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Biomedical subjects

M Arias

Publications and source records attributed to M Arias.

At least 109 records · Page 6Linked to original sources

Removal of xenoreactive antibodies by protein-A immunoadsorption: experience in 22 patients.

The presence of naturally occurring anti-Galalpha1-3Gal (antialphaGal) Ab in human serum is believed to be a major factor in the pathogenesis of hyperacute rejection of discordant organ xenografts such as the pig-to-human combination. Galalpha1-3Gal epitopes are expressed on pig tissues and the binding of anti-Galalpha1-3Gal leads to endothelial cell activation and complement-mediated hyperacute graft rejection. Several strategies have been suggested in donor animals or in the xenograft recipient to overcome the anti-alphaGal barrier. Protein-A immunoadsorption (PAIA) was developed for the in vivo removal of circulating Ab and it has been shown to be effective in cases where pathogenic auto or alloAb are present. The aim of our study was to analyze the effect of PAIA on total and xenoreactive serum anti-alphaGal immunoglobulin levels in a group of patients treated with this technique for different diseases. After three consecutive sessions of PAIA, total and xenoreactive IgG and IgM immunoglobulin levels were decreased by more than 50% of pre-treatment levels. So we conclude that PAIA is an effective method to significantly reduce circulating Ab, including xenogeneic IgM and IgG Ab. This mode of therapy might be considered as a tool to overcome hyperacute xenograft rejection. PAIA combined with other therapeutic approaches may well protect the xenograft.

Adolescent↗

Elevated serum concentrations of soluble CD14 in HIV- and HIV+ patients with tuberculosis in Africa: prolonged elevation during anti-tuberculosis treatment.

Data are limited regarding serum concentrations of soluble CD14 (sCD14), a marker of macrophage activation, in patients with active tuberculosis (TB) and during drug treatment. In this study, concentrations of sCD14 were measured in serum samples obtained from 105 African subjects who were categorized into one of four groups: persons with pulmonary TB alone (TB+HIV-, n = 30), pulmonary TB and HIV co-infection (TB+HIV+, n = 20), or HIV infection alone (TB-HIV+, n = 25), and healthy controls (TB-HIV-, n = 30). Mean total sCD14 was significantly increased in serum of patients with newly diagnosed pulmonary TB (mean = 6.6 g/ml, s.d. = 1.6 g/ml) compared with healthy controls (mean = 3.1 g/ml, s.d. = 0.6 g/ml; P < 0.0001), and this elevation comprised proportionate increases in the alpha (2.1-fold greater, P < 0.0001) and beta (2.0-fold greater, P < 0. 0001) forms of sCD14. Total sCD14 was also increased in serum of HIV-infected patients (mean = 4.1 g/ml, s.d. = 1.9 g/ml; P < 0.01), but the highest concentrations were observed in patients with pulmonary TB and HIV co-infection (mean = 8.7 g/ml, s.d. = 3.1 g/ml; P < 0.0001). Analysis of serum samples prospectively collected from TB+HIV-patients during the first 3 months of successful anti-TB treatment demonstrated steep reductions in mean concentrations of the acute-phase protein, C-reactive protein, and the soluble lymphocyte activation marker, sCD25. In contrast, levels of sCD14 increased during the first month of treatment and slowly declined thereafter. These data indicate that the serum concentration of sCD14 is not a sensitive index of response to anti-TB treatment and suggest that cellular activation resolves more slowly in the macrophage pool compared with the lymphocyte pool during anti-TB treatment.

Adult↗

Hemodiafiltration with online regeneration of the ultrafiltrate.

The concept of regeneration of dialysis fluids and of ultrafiltrate in particular has been recently revisited. Hemodiafiltration with online regeneration of the ultrafiltrate allows the concomitant infusion of sodium, calcium, and bicarbonate. Here, we studied the adsorptive characteristics of an integrated two-step sorbent system relative to different solutes present in the ultrafiltrate: sodium, calcium, phosphate, bicarbonate, uric acid, creatinine, and beta2-microglobulin. In vitro studies were performed in order to differentiate the relative roles for each sorbent (mineral-activated charcoal or hydrophobic resin) in adsorbing a given solute. Ex vivo studies were performed in order to evaluate the presence of cytokines (interleukin-1 beta and tumor necrosis factor-alpha), of cytokine (interleukin-1 beta and tumor necrosis factor-alpha)-inducing activities, and of the cytokine release in response to exogenous bacterial lipopolysaccharide by normal whole blood incubated with ultrafiltrate samples obtained at 15, 120, and 240 minutes after the start of treatment. The results of the present studies show the presence of immunomodulatory substances in the ultrafiltrate and the significant (P < 0.01) increase in the lipopolysaccharide-induced release of both interleukin-1 beta and tumor necrosis factor-alpha. The biological relevance of the ultrafiltrate and the possible relevance of the online, endogenous reinfusion are discussed.

Adsorption↗

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗

B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2.

BACKGROUND: Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF. METHODS: Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry. RESULTS: Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease. CONCLUSIONS: Our data indicate that B lymphopenia in CRF may be partially attributed to an increased susceptibility to cell death by apoptosis that is associated with a decreased expression of Bcl-2.

Adolescent↗

Hemodiafiltration with on-line endogenous reinfusion.

Paired filtration dialysis is a modified form of hemodiafiltration with a double-chamber hollow fiber. Convection is separated from diffusion, eliminating the potential risk of backfiltration (which can contain endotoxin or cytokine-inducing substances). The regeneration of high volumes of plasma ultrafiltrate obtained in the first filter allows a large plasma volume to be treated, and at the same time enables the return of many beneficial substances such as hormones, small peptides and many vitamins. Ultrafiltrate is regenerated with a charcoal-resin device and reinfused to the patient. Hemodiafiltration with on-line endogenous reinfusion is an easy and safe procedure. In addition, the method avoids risks associated with exogenous fluid infusion (endotoxin, pyrogens), allows exchange at no extra costs of large volumes of fluids and reduction in storage of fluid bags. Clinical advantages also include infusion of physiological fluid containing bicarbonate and calcium, good clinical tolerance and cardiovascular stability.

Adsorption↗

Survey of the furosine content in cheeses marketed in Spain.

The furosine content in 53 samples of different cheese types (fresh, ripened with molds, artisanal hard-pressed, industrial hard-pressed, and processed) marketed in Spain was analyzed. The lowest furosine values were observed in artisanal hard-pressed cheeses (4.8 to 10.2 mg per 100 g of protein) and ripened with molds cheeses (4.2 to 12.8 mg per 100 g of protein). Industrial hard-pressed cheeses showed furosine values between 3.5 and 43.8 mg per 100 g of protein. Differences between samples may be attributed to the heat-treatment intensity given to cheese milk and to cheesemaking conditions. The highest contents of furosine were observed in processed cheeses (20 to 366.6 mg per 100 g of protein). A wide range of furosine content was found in fresh cheeses (17.9 to 73.6 mg per 100 g of protein), which could be due to the different amounts of dried milk added during the manufacture of cheeses.

Animals↗

[Malignant prolactinoma with intra- and extracranial metastasis: clinico-radiologic study].

Malignant prolactinomas are very rare pituitary neoplasms which can be identified not from the hystopathologic nor neuroimaging aspects but only retrospectively from the presence of distant metastases. A 32-year-old male patient was diagnosed of a pituitary prolactinoma because of bitemporal hemianopsia on the basis of cranial MRI aspect and raised blood prolactin level. Visual signs improved under bromocriptine treatment but after surgical and X-ray therapies patient developed paralysis of V and XII left cranial nerves and suffered from medulocerebelous angle, vertebrae, spinal epidural space, lung, liver, suprarenal and femoral metastases. Patient died 3 years after the diagnosis time. Prolactin levels raised 2000 ng/ml. This is the first case of malignant prolactinoma described in the spanish literature and the more large one in number of metastatic localizations between the malignant prolactinomas from the literature. These kind of neoplasms can be partially ameliorated under X-ray and bromocriptine treatment but there is not, by the moment, a curative chemotherapy.

Adult↗

Differences in anti-CREG antibody formation between transplanted and nontransplanted renal patients.

BACKGROUND: The aim of this study was investigation of the HLA-I cross-reactive group (CREG)-specific antibodies (Abs) in sera from patients with a failed renal transplant and from nontransplanted patients. METHODS: A total of 5292 sera from 570 patients awaiting kidney transplantation were screened for the presence of HLA-I CREG-specific Abs. Patients who had never received a transplant (group A), and those with a previous transplant and Abs either not related (group B) or related to donor specificities (group C) were studied. A further division was made for Abs directed against specificities either included in (intra-CREG) or not included in patients' HLA-CREG (extra-CREG). RESULTS: Twelve of 24 (50%) Abs produced in response to mismatched donor HLA specificities after a failed graft were intra-CREG Abs, compared to 7 of 39 (18%) Abs that were not transplant-related. CONCLUSIONS: Renal grafts showed a stronger immunogenicity than other sources of allosensitization. Our data also suggest that CREG matching may not be useful for renal allocation.

Antibodies↗

Variants of the human NRAMP1 gene and altered human immunodeficiency virus infection susceptibility.

In a population-based case-control study, 182 human immunodeficiency virus (HIV)-positive persons and 135 healthy control subjects were enrolled from the metropolitan area of Medellin, Colombia. Four genotypes of the natural resistance-associated macrophage protein l (NRAMP1) gene (5' GT repeat, 274C/T, 469+14G/T, and 823C/T) were associated with altered risk of HIV infection (P=.013,.015,.020, and. 035, respectively). Three of these markers (5' [GT]n, 274C/T, 469+14G/T) are in strong linkage disequilibrium, and genotypes of these markers are associated with reduced risk of HIV infection with relative risks (RRs) of 0.35 (95% confidence interval [CI], 0.14-0.91), 0.31 (CI, 0.10-0.93), and 0.24 (CI, 0.08-0.72), respectively. Conversely, heterozygosity at the fourth independent marker (823C/T) was associated with increased risk of HIV infection (RR, 2.29; CI, 1.06-4.92). These findings suggest that NRAMP1 modifies risk of HIV infection.

Alleles↗