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Biomedical subjects

J M Miranda

Publications and source records attributed to J M Miranda.

At least 19 recordsLinked to original sources

Analysis of the electric field induced forces in erythrocyte membrane pores using a realistic cell model.

We calculate the induced electric stress forces on transient hydrophobic pores in the membrane of an erythrocyte exposed to an electric field. For this purpose, we use a finite element numerical technique and a realistic shape for the biconcave erythrocyte represented by a set of parametric equations in terms of Jacobi elliptic functions. The results clearly show that the electrical forces on the base and sidewalls of the pore favour the opening of the pore. A comparison of the force densities obtained for an unstretched flat membrane and for the realistic erythrocyte model shows that the thinning and curvature of the membrane cannot be neglected. We also show that the pore deformation depends strongly on the orientation of the pore with respect to the external field, and in particular is very small when the field is tangent to the membrane surface.

Biomechanical Phenomena↗

Tolerogenic response: allorecognition pathways.

The induction of immune tolerance in transplant recipients has been sought for many years but only a fundamental understanding of the immunological mechanisms underlying graft rejection will allow manipulation of the anti-graft immune response. In general, acute rejection is better understood and treated than chronic rejection, as they occur through partially different mechanisms. It is now generally accepted that recognition of same-species, non-self antigens (allorecognition) occurs through at least two different mechanisms, the direct and indirect pathways. In the direct pathway, donor MHC molecules on the surface of donor antigen-presenting cells (APCs) are recognised directly by the recipient's T cells. This mechanism is so immediate that it seems to be primarily involved in acute graft rejection. Since APCs of donor origin are depleted with time a second mechanism, the indirect pathway, takes over to cause chronic rejection, in which foreign MHC molecules are internalised, partially digested and presented as peptides to recipient T cells. Nonetheless, a number of studies are only fully understood when a third proposed allorecognition mechanism is taken into account. This is the semi-indirect pathway, as discussed in this short report.

Antigen-Presenting Cells↗

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Journal Article↗

Differential analysis of donor characteristics for pancreas and islet transplantation.

Suitable selection of donors is key to the success of human islet isolation and transplantation. Although several important donor-related factors have been identified previously, they needed to be confirmed in our setting. The aims of this study were: (1) to compare the characteristics of islet donors with those of pancreas donors (national transplant registry). (2) to compare the characteristics of islet donors resulting in a successful isolation in our facility with the characteristics of pancreas donors, and (3) to compare the characteristics of islet donors at this facility, whether or not isolation was successful, with donors elsewhere whose islets were transplanted and included in the Collaborative Islet Transplant Registry. The 35 islet isolations completed at our facility were analyzed for various characteristics. Significant differences were seen in donor age body mass index (BMI), and body weight between our islet donors and our pancreas donors (P < .001). These differences were maintained in the subgroup analysis corresponding to donors of successful isolations compared to pancreas donors (P < .01). Most successful isolations in our islet isolation facility were associated with donors of BMI >25. The percentage of successful isolation (>300,000 IEq) was higher among donors with a body weight >90 kg. We concluded that there was little overlap between the donor profiles for pancreas transplantation and for islet transplantation. More specific selection criteria relative to both BMI and body weight for islet donors may result in greater success of pancreas islet isolation and transplantation.

Adult↗

Effect of cooking on enrofloxacin residues in chicken tissue.

The aim of this study was to determine the effect of different cooking processes (microwaving, roasting, boiling, grilling and frying) on naturally incurred enrofloxacin residues in chicken muscle. Enrofloxacin and its metabolite, ciprofloxacin, were analysed using a validated LC-MS method with limits of detection (LOD) and quantification (LOQ), respectively, of 2 and 5 ng g-1 quinolones in muscle samples. The method was shown to be linear over the range 5-500 ng g-1. Mean intra-day relative standard deviation (RSD) at a concentration of 50 ng g-1 (n = 6) was 6%; inter-day RSD was 12%. A recovery study demonstrated that 65-101%, of the drug and metabolite could be recovered from the tissue. The RSD with naturally incurred roasted chicken breast was 9.18% at a concentration of 11 +/- 1.01 ng g-1 (n = 6). In water, enrofloxacin remained stable for 3 h when heated at 100 degrees C. It was concluded that residue data from raw tissue are valid for estimation of consumer exposure to this drug, as well as the ADI calculations because cooking procedures did not affect enrofloxacin residues, which remained stable during heating. However, there was an apparent decrease in quinolone concentration in tissue because some was lost by exudation into the liquid used for cooking. Conversely, for a cooking procedure with water loss, there was an apparent increase in residue concentration.

Animals↗

Pancreas islet transplantation in patients with type 1 diabetes mellitus after kidney transplantation.

Diabetic patients with end-stage renal disease have a high mortality rate. A combined kidney-pancreas transplant is associated with greater life expectancy. Pancreas islet transplantation is an alternative involving a lower degree of morbidity. We present two patients, of 41 and 37 years of age, with a long history of diabetes mellitus (C-peptide negative), both with a previous kidney transplant, who had been treated with 22 and 28 U of insulin/d, respectively. Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one patient required occasional doses of insulin, and the other patient more than 50% reduced dose. After the first implant neither patient had any episodes of unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no transplant-related complications.

Adult↗

Internal assessment of a novel islet isolation facility in Spain.

UNLABELLED: Islet transplantation is a promising therapy in the treatment of diabetes mellitus. Herein we present the result from the first series of islet isolations carried out in our new islet isolation facility. The aims of study were to analyze the influence of various donor characteristics on the success of islet isolation and compare these outcomes with other European and American groups. Data from 22 completed islet isolation were used to compare donor and isolation variables among successful (>300,000 IEQs) versus unsuccessful isolations. The successful isolation rate from our laboratory was 31.8%. We did not see any significant differences between successful and unsuccessful groups according to donor characteristics, although age was close to significance (38.57 +/- 10.29 versus 48.33 +/- 12.39; P = .08). Donor age (1.12 [1.23; 0.99]) and body mass index (0.065 [1.32; 3.08]) were associated with isolation success in a logistic regression model. We did not find differences among intraprocedure variables with the exception of IEQ prepurification (409,073 +/- 115,041 versus 263,776 +/- 128,988; P < .05). IEQpre and IEQpost were positively correlated (P < .05). In comparison with other groups, we observed differences in some cases related to islet yield prepurification (P < .05) but not postpurification. Purity from our islet preparations was the highest from all considered groups (P < .05). Recovery was similar in all groups. CONCLUSIONS: In our experience, donor characteristics have no influence on the success rate. The digestion step is a critical factor for success. Our results with respect to IE yield were close to that of experienced groups.

Adult↗

Evaluation of Chromocult enterococci agar for the isolation and selective enumeration of Enterococcus spp. in broilers.

AIMS: To investigate the productivity and specificity of a new chromogenic enterococci selective medium (Chromocult enterococci agar) recently developed by Merck. METHODS AND RESULTS: The study was carried out comparing Chromocult enterococci agar with MRS agar (Merck), a basal lactic acid bacteria medium in current use. A total of 216 faecal samples from poultry were collected and enterococci populations were counted. Likewise, 100 randomly selected strains were identified for each medium. The differences found between the two media were analysed and discussed. CONCLUSIONS: A good sensitivity of 98% was obtained for Chromocult agar and all false-positive isolates obtained were identified as Leuconostoc spp. However significant differences (P<0.01) were obtained between the enterococci species isolation rates identified from these two media, suggesting the poor growth of some species in Chromocult enterococci agar. Viable counts of Enterococcus spp. obtained with MRS agar were significantly higher than those obtained with Chromocult enterococci agar. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of chromogenic media for microbiological analysis is increasing. Independent studies are important to evaluate newly developed chromogenic media.

Agar↗

Transmembrane voltage induced on altered erythrocyte shapes exposed to RF fields.

In this article, the transmembrane voltage induced on erythrocyte, codocyte, ovalocyte and spherocyte cell models exposed to a linearly polarised electromagnetic plane wave of frequency 1800 MHz is calculated. For this purpose, a finite element (FE) numerical technique with adaptive meshing is used. The results show that the value of the induced voltage on the original erythrocyte shape is higher than the one observed on the rest of the altered cell geometries studied. The erythrocyte shape and the membrane electric permittivity are shown to play a fundamental role on the values of the induced transmembrane voltage.

Animals↗

Modelling the internal field distribution in human erythrocytes exposed to MW radiation.

This paper studies the internal electric field distribution in human erythrocytes exposed to MW radiation. For this purpose, an erythrocyte cell model is exposed to linearly polarized electromagnetic (EM) plane waves of frequency 900 MHz and the electric field within the cell is calculated by using a finite element (FE) technique with adaptive meshing. The results obtained show the dependence of the induced electric field distribution on the main modelling parameters, i.e., the electrical properties (permittivity and conductivity) of the membrane and cytoplasm and the orientation of the cell with respect to the applied field. It is found that for certain orientations, the field amplification within the membrane of the erythrocyte shape cell can be higher than the one observed in an equivalent simple spheroidal geometry cell, commonly used in bioelectromagnetism. The present work shows that a better insight of the interaction of electromagnetic fields with basic biological structures is obtained when the most possible realistic cell shape is used.

Cell Membrane↗

A study of the electric field distribution in erythrocyte and rod shape cells from direct RF exposure.

This paper shows the importance of using realistic cell shapes with the proper geometry and orientation to study the mechanisms of direct cellular effects from radiofrequency (RF) exposure. For this purpose, the electric field distribution within erythrocyte, rod and ellipsoidal cell models is calculated by using a finite element technique with adaptive meshing. The three cell models are exposed to linearly polarized electromagnetic plane waves of frequencies 900 and 2450 MHz. The results show that the amplification of the electric field within the membrane of the erythrocyte shape cell is more significant than that observed in other cell geometries. The results obtained show the dependence of the induced electric field distribution on frequency, electrical properties of membrane and cytoplasm and the orientation of the cell with respect to the applied field. The analysis of the transition of an erythrocyte shape to an ellipsoidal one shows that a uniformly shelled ellipsoid model is a rough approximation if a precise simulation of bioeffects in cells is desired.

Animals↗

Analysis of the influence of the cell geometry, orientation and cell proximity effects on the electric field distribution from direct RF exposure.

This paper shows the importance of using a cell model with the proper geometry, orientation and internal structure to study possible cellular effects from direct radiofrequency exposure. For this purpose, the electric field intensity is calculated, using the finite element numerical technique, in single- and multilayer spherical, cylindrical and ellipsoidal mammalian cell models exposed to linearly polarized electromagnetic plane waves of frequencies 900 and 2450 MHz. An extensive analysis is performed on the influence that the cell geometry and orientation with respect to the external field have in the value of the electric field induced in the membrane and cytoplasm. We also show the significant role that the cytoplasmic and extracellular bound water layers play in determining the electric field intensity for the cylindrical and ellipsoidal cell models. Finally, a study of the mutual interactions between cells shows that polarizing effects between cells significantly modify the values of field intensity within the cell.

Cell Membrane↗

Prolactin in human systemic lupus erythematosus.

In the last decade, evidence has accumulated to support the hypothesis that both mild and moderate elevations of serum prolactin (PRL) participate in the clinical expression and pathogenesis of systemic lupus erythematosus (SLE). Hyperprolactinemia (HPRL) has been found in 20-30% of patients with SLE. HPRL seems to be associated with clinical activity of SLE during pregnancy. Although the relationship between HPRL and active SLE in non-pregnant patients is controversial, recent clinical and experimental studies support the potential role of prolactin (PRL) as a promoter of clinical activity and severity of SLE. Mild elevations of serum PRL secondary to microadenoma could trigger the onset of SLE in a subset of patients. Elevated PRL and interleukin (IL)-6 have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE. There is exciting new evidence that HPRL in SLE may be explained by stimulation of pituitary PRL secretion by cytokines. In addition, defects in peptidergic modulators and dopamine metabolism have been described in patients with SLE. The interactions between PRL, cytoquines, autoantibodies and organ involvement suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in SLE will help us to understand and treat this important autoimmune disease.

Autoantibodies↗

Clinical significance of serum and urine prolactin levels in lupus glomerulonephritis.

UNLABELLED: Prolactin (PRL) has been involved in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia has been connected with systemic activity. However, the clinical significance of PRL has not been investigated in lupus glomerulonephritis (GN). METHODS: We studied SLE patients (ACR criteria) with biopsy-proven renal disease. Renal histology was classified according to World Health Organization (WHO) criteria. Renal function tests, albuminuria, complement levels (nephelometry), anti-DNA antibodies (C. luciliae) and serum and urine PRL concentrations (RIA) were determined at baseline and at 4-month intervals for one year. Renal activity was defined as mild, moderate or severe according to serum creatinine, creatinine clearance, albuminuria, red blood cells (RBC), and casts. RESULTS: There were 26 patients with mean age 28.5 y and mean disease duration 47.9 months. Twenty patients had diffuse proliferative glomerulonephritis (GN), four had focal GN and two had membranous GN with proliferative changes. Renal activity was mild in ten patients, moderate in ten and severe in six. Mean serum (24.7+/-5.3) and urine (0.90+/-0.36) PRL levels were higher in patients with severe renal activity (P < 0.05 compared with mild group). PRL levels decreased after treatment, but this trend was not uniform during the follow-up period. CONCLUSION: Hyperprolactinemia was prevalent in SLE patients and high levels of PRL in the serum and urine could be related to severe renal disease.

Adolescent↗

Bromocriptine in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled study.

The objective of this study was to investigate the efficacy and safety of bromocriptine (BRC) as an adjunct to conventional treatment in systemic lupus erythematosus (SLE). A prospective, double-blind, randomized, placebo-controlled study compared BRC at a fixed daily dosage of 2.5 mg with placebo. Patients were followed for 2-17 months (mean 12.5 months). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), numbers of flares were recorded, and serum prolactin (PRL) levels were obtained at intervals during the study. Patients were allowed to take prednisone and immunosuppressive drugs. Sixty-six patients with SLE entered the study. Thirty-six were treated with BRC, and 30 controls received placebo. Sixteen patients were removed from the study during the treatment period: five in each group left the study because of adverse effects, five became pregnant, and one patient who took placebo died with central nervous system lupus. Four patients in the BRC treatment group and three patients in the placebo group moved away or stopped coming for study visits for unknown reasons, and were lost to follow-up during the course. At entry, serum PRL was (mean+/-s.d.) 24.8 ng/ml+/-18.4 in the BRC treatment group. This value fell to 5.8+/-9.0 after 12 months of treatment. Corresponding PRL values in controls were 23.7+/-22.1 pretreatment and 20.3+/-14 after 12 months. PRL levels in BRC-treated subjects were significantly lower than levels in control subjects after 3, 6, 9, and 12 months of treatment. The SLEDAI score on the fifth protocol visit was decreased significantly in the BRC group vs controls: 0.9+/-1.4 vs 2.6+/-4.5 (P < 0.05). Although the absolute number of flares in each group was similar, the mean number of flares/patient/month was decreased significantly in the BRC group compared to the control group (0.08+/-0.1 vs 0.18+/-0.2, P = 0.03). Long term treatment with a low dose of BRC appears to be a safe and effective means of decreasing SLE flares in SLE patients.

Adult↗

Acute abdomen in systemic lupus erythematosus: the importance of early laparotomy.

BACKGROUND: Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a challenging diagnostic and therapeutic problem. Most patients are on steroid and/or immunosuppressive treatment and mortality is high. METHODS: We assessed the relationship between the causes of AA in SLE and the SLE disease activity index (SLEDAI). RESULTS: Of 51 patients with SLE and AA, 36 had active disease (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and 14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2 consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality was high in the active group (14 patients) compared with inactive SLE (2 cases). A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on the prognosis. CONCLUSIONS: In SLE patients with AA, a SLEDAI score below 5 is indicative of non-SLE-related AA. Elevated aCL were found in patients with intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low mortality, provided an appropriate surgical treatment is given. Early laparotomy influences positively the prognosis of SLE patients with AA.

Abdomen, Acute↗