Endothelin 1 and cyclic guanosine monophosphate in nonimmunological progression of mesangial proliferative glomerulonephritis.
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Biomedical subjects
Publications and source records attributed to G Bonetti.
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An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.
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Apo(a), the specific lipoprotein(a) (Lp(a)) apolipoprotein, is characterized by different isoforms (from 6 to 11 on SDS-PAGE) encoded by a system of autosomal codominant alleles. Electrophoresis on agarose gel displays a better resolving power than SDS-PAGE (a larger number of apo(a) isoforms is detected). The aim of this work was to set up a simple technique that uses a capillary blotting apparatus and a polyvinylidene difluoride membrane for protein transfer. We tested an Italian population sample of 202 healthy subjects (123 men and 79 women) and we detected 22 apo(a) isoforms varying from 280 to 775 kDa. In our sample, 135 subjects (66.5%) had a single-band phenotype, 64 (31.7%) had a double-band phenotype and 3 subjects (1.5%) had no detectable bands ('null' phenotype). This simple and reproducible technique could be applied in the genetic screening of apo(a) polymorphisms and for clinical investigations of the risk of developing cardiovascular diseases.
The role of malnutrition in the development of cachexia in rats bearing the Yoshida ascites hepatoma AH-130 was investigated by comparing the changes in tissue protein turnover in these animals with those observed in pair-fed controls. The tumor elicited in rats an early and conspicuous loss of body weight and tissue waste. Protein loss was particularly prominent for the gastrocnemius muscle and the heart and less pronounced for the soleus, while the diaphragm was little affected. Liver, kidneys, and spleen transiently increased in weight then regressed and eventually atrophied, while adrenals were enlarged over the whole experimental period. Protein waste was mainly due to acceleration of tissue protein breakdown, this protein hypercatabolic state being associated with increased cathepsin D activity in liver and gastrocnemius. In pair-fed animals the liver showed a marked protein loss resulting from enhanced catabolism, while the sharp decrease of heart protein content and the less prominent waste of the gastrocnemius were due to a reduction in protein synthesis. The total plasmatic concentration of free amino acids in AH-130-bearing rats was decreased at Day 4, when the tumor was actively proliferating, and returned to control values at Day 10, when the tumor had reached a stationary state. On the contrary, in pair-fed animals total plasma amino acids decreased over the whole experimental period. Plasma branched-chain amino acids were unchanged or even decreased in tumor hosts, while the Gly/Pro ratio was elevated in pair-fed rats. The intracellular concentration of free amino acids was higher in stationary than in exponentially- growing tumors, reflecting the enhanced proteolytic rates observed in stationary tumor cells. On the whole, the results suggest that reduced food uptake and metabolic competition by the tumor are not sufficient to justify the marked hypercatabolism in host tissues during the AH-130 hepatoma growth. The profound differences between tumor-bearing and pair-fed animals suggest that, if malnutrition undoubtedly played a role in this model of cancer cachexia, its effects were overwhelmed and subverted in the frame of the tumor-host interplay that dictated a distinctively peculiar syndrome.
A plasmatic concentration for each aminoacid, between 1 and 1.5 times the normal value in fasting healthy subjects, is considered as an optimal target during total parenteral nutrition (TPN) in malnourished patients. We have analyzed the correlation between the aminoacid input and the aminoacid plasmatic concentration during TPN at different aminoacid composition. By exponential regression curves we then calculated the input required to keep each aminoacid plasma concentration in the optimal range.
In 16 critically ill patients with full-blown stress reaction and without severe organ failure, we studied the kinetics of the arterial plasma amino acid (aa) profile during the first 48 h of total parenteral nutrition (TPN) in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions giving, with the same nitrogen load, different intakes of individual amino acids. We found four different responses to the administered amino acids. Some amino acids showed a different trend depending on the dose given. At lower doses a steady state was achieved sooner. Plasma levels of amino acids not supplied in the TPN were unaffected or decreased, achieving a steady state at various times during the study period. We conclude that, in critically ill patients, stable arterial plasma amino acid concentrations are obtained within 24 h of starting TPN. In such patients, valid studies of the effect of amino acid solutions may therefore be carried out over short periods of time, thereby minimizing errors due to a fluctuating and unstable clinical state.
Ten-three patients were investigated during the early postoperative phase after orthotopic liver transplantation to assess the adequacy of the amino acid (AA) supply during both parenteral (days 1-5) and enteral (days 6-9) nutrition. Plasma AA profile was determined preoperatively, on day 4 and 5 during TPN and on day 8 and 9 during EN, urea production rate was measured every day. Calories input was 28 kcal.kg-.day as glucose, nitrogen intake was 0.25 g.kg- day, supplying individual AA on the basis of previous studies. Urea nitrogen production during TPN (9-11 gN/m2.day) outlines the ability of the transplanted liver to manage the overall nitrogen load. Individual AA plasma profile was considered the expression of an adequate input when comprised between 1 and 1.5 times the normal value, in this respect we obtained adequate levels of all essential AAs. Particularly phenylalanine, methionine and branched chain AA, critical during liver failure, were kept in this range by supplying 68, 48 and 500 mg.kg-1.day. According to AA profile the supply of cystine and tyrosine (conditionally essential AAs), and of histidine, taurine, proline and serine could be safely increased. Not given dispensable AAs (glutamine, asparagine, citrulline and alfa amino butyric) showed a plasma level below the norm and should be added to the diet.
The authors report a case of extrinsic stenosis of the sigmoid colon due to inflammation of the uterus and adjoining parts. Attention is drawn to the possibility that the radiological images of this condition may be similar to neoplastic diseases.
The equilibrium kinetic of two different amino acid solutions was investigated in ten catabolic patients (Parentamin, Pierrel; HBC, Baxter). Plasma amino acid pattern was determined on arterial samples before TPN and several times over 48 hours of TPN. Nitrogen balance was measured from 24 hours urine collection. Three different cinetic trends were found: a fast modification (diminution or increase), a slow adaptation, or no modification of plasmatic levels, however each amino acid reached a steady state plateau. The adequacy of the infusion of each amino acid was evaluated comparing its steady-state plasma level to the after lunch level in healthy man. This made possible to approximate metabolic needs of each of the infused amino acids and to identify the inadequacy of some metabolic pathways to synthetized non essential amino acids lacking in solutions. This made possible to identify amino acids infused in excess or in defect, and those infused in dose adapt to the metabolic needs of such patients.
A young male from Apulia region (Southern Italy), heterozygous carrier of Hb-J Calabria (beta 64(E8) Gly-Asp), was described here. He showed mild polycythemia, and his whole blood dissociation curve for oxygen was clearly left-shifted, with a decreased p50. But these characteristics were not only due to the hyperaffinity of the abnormal pigment, accounting for about one third of the total Hb; in fact, also Hb-A, the main pigment present, had relative hyperaffinity. Nevertheless, this subject was completely symptomless, suggesting that the abnormal Hb was almost completely excluded from respiratory exchange and traveled always oxygenated also in the venous-capillary bed. However, the level reached by Hb-A furnished a satisfactory functional compensation against tissue hypoxia.
Body N balance, 3-methylhistidine (MEH) excretion, amino acid (AA) plasma concentration, and fluxes across the leg were investigated both during fasting and during parenteral nutrition of injured patients in order to better understand protein-sparing mechanisms induced by metabolic support in the whole body and in skeletal muscle. Patients were randomized to receive 15 or 30 kcal/kg.day coupled with 0.30 g of N either with standard or branch-chain (BC)-enriched AA solutions. During fasting, patients were highly catabolic (N balance -14.7 +/- 1.2 g N/m2.day, MEH excretion 422 +/- 25 mumol/m2.day) and showed a high efflux of AA N from the leg (5.08 +/- 2.1 g N/m2.day) without difference between the groups. During treatment, body N balance (-5.55 +/- 0.88, p less than .001) and MEH excretion (284 +/- 20, p less than .001) were significantly reduced without difference among the groups; also, AA N leg efflux (2.64 +/- 0.47, p less than .001) was reduced. Moreover, considering the effect of calorie load, patients receiving 30 kcal/kg.day showed a lower efflux of total AA N and of some AA considered as markers of muscle protein catabolism, such as phe, lys, met, and glu. The main difference between solutions was in the efflux of BCAA; particularly, val and leu efflux was turned into uptake in the BCAA group. No significant difference among the groups was found in N balance and MEH excretion during treatment. In brief, muscle catabolism was reduced in an amount dependent on glucose and insulin load, but it was not influenced by BCAA supply. Whole body net protein catabolism was reduced through different mechanisms, either an increased visceral N retention or a decreased muscle N loss. However, muscle N loss was never abolished even in the high calorie groups.
Functional parameters of the whole blood oxygen loading from 66 anemic subjects, compared with those from 66 normal adult of both sexes display the following behaviour: a) Adult males and females differ for p50 values, which are higher in females because of their lower Hb level. This difference is already well known and appears to be statistically significant. b) The same difference is amplified in anemic subjects, where also pH lowering contributes to the right-shift of p50. c) The inverse relationship between p50 and DPG values differs if analysed at the actual pHs, at pH corrected at 7.4, or extrapolated from Bohr effect. In fact, the three relative plots do not parallel, and their most significant intersects drop around 0.8-0.9 value of DPG, and 26-27 torr of p50, i.e. within normal limits.
The main functional parameters of blood stored at +4 degrees C in ACD, according to the common transfusional practice, have been carefully followed in the course of 40 days. The expected depletion of DPG takes place within 10 days, but apparently, no increase of the Hb affinity towards oxygen is observed in this period (or later), because pH lowering acts in the opposite direction during the same time. However, the intrinsic increased affinity of Hb is promptly revealed if the "actual" pHs are corrected at the standard value of 7.4, and/or are extrapolated at this pH from Bohr effect.
The metabolic derangements of injury are known to influence nitrogen (N) requirements whilst less is known about individual amino acid (AA) requirements. This study was designed to investigate prospectively N vs AA requirement in 36 injured patients treated with total parenteral nutrition (TPN). The non-protein caloric input was 30 kcal kg-1 day-1 and three AA solutions were assessed containing the same AAs but in different proportion. Overall N intake was set at 0.35 g N kg-1 day-1 for solution A and B and 0.24 g N kg-1 day-1 for solution C. Solution B was similar to A, both being enriched in branched chain AAs (BCAA: 0.69 g kg-1 day-1 in B compared with 0.55 g kg-1 day-1 in A) while decreased in aromatic and sulphurated forms (1.75 times the normal need). Solution C was designed to maintain a daily input of BCAA similar to A (0.52 g kg-1 day-1) but with the supply of aromatic and sulphurated AA between solutions A and B, the supply of other AAs (lysine, theonine, histidine, arginine, glycine) being dependent on the selected N intake. For all the essential AAs the supply was always greater than normal allowances. Increasing BCAA over 0.55 g kg-1 day-1 did not improve N balance when N intake was 0.35 g kg-1 day-1, whilst nutrition with solution C was unable to maintain N balance. Moreover we found indirect evidence that this N intake, 0.52 g kg-1 day-1 was more sparing than 0.37 g kg-1 day-1 of BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of major trauma and sepsis on skeletal muscle, central tissue and whole body nitrogen (N) metabolism was investigated in 5 patients before and during TPN (30 kcal, 0.30 g N kg-1 day-1). Fasting 3-methylhistidine (MEH) urinary excretion was elevated (407.9 +/- 67.6 mumol m-2 day-1), muscle and body N balances (NB) were markedly negative (-28.2 +/- 4.6 g m-2 day-1 and -15.7 +/- 3.1 g m-2 day-1), while central tissue NB was positive (13.0 +/- 2.4 g m-2 day-1). TPN effected a reduction in MEH excretion (261.8 +/- 27.5 mmol m-2 day-1 - p less than 0.05) and decreased the release of almost all amino acids from muscle tissue, some of them acting as catabolic markers. Muscle (-7.2 +/- 1.2 g m-2 day-1 - p less than 0.01) as well as body NB (-4.8 +/- 1.4 g m-2 day-1 - p less than 0.01) improved, whilst central tissue NB worsened, even though still positive (3.1 +/- 1.6 g m-2 day-1 - p less than 0.05). Gathering fasting and TPN data MEH excretion was significantly related to both body (r = 0.89) and muscle (r = 0.73) NB, that were highly related to each other (r = 0.93), being muscle always worse than body NB. In conclusion, the anticatabolic activity of TPN is confirmed, although our setting did not achieve muscle NB, it was consistently improved and seems to be the major determinant of body NB, in contrast central NB and central N utilization (46.4% +/- 5.4 vs 15.8% +/- 8.4 - p less than 0.05) worsened.
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