between the peritoneal exfoliated area and the neighboring diaphragm was 10% forthe sham-injected group, 5% for the HBSS-exposed animals, 85% for the rats injected with 4.25% glucose, and 95% for the icodextrin-treated group. Prevalence of fibrous adhesions in sham-injected animals and rats exposed to HBSS were devoid of statistically significant differences. Conversely, comparison of these groups with results observed in animals treated with the osmotic agents was significant, at the p < 0.0039 level. Regarding density distribution of mesothelial cells observed in imprints, there were no significant differences between the control zero-time and the sham-injected group. This parameter was marginally lower (p < 0.05) in the HBSS-treated rats. Imprints were not taken from animals exposed to glucose or icodextrin because a dense layer of connective tissue replaced the exfoliated mesothelial area. CONCLUSIONS: Observations made in this study support the contention that both osmotic agents, 4.25% glucose and 7.5% icodextrin, substantially restrain the normal process of mesothelial cell repopulation and induce repair by means of connective tissue. The underlying mechanism is most likely sustained oxidative stress.

Animals↗
PubMed2004

Acute oxidative stress induces peritoneal hyperpermeability, mesothelial loss, and fibrosis.

We explored the acute and long-term effects of short-lived, intense oxidative stress on peritoneal permeability and structure, induced with intraperitoneal injection of the oxidant agent deoxycholate, in rats. Ten minutes after the experimental intervention, peritoneal dialysis, performed over an exposure time of 60 minutes, revealed an increased urea dialysate/plasma ratio, greater glucose absorption, increased albumin losses in the effluent dialysate, and a reduced ultrafiltration rate. Mesothelial-cell imprints taken from the anterior liver surface indicated a substantially decreased density in the cell population. After the recovery period of 30 days, all alterations were still evident. Additionally, macroscopic and histologic observations made at this time interval detected peritoneal fibrosis and sclerosis, characterized by peritoneal adhesions, wrapping of intestinal loops, and the presence of a layer of fibrous tissue dressing the cavitary aspect of the liver peritoneal envelope. This report describes a reproducible experimental model of peritoneal fibrosis induced by acute oxidative injury. On the basis of these findings, it may be speculated that functional and structural alterations observed in patients are related to long-term continuous exposure of the monolayer to oxidative injury resulting from the high concentrations of d-glucose present in peritoneal dialysis solutions.

Acute Disease↗
PubMed2003

Icodextrin-induced lipid peroxidation disrupts the mesothelial cell cycle engine.

Fluids commonly used for peritoneal dialysis hold poor biocompatibility vis a vis the peritoneal membrane, basically due to the presence of osmotic agents. When rat mesothelium was exposed to glucose-enriched dialysis solutions for 2 h in vivo, an early and short-lived acceleration of cell life cycle was observed, which, after 30 d of exposure, resulted in a depopulated monolayer of senescent cells. These changes appear to result from persistent oxidative stress due to continuous exposure to high concentration of glucose and to substances generated by the Maillard reaction. Long-term exposure (30 d) of the peritoneal mesothelium to 7.5% icodextrin resulted in a depopulated monolayer consisting mostly of senescent cells, which, additionally, showed atypical nuclear changes and atypical mitosis suggesting DNA damage. These changes coincided with substantial lipid peroxidation, starting immediately after the introduction of the icodextrin solution into the rat's abdominal cavity. So far, the currently used osmotic agents in peritoneal dialysis fluids induce substantial oxidative injury to the exposed monolayer in vivo. Use of high concentrations of glucose results in premature senescence of the exposed cell population. The 7.5% icodextrin dialysis fluid induces through lipid peroxidation substantial genomic damage, which, in turn, sets the biological mechanisms leading to protective cellular suicide in motion.

Animals↗
PubMed2002

Peritoneal transport after long-term exposure to Icodextrin in rats.

BACKGROUND: Icodextrin, an effective osmotic substance that has been proposed as an alternative agent for peritoneal dialysis induces ultrafiltration over long dwells. This study examines the peritoneal transport after exposure to Icodextrin in rats. METHODS: Animals were divided in 4 groups and injected daily for 30 days with Icodextrin 7.5 % (n = 14), Glucose 4.25 % (n = 19) or glucose 4.25% plus Icodextrin 7.5 % (n = 13). Rats of the control group (n = 15) were not exposed. A 4-hour permeability study was performed using glucose at days 1, 30 and 60. At days 2, 31 and 61 the same animals were injected with Icodextrin. RESULTS: Slopes of effluent sodium at day 30 were significantly higher (p < 0.001) in the glucose (0.006 +/- 0.016), Icodextrin (0.013 +/- 0.014) and mixed groups (0.012 +/- 0.017) than in the control group (-0.041 +/- 0.021). Urea D/P ratio was not significantly different in the 4 groups. After 30 days, glucose effluent levels were significantly lower (p < 0.001) in the glucose (701 +/- 278 mg/dl), Icodextrin (552 +/- 209 mg/dl) and mixed groups (587 +/- 344 mg/dl) than in control rats (1519 +/- 413 mg/dl). Effluent protein (mg/l) in the mixed group (1,555 +/- 357) was significantly higher (p < 0.001) than control (376 +/- 33), glucose (1,015 +/- 232) and Icodextrin (765 +/- 75) groups at day 30. CONCLUSION: The long-term use of Icodextrin does not affect small molecule transport, but induces changes in the peritoneal protein excretion, especially when Icodextrin and glucose are injected together.

Albumins↗
PubMed2002

Mesothelial dysplastic changes and lipid peroxidation induced by 7.5% icodextrin.

BACKGROUND: The issue of icodextrin biocompatibility is somehow ambiguous. Whereas some experimental data point at better bicompatibility of icodextrin compared with high glucose concentration fluid, other reports showed substantial cytotoxic effects upon monocytes and cultured mesothelial cells. The present investigation exposes the first attempt to investigate the biocompatibility issue in an in vivo and in situ setup. METHODS: Mice were intraperitoneally injected once a day with the 7.5% icodextrin solution, during 30 consecutive days. Imprints of the mesothelial monolayer covering the anterior liver surface were taken after 2 h, 15 and 30 injections, as well as after recovery periods of 7, 30 and 60 days. Changes on the cell population were evaluated as a function of: density, cell surface area, cell radius, nuclear surface area, number of nucleoli per nucleus, nuclear cytoplasmic index, as well as for prevalence of multinucleation, mitosis, non-viable cells and apoptotic bodies. Additionally, peritoneal dialysis was performed in 3 groups of rats exposed to 4.25% glucose dialysis fluid, 1.1% amino acids solution, or to 7.5% icodextrin. Samples were taken for thiobarbituric acid reactive substances (TBARS) from each group. RESULTS: Mesothelial cell populations of mice exposed to 7.5% icodextrin displayed significantly reduced density, increased cell size, higher increased nuclear/cytoplasmic index, increased numbers of heterogeneous nucleoli, extremely low prevalence of mitosis, atypical mitosis, micronuclei, reduced cell viability as well as a significantly higher prevalence of apoptosis. Rats exposed to the same experimental solution showed significantly higher levels of TBARS (basically malondialdehyde), testifying for an undergoing process of lipid peroxidation. CONCLUSIONS: Overall, these results suggest that the 7.5% icodextrin dialysis solution induced, through a mechanism of lipid peroxidation, substantial DNA injury, leading the exposed monolayer to commit protective cellular suicide. Consequently, this information raises some doubts about the safety of 7.5% icodextrin solution in peritoneal dialysis patients.

Animals↗
PubMedDate not supplied

Iron deficiency is a common cause of anemia in chronic kidney disease and can often be corrected with intravenous iron.

BACKGROUND: There is some epidemiological and clinical evidence that the anemia seen in chronic kidney disease (CKD) in patients not on dialysis could be due to a significant extent to iron deficiency, and that adequate iron replacement could cause a marked improvement in the anemia even without the use of erythropoietin (EPO). The purpose of this work was to study the effects of intravenous (i.v.) iron administration (ferric gluconate - Ferrlecit) on hemoglobin (Hb) of patients with CKD. METHODS: Forty-seven consecutive patients with CKD with Hb <12 g/dL in whom no underlying cause for the anemia could be found underwent sternal bone marrow biopsy and had their red cell and blood iron parameters measured. They then received 250 mg of ferric gluconate (Ferrlecit) intravenously twice monthly for 3 months, and had their blood parameters measured 1 month later. No patient received erythropoietin (EPO). RESULTS: Forty-six patients had no evidence of any iron deposits in the bone marrow - consistent with the presence of severe iron deficiency. The mean serum ferritin and %transferrin saturation prior to treatment were 235.9 +/- 54.3 ug/L and 13.5 +/- 4.1%, respectively, and both increased significantly with the iron treatment. Mean Hb increased from 10.16 +/- 1.32 to 11.96 +/- 1.52 g/dL, an increase of 1.80 +/- 1.72 g/dL (p<0.01). Twenty-six patients (55.3%) reached the target Hb of 12 g/dL. Ten patients (21.3%) had an increase of 0.1-0.9 g/dL, nine patients (19.1%) had an increase of 1-1.9 g/dL and 23 patients (48.9%) had an increase of >or= 2 g/dL. CONCLUSIONS: Iron deficiency is frequently seen in anemic CKD patients not on dialysis and its correction with i.v. iron will often cause a marked increase in the Hb level, and the achievement of the target Hb of 12 g/dL even without EPO.

Aged↗
PubMedDate not supplied

Agents that modulate peritoneal membrane structure and function.

Extensive experience with chronic peritoneal dialysis has identified a series of functional and anatomical pathologic changes in the peritoneal membrane thought to be the result of repeated insults from bioincompatible solutions. Laboratory and clinical findings from recent investigations often conflict and are difficult to interpret due to variations in methodologies, animal models, study designs, and data analyses. The principal pathophysiologic mechanisms identified thus far are oxidative stress, inflammation, and their consequences. Many substances used to neutralize the action of these insults, prevent formation of toxic compounds, or directly alter solute and water transport to improve peritoneal membrane performance have been studied. We herein review the most promising of these substances or those that deserve attention because their use has contributed to better understanding of peritoneal pathophysiology. Most peritoneal solution additives have proved useless due to their toxicity and undesirable effects, ineffectiveness, or manufacturing limitations. A few substances deserve more attention, particularly those capable of restoring negatively charged membrane sites, those that somehow improve permselectivity, scavengers of oxidants, and advanced glycation end-product inhibitors and breakers. Recent publications on clinical experience with neutral pH, low glucose degradation product (GDP) peritoneal solutions, although few and preliminary, are most encouraging. The virtual elimination of GDPs in these novel solutions will probably preclude the need for GDP scavengers and inhibitors. Nonetheless, there is room for further significant improvement in solution biocompatibility and for compounds that may restore peritoneal function.

Animals↗