Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

Participation of lipid peroxidation in the loss of hepatic drug-metabolizing activities in experimental fascioliasis in the rat

Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls; delta E 1% = 1.55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls; delta E 1% = 1.96), when the loss in the enzyme activities is maximal (MFO - 60/70%; GT - 65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability: this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation.     

The axon initial segment as a possible determinant of retinal ganglion cell dendritic geometry

In wholemounted retinae of cat, rat and monkey, in which ganglion cells were retrogradely labelled with horseradish peroxidase, a quantitative analysis of the direction of the axon initial segment with respect to the optic disc and of the relationship between the axon initial segment and the direction and distribution of primary dendrites was performed on the class of largest ganglion cells. The results show the following. (1) In all 3 species, the majority of primary dendrites of ganglion cells are directed away from the axon initial segment. (2) Primary dendrites arise with a greater frequency from the region of the cell body opposite to the axon initial segment than close to it. (3) In cat the direction of the axon initial segments show less variance in their initial direction with respect to the optic disc than in rat or monkey. In adult cats the nucleus of alpha-ganglion cells occupies a central position. In the kitten the position of the nucleus is eccentric and lies in a part of the cell body opposite to the axon initial segment. The nucleus moves to a central position over the next 3 weeks. The position of the axon initial segment is discussed as a possible determinant of ganglion cell dendritic geometry.     

Percutaneous balloon dilatation of calcific aortic valve stenosis: anatomical and haemodynamic evaluation.

Two groups of elderly patients with calcified aortic stenosis were treated by balloon dilatation. In group 1, the valve was dilated just before surgical replacement of the valve. The valvar and annular changes occurring during dilatation were examined visually. In 20 of the 26 patients in this group there was no change. In the six remaining patients mobilisation of friable calcific deposits (1 case), slight tearing of the commissure (4 cases), or tearing of the aortic ring (1 case) were seen. Dilatation did not appear to alter valvar rigidity. In 14 patients (group 2) the haemodynamic gradient across the aortic valve was measured before and immediately after dilatation and one week after the procedure. Dilatation produced an immediate significant decrease of the aortic mean gradient and a significant increase of the aortic valve area. Eight days later the mean gradient had increased and the aortic valve area had decreased. Nevertheless there was a significant difference between the initial gradient and the gradient eight days after dilatation. The initial aortic valve area was also significantly larger than the area eight days after dilatation. The aortic valve gradient rose significantly in the eight days after dilatation and at follow up the gradients were those of severe aortic stenosis.