Cardiovascular risk factors in severe chronic renal failure: the role of dietary treatment.

BACKGROUND: Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF). METHODS: Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid. RESULTS: Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p < 0.005) with a reduction of LDL cholesterol (p < 0.01) and an increase of apoA1/apoB ratio (p < 0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p < 0.05) with lower TBARS concentrations (p < 0.01) and a significant reduction of total homocysteine (p < 0.002), Lp(a) (p < 0.002) and CRP levels (p < 0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p < 0.001) and OxLDL (p < 0.006) were associated to a risk of CRP > 0.3 mg/dl. CONCLUSIONS: These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Variation in genome organization of the plant pathogenic fungus Colletotrichum lindemuthianum.

The genome structure of Colletotrichum lindemuthianum in a set of diverse isolates was investigated using a combination of physical and molecular approaches. Flow cytometric measurement of genome size revealed significant variation between strains, with the smallest genome representing 59% of the largest. Southern-blot profiles of a cloned fungal telomere revealed a total chromosome number varying from 9 to 12. Chromosome separations using pulsed-field gel electrophoresis (PFGE) showed that these chromosomes belong to two distinct size classes: a variable number of small (< 2.5 Mb) polymorphic chromosomes and a set of unresolved chromosomes larger than 7 Mb. Two dispersed repeat elements were shown to cluster on distinct polymorphic minichromosomes. Single-copy flanking sequences from these repeat-containing clones specifically marked distinct small chromosomes. These markers were absent in some strains, indicating that part of the observed variability in genome organization may be explained by the presence or absence, in a given strain, of dispensable genomic regions and/or chromosomes.

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells.

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

FLAG (fludarabine, cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: in vitro and in vivo effects.

Thirteen consecutive adult patients with primary refractory (n = 5) or relapsed (n = 8) acute lymphoblastic leukemia (ALL) were treated by an induction schedule (FLAG) consisting of Fludarabine (30 mg/sqm/d) plus high dose Cytarabine (HD-ara-C: 2 g/sqm/d) (d 1-5) and G-CSF (from d O to polymorphonuclear recovery). Patients achieving complete remission (CR) were administered a second FLAG course as consolidation and were then submitted to an individualized program of post-remission therapy, depending on the patient's age and performance status. CR was achieved in 8/12 evaluable cases (67%). The median CR duration was 22.5 w. CR attainment was significantly related to the co-expression of lymphoid and myeloid antigens. ALL/My+ patients achieved CR in 6/6 evaluable cases vs. 2/6 for ALL/My+. In vitro 3H ara-C incorporation into cellular DNA resulted significantly increased by Fludarabine (in 7/9 tested cases) and, furthermore, by the association of Fludarabine G-CSF in 5 evaluable ALL/My+ cases; in contrast, no effect of G-CSF addition to Fludarabine was observed in 4 ALL/My. Myelosuppression was observed in all patients: the median time to neutrophils > 0.5 x 10(9)/1 was 16.3 d (range 13-22) and 16.2 d (range 9-29) to platelets > 20 x 10(9)/1. Nonhematological toxicity was minimal. In conclusion, FLAG is an active and tolerable combination in refractory ALL, particularly in cases with myeloid antigen expression where G-CSF appears to improve efficacy, probably increasing ara-C incorporation into the DNA of leukemic cells.

Life span of circulating membrane CD4 inserted into the plasma membranes of autologous red blood cells of HIV-infected subjects.

Membrane recombinant CD4 was electroinserted into the plasma membrane of red blood cells (RBCs) from four HIV patients. CD4 had been labeled with 125I before electroinsertion. The RBCs-CD4-125I were labeled with 51Cr and autotransfused to the donor patients. The hematological indexes and the P50 value of the RBCs were not modified by the electroinsertion of CD4. The life span of the RBCs was not affected by electroinsertion of CD4 (t1/2 approximately 30 days), whereas the exposed CD4 showed a kinetics of disappearance characterized by two half-life times: a short one (t1/2 approximately 1 day) and a long one approximately equal to that of the RBCs. No side effects or anti-CD4 immune responses were observed in patients over a period of 28 days. The RBC-CD4 entity appears to be long-lived and has no adverse effect in HIV patients.

Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases.

Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations). The compound was administered intravenously by 6-hour infusion at a dose of 5 microgram/kg/day until the patient reached at least 1000 PMN in the peripheral blood. Eleven out of the 13 evaluable patients showed a significative improvement in hemopoietic recovery, even though in CHT patients hematological reconstitution was higher in terms of PMN counts. The ABMT patients, however, showed a faster myeloid recovery than that obtained both in a group of 14 NHL and in a series of 8 MM previously submitted to ABMT in our Institution. Moreover the increase in peripheral neutrophils appeared to be stable, since it was maintained throughout one month after the end of rhGM-CSF therapy. We did not observe effects on platelet or erythrocyte recovery. We conclude that rhGM-CSF is active in accelerating the recovery of myelopoiesis, without significant toxic or collateral effects.