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Biomedical subjects

C Manzoni

Publications and source records attributed to C Manzoni.

At least 37 records · Page 2Linked to original sources
PubMed2000

Relevance of the conductivity kinetic model in the control of sodium pool.

Changes in the body sodium pool caused by dialytic treatment have very important clinical implications, mainly in terms of intradialytic cardiovascular instability and interdialytic hyperhydration and hypertension with long-term cardiac hypertrophy and dilation. A kinetic model could be helpful in order to define the dialysate sodium concentration needed to match intradialytic hydrosodium removal with interdialytic sodium and water intake, but unfortunately, none of the sodium kinetic models are suitable for routine clinical application. Two conductivity kinetic models (one for hemodialysis and one for paired filtration dialysis) have been developed on the basis of the linear relationship between the sodium content and conductivity of every saline solution and plasma water and according to basic theory for ionic dialysance determination. These models make it possible to know at the start of each session the dialysate conductivity needed to obtain the desired final plasma water conductivity or to know the latter when the former is known. Clinical evaluations showed that conductivity kinetic models are very precise and accurate and may be used instead of sodium kinetic models. Furthermore, they are suitable for routine use because they do not require blood sampling or laboratory determinations. Clinical application of the conductivity kinetic model has shown that the reduced variability of end-dialysis plasma water conductivity obtained when using the model to identify dialysate conductivity significantly reduces cardiovascular instability, even without any changes in average sodium removal. Given that ionic dialysance can be easily, inexpensively, and repeatedly measured at each dialysis session, it seems realistic to expect that conductivity kinetic modeling will soon become a part of everyday clinical practice.

Blood Pressure↗
PubMed2000

Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells.

The activation of LDL receptors was described recently in a human hepatoma cell line (Hep G2) exposed both to alpha + alpha' subunits from 7S soy globulin and to Croksoy(R)70, a commercial isoflavone-poor soy concentrate. To assess the final identity of the peptide(s) putatively responsible for the biochemical effect, experiments were performed in Hep G2 cells, exposed either to synthetic peptides corresponding to specific sequences of 7S soy globulin or to peptides from the in vitro digestion of Croksoy(R)70. Moreover, the ability of the whole 7S globulin, its subunits and whole Croksoy(R)70 to interfere in the apolipoprotein B (apo B) secretion in the medium as well as in sterol biosynthesis was evaluated in the same model. Increased (125)I-LDL uptake and degradation vs. controls were shown after Hep G2 incubation with a synthetic peptide (10(-)(4) mol/L, MW 2271 Da) corresponding to positions 127-150 of the 7S globulin. Cells exposed to Croksoy(R)70 enzyme digestion products showed a more marked up-regulation of LDL receptors vs. controls, compared with vs. Hep G2 cells incubated with undigested Croksoy(R)70. Among soy-derived products, only the 7S globulin inhibited apo B secretion and (14)C-acetate incorporation when tested in Hep G2 cells at a concentration of 1.0 g/L. These findings support the hypothesis that if one or more peptides can reach the liver after intestinal digestion, they may elicit a cholesterol-lowering effect. Moreover, the protein moiety, devoid of isoflavone components, is likely to be responsible for this major biochemical effect of soy protein.

Amino Acid Sequence↗
PubMed2000

Removal of small and middle molecules by convective techniques.

The current renewed interest in haemofiltration (HF) is due mainly to its potential advantages in reducing morbidity and mortality. We analysed the data obtained from eight patients treated with pre-dilution HF and compared them with the calculated post-dilution HF and haemodialysis (HD) data in order to quantify the depurative performance of HF and to assess whether its claimed ability to improve cardiovascular stability is at least partially related to less sodium removal. The urea clearance (as a marker of small molecules) of pre-dilution HF was equivalent to that of standard low-flux HD and approximately 20% higher than that of postdilution HF. For a calculated increase of 117% in the dialytic clearance of beta2-microglobulin using high-flux HD, the increase in beta2-microglobulin removal with HF was only 30%. The intradialytic decrease in plasma water beta2-microglobulin concentrations was 73% (vs 53% in HD) followed by a post-dialytic rebound of 85% (vs 42% in HD). The interdialytic concentrations of beta2-microglobulin were always lower. At the start of the subsequent session, the beta2-microglobulin concentrations observed in HF-treated patients were 92% of those in the patients treated with HD. Sodium removal was similar using both HF modalities at the same total dialysate and reinfusate sodium concentrations, and lower than in the case of HD. HF makes it possible to obtain constantly lower plasma water beta2-microglobulin concentrations whose long-term clinical relevance has to be verified. Under usual operational conditions, sodium removal is less with pre-dilution HF than with HD, thus raising some doubts about the intrinsic capacity of HF to improve cardiovascular stability by a mechanism other than less sodium removal.

Hemofiltration↗
PubMed2000

Treatment modalities in comparison: when do clinical differences emerge?

BACKGROUND: Despite technological advances in dialysis equipment and modalities, the survival, morbidity and quality of life of uraemic patients undergoing regular haemodialysis treatment are still severely affected by acute intradialysis and long-term complications, possibly related to the treatment itself. Convective treatment modalities, such as haemodiafiltration and haemofiltration, are thought to be further improvements over standard diffusive haemodialysis. Moreover, several of the pathways activated in patients during dialysis have the potential to produce many side-effects. These occur three times a week, and are particularly intense in patients dialysed with so-called 'bio-incompatible' membranes. Thus the biocompatibility of dialysis membranes is increasingly recognized as one of the main factors in the improvement of dialysis treatment. METHODS: The main clinical studies to date are reviewed to highlight the clinical effects of different treatment modalities and membranes on the most important acute and long-term haemodialysis-related complications. RESULTS: Epidemiological studies suggest that semisynthetic and synthetic membranes may reduce morbidity and mortality in dialysis patients. Despite the proven biological superiority of biocompatible membranes, we lack definitive evidence that thrice-weekly complement and cell activation over a period of years is detrimental to patients, because the results of prospective randomized studies are conflicting. However, it is important to remember that factors other than the dialysis membrane could influence the 'biocompatibility' of dialysis, including the dialysate, dialyser geometry, the distribution of blood in the dialyser, reuse, the sterilizant and materials used in reprocessing. CONCLUSIONS: Further large-scale prospective and randomized trials with a long follow-up are needed in order to better clarify the clinical effect of different treatment modalities on the morbidity and mortality of patients on chronic renal replacement therapy. In particular, it must be clarified whether the possible clinical differences in treatment modalities are based on differences in the clearance of middle molecules or on biocompatibility, or, more generally, on the increasingly recognized clinical importance of high-flux treatments, and the possible interaction between membrane flux and biocompatibility.

Anemia↗
PubMed2000

Blood flow distribution in sorbent beds: analysis of a new sorbent device for hemoperfusion.

A new polymer-based sorbent cartridge has been recently developed for enhancing middle molecule removal during hemodialysis. The cartridge (Betasorb, Renaltech, New York, USA) has been designed to be placed in series with the dialyzer in the blood circuit. It is therefore important to evaluate the distribution of flow into the blood compartment of the device in order to assess if the surface of the sorbent is utilized to the best. For this purpose, a special imaging technique was utilized. Cartridges were analyzed during a simulated in vitro circulation at 250 and 350 ml/min of blood flow and 25% and 40% hematocrit. Cartridges were placed in vertical position and a cross longitudinal section 1 cm thick was analyzed in sequence by a helical scanner. Dye was injected into the arterial inlet and the progressive distribution was evaluated by sequential densitometrical measures carried out automatically by the machine. The sequential images analyzed by the scanner demonstrated excellent distribution of the flow in the blood compartment with minimal difference between the central and the peripheral regions of the compartment. In particular the following flow velocity pattern could be observed under the different experimental conditions tested. We may conclude that the cartridge design is adequate and no channelling effects could be detected in the blood compartment. The flow distribution is slightly affected by changes in flow rate and hematocrit showing an optimal utilization of the available surface for molecule adsorption.

Adsorption↗
PubMed1999

Biochemical and pharmacological evidence of a functional role of AMPA receptors in motor neuron dysfunction in mnd mice.

We studied ionotropic glutamate receptor subtypes and the effect of chronic treatment with NBQX [6-nitro-7-sulphamoyl-benzo(F)quinoxaline-2,3-dione], a selective (rs)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, in the spinal cord of mnd mice. NBQX (8 mg/kg daily i.p. for 3 weeks starting from 24 weeks old) significantly improved the behavioural scores (hind leg extension reflex, cage rung grasping and gait) in mnd mice, measured after the last drug injection, and increased the number of mice with 'normal' gait (from 50% to 90%, P < 0.05). Receptor binding autoradiography of the competitive N-methyl-D-aspartate (NMDA) antagonist, [3H]CGP 39653, of [3H]AMPA and [3H]kainic acid in spinal cord sections, measured after 1 week of drug washout, were not significantly different in control and mnd mice, and were not modified by NBQX. GluR2/3 immunoreactivity, assessed using Western blotting, was significantly enhanced (by 59%, P < 0.01) in the spinal cord but not in the brain of 28-week-old mnd mice compared to age-matched control mice. NBQX treatment increased GluR2/3 immunoreactivity in the spinal cord of control mice and mnd mice by 327 +/- 74% (P < 0.01) and 212 +/- 52% (P < 0.01), respectively. The changes in GluR2/3 subunits may involve adaptive mechanisms of the receptor and play some role in the protective effect of NBQX. These findings suggest that selective antagonism of ionotropic non-NMDA receptors may be of value in the treatment of motor neuron disease.

2-Amino-5-phosphonovalerate↗
PubMed1999

On-line monitoring and convective treatment modalities: short-term advantages.

BACKGROUND: Despite technological advances in dialysis equipment, the morbidity and quality of life of uraemic patients undergoing regular haemodialytic treatment are still severely affected by acute intradialytic complications possibly related to the treatment itself. Cardiovascular instability still affects >30% of dialytic sessions and, although its pathogenesis is multifactorial, dialysate sodium concentration (and, consequently, intradialytic sodium removal) is one of the main factors affecting intradialytic hypotension. Convective treatment modalities and so-called biocompatible membranes increasingly are recognized as improving acute and particularly chronic dialytic complications because a number of the pathways activated in patients during dialysis with 'bioincompatible' membranes have the potential to produce many side effects. METHODS: The main clinical studies are reviewed to highlight the advantages of on-line monitoring and convective modalities on acute intradialytic symptoms. RESULTS: The conductivity kinetic model has been shown to be a reliable and inexpensive method of matching intradialytic sodium removal and interdialytic load. By applying this model to patients prone to dialysis hypotension, a smaller reduction in intradialytic systolic blood pressure has been observed, without any change in dialysate and reinfusate sodium concentrations or dry body weight. Furthermore, a new model of haemodialysis potassium removal based on a decreasing intradialytic potassium concentration and a constant plasma-dialysate potassium gradient is capable of reducing the arrhythmogenic effect of standard haemodialysis. Despite the proven biological superiority of biocompatible membranes, there is no definitive evidence that membrane biocompatibility and/or flux lead to a decrease in acute intradialytic clinical symptoms. CONCLUSIONS: On-line monitoring of intradialytic sodium removal and the potassium gradient is capable of reducing intradialytic hypotension and the arrhythmogenic effect of haemodialysis, and thus having a considerable clinical impact on acute intradialysis complications. As far as the effects of biocompatibility and/or flux on the incidence of acute intradialytic clinical symptoms are concerned, further trials involving a sicker patient population with higher prevalence of intradialytic hypotension are needed in order to achieve statistical power.

Cardiovascular System↗
PubMed1998

Spinal cord GLT-1 glutamate transporter and blood glutamic acid alterations in motor neuron degeneration (Mnd) mice.

This study characterizes for the first time neurochemical mechanisms in Mnd mice, initially described as a model of motor neuron disease and more recently proposed as a model for neuronal ceroid lipofuscinosis. A selective decrease (-30%) of [3H]glutamate uptake was found in spinal cord but not cortical synaptosomes of Mnd mice aged 28 weeks, when they show histopathological alterations, complete blindness and moderate neurological deficits. In spite of the widespread presence of stored material in neurons in many brain regions and spinal cord, the active transport of [3H]serotonin, [3H]dopamine and depolarization-induced [3H]serotonin release were not affected. Spinal EAAC1 glutamate transporter protein was significantly decreased in some but not all aged mice by 36% on average, possibly due to the loss of motor neurons. GLT-1 immunoreactivity was reduced by 34% in 28-week-old Mnd mice, while GLAST immunoreactivity was not affected. In Mnd mice aged 14 weeks, when there was no apparent alteration of motor function, the defect in the glial transporter protein GLT-1 was similar to that in 28-week-old mice (25%). Blood glutamic acid concentration was increased in Mnd mice aged 14-22 weeks. We suggest that the early decrease of GLT-1 protein might raise the extrasynaptic glutamic acid concentration, and contribute to the loss of motor neurons in affected mice, resulting in low [3H]glutamate uptake, low EAAC1 immunoreactivity and neurological deficits.

ATP-Binding Cassette Transporters↗
PubMed1998

Proteins of rat serum: I. Establishing a reference two-dimensional electrophoresis map by immunodetection and microbore high performance liquid chromatography-electrospray mass spectrometry.

In the present investigation, we have identified 56 major spots, or spot rows, corresponding to 22 proteins, in the 2-DE pattern of adult male rats. This was done mainly by applying two complementary techniques, namely immunoblotting and high performance liquid chromatography-mass spectrometry (HPLC-MS) peptide mapping. Glycoproteins were characterized by affinity blotting with six lectins. We have also detailed how rat serum differs from human serum in two main respects: (i) relative abundance of individual proteins, which amounts in some cases to a complete absence in either sample, and (ii) varying molecular parameters for homologous proteins. It was thus possible to establish a first-generation reference map of rat serum proteins, which can be accessed through http://weber.u.washington.edu/ruedilab/aebersold++ +.html. We hope the present database will be a useful reference for the evaluation of changes in serum protein distribution in the course of pharmacological and toxicological studies. The recognition of species-specific proteins appears of special relevance in this respect.

Animals↗
PubMed1998

Proteins of rat serum: II. Influence of some biological parameters of the two-dimensional electrophoresis pattern.

This report complements the database already detailed for serum proteins of healthy adult male rats (P. Haynes et al., Electrophoresis 1998, 19, 1484-1492). The influence on the two-dimensional electrophoresis (2-DE) pattern of certain physiological conditions (sex, age) was studied as well as of changes in thyroid metabolism. We have extended the information about the major components of rat serum by identifying the proteins typical for the response to acute inflammation. Analyzing 27 spots, six proteins not found in control sera could be recognized; migration at overlapping or close positions with five already characterized proteins was observed for some. A compilation of all our rat data can be accessed through: http://weber.u.washington.edu/ruedilab/ aebersold.html.

Animals↗
PubMed1998

Lasting increase in serotonin 5-HT1A but not 5-HT4 receptor subtypes in the kindled rat dentate gyrus: dissociation from local presynaptic effects.

We examined the effect of kindling on serotonergic neurotransmission in the hippocampus by measuring serotonin (5-HT) release and uptake in hippocampal synaptosomes and 5-HT1A and 5-HT4 receptor subtypes during and at different times after electrical kindling of the dentate gyrus. Using quantitative receptor autoradiography, we found that binding of 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors was selectively increased by 20% on average (p < 0.05) in the dentate gyrus of the stimulated and contralateral hippocampus 2 days after stage 2 (stereotypes and occasional retraction of a forelimb) and by 100% on average (p < 0.05) 1 week after stage 5 (tonic-clonic seizures) compared with sham-stimulated rats. A 20% increase (p < 0.05) was observed 1 month after the last generalized seizure. No changes were found after a single afterdischarge. 5-HT4 receptors, which colocalize with 5-HT1A receptors on hippocampal neurons, were not modified in kindled tissue. [3H]5-HT uptake and its release as well as the 5-HT1B autoreceptor function did not differ from shams in hippocampal synaptosomes at stages 2 and 5. Systemic administration of 100 and 1,000 microg kg(-1) 8-OH-DPAT or 1,000 microg kg(-1) WAY-100,635, 30 min before each electrical stimulation, did not significantly alter kindling progression or the occurrence of stage 5 seizures in fully kindled rats. The changes in 5-HT1A receptor density in the dentate gyrus are part of the plastic modifications occurring during kindling and may contribute to modulating tissue hyperexcitability.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

On-line assessment of delivered dialysis dose.

BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent patient morbidity and mortality. The determination of effective ionic dialysance (D) is easy, non-invasive and inexpensive, and its use instead of effective urea clearance (K) in kinetically determining apparent" urea distribution volume (Vt) is likely to lead to a correct Kt/V, even though the Vt value may be incorrect. The aim of this study was to test the possibility of using the measurement of D to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four patients were dialyzed using a monitor equipped with specially designed "Diascan Module" (COT; Hospal) that measures effective D by means of a single conductivity probe. Vt was calculated according to the SPVV three BUN method urea kinetic model using D instead of K values. One month later, Kt/V was calculated as Dt/V, using actual D and T values and the predetermined Vt values updated for the current final body wt. Both the Dt/V and Kt/V determined according to the Smye and Daugirdas methods were compared with the Kt/V determined using the SPVV kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/- 0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17, mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once Vt has been determined, the evaluation of ionic dialysance in stable patients makes it possible to calculate the Kt/V accurately at each dialysis session without blood or dialysate sampling, and at no additional cost.

Blood Urea Nitrogen↗
PubMed1998

Morbidity and mortality on maintenance haemodialysis.

Despite the many technical advances in medical care and dialysis delivery, mortality and morbidity remain high in end-stage renal disease (ESRD) patients. A number of factors seem to contribute. Cardiovascular diseases are the leading cause of death: volume overload, anaemia, hypertension, arteriovenous fistula, uraemia-related myocardial cell injury all contribute to the development of ischaemic heart disease and congestive heart failure. The underlying disease is determinant for prognosis, with diabetics displaying an excess cardiovascular mortality. Elderly are also more likely to experience intercurrent medical conditions, vascular disease and diabetes, thus increasing the risk of death. Protein-energy malnutrition and wasting also contribute to the higher mortality in renal replacement therapy. Although nowadays high-risk patients are dialysed too, the rate of acceptance of ESRD patients still varies widely in different countries, possibly because of hidden selection criteria. The patients in the registries with a higher acceptance rate are more likely to be affected by co-morbid conditions and greater disease severity; the assessment of these co-morbid conditions is extremely important when comparing outcomes in different haemodialysis populations. Dialysis adequacy, obtained by means of longer duration of the treatment, is also of paramount importance; it allows minimizing the clinical effects of ultrafiltration and ensure that correct dry weight is reached. This means decreasing the incidence of intradialytic hypotensive episodes, but also improving blood pressure control, a strong predictor of survival. Family and social support, together with adequate medical care, greatly affect the quality of life of patients and can improve compliance to dialysis, diet and drugs and therefore survival.

Adult↗