[Role of iron deficiency in erythropoietin sensitivity in dialysis patients with elevated C-reactive protein]. / Ruolo della carenza marziale sulla sensibilita' all eritropoietina nei pazienti in dialisi con proteina C reattiva elevata.

BACKGROUND: Chronic inflammation is a well-known cause of hyporesponsiveness of the bone marrow to erythropoietin (Epo). Factors which contribute to Epo resistance in the presence of inflammation include inhibition of erythroid precursor proliferation and functional iron deficiency induced by inflammatory cytokines. The specific role of iron deficiency in this clinical context, however, has not yet been clarified. METHODS: Our dialysis population consisted of 200 patients, from which 163 (91 males, mean age 67 +/- 12 years) who had been in dialysis for at least 4 (mean 62.4 +/- 71) months were selected for further study. Two groups were defined on the basis of C-reactive protein (CRP) concentrations: Group A (normal CRP < 5 mg/L; 78 patients) and Group B (elevated CRP > 15 mg/L; 43 patients). The remaining 42 patients with CRP in the range of 5 to 15 mg/L were excluded from the study. RESULTS: Erythropoietin dose and the parameter EpoDose/hemoglobin (Hb) were both greater in Group B (dose: 150 +/- 65 vs. 106 +/- 56 U/kg, p<0.001; EpoDose/Hb: 14.0 +/- 6 vs. 9.8 +/- 6, p<0.001. The two groups were stratified on the basis of transferrin saturation (tSAT) greater or less than 20%: A1 (tSAT > 20%, n = 52), A2 (tSAT < 20%, n = 26), B1 (tSAT > 20%, n = 19) and B2 (tSAT < 20%, n = 24). Erythropoietin dose and EpoDose/Hb were lower in A1 compared to A2 (dose: 96 +/- 52 vs. 124 +/- 6 U/kg, p<0.05; EpoDose/Hb: 8.4 +/- 5 vs. 12.4 +/- 7, p < 0.05), whereas in the B subgroups the variables were equally elevated (dose: 151 +/- 71 vs 142 +/- 59 U/kg, ns; EpoDose/Hb: 14.4 +/- 7 vs. 13.6 +/- 6, ns). Patients in subgroups A2 and B2 were treated with intravenous Fe gluconate 31 mg after each dialysis session for 6 months. Erythropoietin dose and EpoDose/Hb were significantly reduced only in subgroup A2 with normal CRP (dose: from 126 +/- 55 to 95 +/- 52 U/kg, p < 0.05; EpoDose/Hb: from 12.4 +/- 7 to 8.4 +/- 5, p < 0.05), whereas no improvement was observed in subgroup B2 with elevated CRP (dose: from 142 +/- 59 to 151 +/- 65 U/kg, ns; EpoDose/Hb: from 13.6 +/- 6 to 14.4 +/- 7, ns). CONCLUSIONS: Our data demonstrate that dialysis patients with CRP greater than 15 mg/L require an erythropoietin dose approximately 40% higher than patients with normal CRP, both in the presence and absence of iron deficiency. Iron therapy in patients with normal CRP and tSAT < 20% significantly improved the response to erythropoietin, but was completely ineffective in patients with increased CRP. These results suggest that functional iron deficiency plays a marginal role in resistance to erythropoietin observed in patients with elevated CRP concentrations.

[The hemodiafiltration with infusion of acetate-free dialysis fluid can modify the inflammatory response in patients "high responders" to inflammatory stimuli?]. / Il trattamento in emodiafiltrazione con infusione di liquido di dialisi (PHF acetate free) può modificare la risposta infiammatoria in pazienti già identificati come "high responders" a stimoli infiammatori?

PURPOSE: This study aimed to verify the effects of paired hemodiafiltration on-line (PHF-AF) on inflammation in patients who were "high responders" to inflammatory stimuli: elevated C-reactive protein (CRP), genetic polymorphisms influencing a low transcription for interleukin-10 (IL-10) and a high transcription for IFN-gamma. METHODS: Ten patients selected as high responders for IFN-gamma and low responders for IL-10 were included in a crossover study to compare PHF-AF and standard bicarbonate hemodialysis (BHD). At study entry and before the start of each dialysis session the following examinations were performed: CRP, albumin, fibrinogen, ferritin, transferrin, prealbumin and serum levels of IL-6, IL-10, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha). After the 1st and 3rd week of the study, the blood samples were also collected after the dialysis session. RESULTS: . There was a significant reduction in albumin and prealbumin in PHF-AF patients during the study; none of the other parameters were changed in both patient groups. CRP tended to be elevated after dialysis in both PHF-AF and BHD. While IL-6, IL-10 and IFN-gamma were unchanged during the dialysis session, there was a significant variation in TNF-alpha levels, which were increased in BHD (from 10.9 +/- 3.1 to 14.7 +/- 4.1 pg/mL; p=0.004) and reduced in PHF-AF (from 11.9 +/-2.8 to 6.3 +/- 2.2 pg/mL; p=0.0004). CONCLUSION: Although the cytokine levels were unchanged during the study in both BHD and PHF-AF, the modification of TNF-alpha during the dialysis session was considered as inflammatory significance.

Effects of a synbiotic milk product on human intestinal ecosystem.

AIMS: To investigate the effect of prolonged consumption of a synbiotic milk (Synbiotic) containing Lactobacillus acidophilus (strain 74-2, 10(7) CFU ml(-1)), Bifidobacterium lactis (strain 420, 10(7) CFU ml(-1)) and 2% inulin on colonic ecosystem in healthy humans. METHODS AND RESULTS: A group of 26 healthy subjects, aged 22-47 years, participated in a 6-week placebo-controlled dietary intervention study. After a 2-week baseline period, in which all volunteers consumed 500 ml day(-1) of 2% skimmed milk (Placebo), the study was designed as a randomized, double-blind, two-armed parallel study in which 4-week consumption of 500 ml day portions of Synbiotic or Placebo were compared. Faecal microbial counts, pH, l-lactic acid and bile acid concentrations were assessed before and after the intervention. Synbiotic consumption significantly decreased faecal dry weight (P < 0.01) and l-lactic acid (P < 0.05) concentration, while significantly increased faecal bifidobacteria (P < 0.05) and lactobacilli (P < 0.01) counts. CONCLUSION: The tested synbiotic milk showed its synbiotic nature by enhancing the growth of bifidobacteria and lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: Scientific support to functional effect of a synbiotic milk.

Transformation of sulfated bile acids by human intestinal microflora.

The in vitro transformation, under anaerobic conditions, of 3- and 7-monosulfated and unsulfated bile acids, was studied in incubates of fecal flora from three healthy subjects. Chenodeoxycholic acid 7 alpha-sulfate and ursodeoxycholic acid 7 beta-sulfate were recovered unchanged, in all cultures, at the end of the incubation time. 3-Sulfated bile acids were metabolized in a different way by the three stool specimens. During the transformation of chenodeoxycholic acid 3-sulfate, desulfation, 7-dehydroxylation and 3-epimerization were observed. In contrast, 3-epimerization was not noticed when ursodeoxycholic acid 3-sulfate and lithocholic acid 3-sulfate were metabolized, the latter being principally transformed into delta 3-cholenic acid, probably by a bacterially mediated trans-elimination of sulfate group. The results obtained seem to prove that the presence of a SO3H group in 7-position usually hinders microbial transformations, which are not affected by a sulfate group in 3-position. Moreover, the 3-sulfated bile acids proved to be less sensitive to the microbial action than the corresponding unsulfated acids, with exception of lithocholic 3-sulfate.

Antimicrobial susceptibility tests on anaerobic oral mixed cultures in periodontal diseases.

The ecosystem of the dental plaque in periodontal diseases is very complex: the study of such micro-organisms, which are mostly strict anaerobes, requires the use of specific techniques under conditions of strict anaerobiosis. The aim of the present study was to design a rapid method to evaluate the activity of antimicrobials on mixed bacterial plaque of subjects with periodontal diseases. The study was carried out using a computerised instrument generally used for simultaneous diagnostic tests with aerobic bacteria. Operative and methodological modifications were made to obtain conditions of strict anaerobiosis and the balanced growth of all the microbial forms present in the mixed cultures of the plaque. Penicillins and cephalosporins were active on all the samples, whereas colistin, gentamicin, kanamycin and nalidixic acid showed no activity. Clindamycin, tetracycline, erythromycin and penicillin G were effective only against some samples. The activity of the antimicrobials towards isolated strains was analogous to that towards the corresponding mixed culture.

Validation of a simple method for assessing sodium intake in dialysis patients.

It has been reported that sodium intake can be estimated in dialysis patients by the increment in the body sodium pool from the end of a dialysis session to the beginning of the following one. To verify the reliability of this method we compared the sodium intake, estimated by the interdialytic changes in plasma sodium concentration (C) and body water volume (V), to sodium removal during three consecutive sessions. For this purpose we investigated 9 nondiabetic patients, 5 females and 4 males, under chronic hemofiltration treatment. Sodium intake was estimated by the formula (C(pre) V(pre)) - (C(post) V(post)) using a flame photometer and electrical bioimpedance to determine the plasma sodium concentration and total body water, respectively. Sodium removal was calculated by the difference between sodium loss into the ultrafiltrate and sodium gain with the reinfusion fluid. The mean values of sodium intake calculated during the three intervals corresponded with the sodium losses measured during the three hemofiltration sessions in each patient (338+/-55 vs. 329+/-67 mEq; r = 0.92, p<0.0001). A direct relationship was also observed between sodium intake and both interdialytic body weight increase (r = 0.89, p< 0.0001) and fluid loss during the sessions (r = 0.88, p<0.0001). This data demonstrates that sodium intake can be properly estimated by the interdialytic changes in body water and plasma sodium concentrations. They also suggest that fluid intake may be influenced by sodium consumption and that sodium intake monitoring could be useful for the control of excessive interdialytic fluid gain.