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Biomedical subjects

A Campa

Publications and source records attributed to A Campa.

At least 37 records · Page 2Linked to original sources

Oxidative metabolism and release of myeloperoxidase from polymorphonuclear leukocytes obtained from blood sedimentation in a Ficoll-Hypaque gradient.

Polymorphonuclear neutrophils (PMN) have an important role in the host defence response to infection. These cells produce large amounts of reactive oxygen species (O(2).(-), H(2)O(2) and ONOO(-)) with microbicidal activity. PMN are commonly isolated from peripheral blood by sedimentation through a gradient of density (Ficoll-Hypaque gradient and dextran), yielding a highly homogeneous cellular population. However, some cellular activation due to membrane perturbation is also expected. We studied how the production of reactive oxygen species and release of myeloperoxidase (MPO) from blood PMN are affected by the use of the Ficoll-Hypaque density gradient. PMN isolated by spontaneous sedimentation and total blood were used for comparisons. Lucigenin- and luminol-enhanced chemiluminescence was used to estimate the production of reactive oxygen from intact cells and shown to be higher for cells isolated by density gradient both in the absence and presence of added stimuli. The release of MPO, estimated by the chemiluminescence of the luminol/H(2)O(2) reaction in the supernatant of PMN incubated in the absence and presence of stimuli and absence and presence of cytochalasin B, was also higher for PMN isolated by a density gradient. In conclusion, it was shown that the PMN isolation procedure affects reactive oxygen species production and MPO release and in some cases may cause a misinterpretation of results.

Acridines↗

Quality of life measures in the Miami HIV-1 infected drug abusers cohort: relationship to gender and disease status.

PURPOSE: This study examined activity, daily living, health, support, and outlook in HIV+ drug users. METHODS: Using the physician-administered Spitzer Index, the study assessed 75 HIV-1 seropositive men (n = 51) and women (n = 24) enrolled in the Miami HIV-1 Infected Drug Abusers Study (MIDAS). RESULTS: Total composite scores were significantly lower in the HIV-1 infected women than the men (p = .03). Significant gender differences were observed in activity assessment, independent of disease status, with women six times as likely to have lower activity scores (p = .0038). Most women (45%) in this category were homeless or marginally housed, compared to 11 percent of the men. Additionally, women with low activity scores had less social support than women with high activity scores. Cocaine use was significantly related to reports of normal activity, and varied across genders; more men used cocaine than women (p = .03). Compared to non-AIDS participants, AIDS patients were more likely to have lower scores in health (p = .009) and poorer outlook (p = .03). IMPLICATIONS: These findings reveal specific deficits in areas of psychosocial capacity, particularly in HIV-1 infected women who abuse drugs, that may need to be strengthened in order to enhance function and adherence to treatment, as well as well-being.

Activities of Daily Living↗

Lipid emulsion reduces subacute toxicity of amphotericin B: a histopathological study.

In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride-rich emulsion (AB-emulsion). The present paper compares the severity of the histopathological alterations as determined by morphometry produced in the target tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the conventional formulation AB-deoxycholate (DOC) following subacute AB treatment. No morphological alterations were seen in the spleen and heart following both AB-DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and lungs are basically the same for both formulations, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compared to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration. These three treatment regimens consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive days. Thus, these regimens consisted of total doses varying from 8-12 mg/kg of body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition, acute interstitial inflammation was observed in the lungs prior to interstitial and alveolar edema. The intensity of the histopathological damage increase with the dose and with the reduction in the time interval between AB administrations. Abnormal serum biochemical parameters were observed for serum urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decreased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effects induced by in vitro and in vivo tests with AB-emulsion treatment.

Amphotericin B↗

Selenium and interleukins in persons infected with human immunodeficiency virus type 1.

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.

Acquired Immunodeficiency Syndrome↗

Zinc status in human immunodeficiency virus infection.

There is substantial evidence to support an important role for zinc in immune processes. Adequate zinc status is essential for T-cell division, maturation and differentiation; lymphocyte response to mitogens; programmed cell death of lymphoid and myeloid origins; gene transcription; and biomembrane function. Lymphocytes are one of the types of cells activated by zinc. Zinc is the structural component of a wide variety of proteins, neuropeptides, hormone receptors and polynucleotides. Among the best known zinc-dependent hormones/enzymes are Cu, Zn superoxide dismutase, an enzyme component of the antioxidant defense system, and thymulin, which is essential for the formation of T-lymphocytes. In animals and humans, zinc deficiency results in rapid and marked atrophy of the thymus, impaired cell-mediated cutaneous sensitivity and lymphopenia. Primary and secondary antibody responses are reduced in zinc deficiency, particularly for those antigens that require T-cell help, such as those in heterologous red blood cells. In addition, antibody response and the generation of splenic cytotoxic T cells after immunization are reduced. Zinc also inhibits the production of tumor necrosis factor, which is implicated in the pathophysiology of cachexia and wasting in acquired immune deficiency syndrome.

Disease Susceptibility↗

Canonical solution of a system of long-range interacting rotators on a lattice

The canonical partition function of a system of rotators (classical X-Y spins) on a lattice, coupled by terms decaying as the inverse of their distance to the power alpha, is analytically computed. It is also shown how to compute a rescaling function that allows us to reduce the model, for any d-dimensional lattice and for any alpha<d, to the mean-field (alpha=0) model.

Journal Article↗

Pathogenesis I: interactions of host cells and fungi.

The interactions of host cells and fungi during infection represent a complex interplay. Although T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance to Paracoccidioides brasiliensis, studies have demonstrated that polymorphonuclear neutrophils play a critical role in providing an early resistance to this organism. One study has shown that the invasiveness of Candida albicans requires adherence, particularly to endothelial cells, which in turn are stimulated to express various cell-markers and pro-inflammatory cytokines as part of a proactive resistance to invasion. Somewhat in contrast to infection with C. albicans, it has been shown that the capsular glucuronoxylomannan of Cryptococcus neoformans causes the shedding of host-cell adherence molecules (L-selectins) needed for the migration of host-inflammatory cells to sites of infection and likely explains, in part, the reduced host inflammatory response to this organism. Resistance to aspergillosis is often associated with the immune status of the host. In one set of studies, it has been demonstrated that lymphocytes have little direct effect on the organism, but that antigen-presenting dendritic cells stimulate the production of Th1 cytokines, suggesting a positive role for the dendritic cell in host-response. Similarly, another study has shown that among the regulatory cytokine networks that Th2-associated cytokines (e.g., interleukin-10) likely play a detrimental role in the resistance of the host to Aspergillus fumigatus.

Animals↗

Mortality risk in selenium-deficient HIV-positive children.

OBJECTIVE: To determine the independent contribution of specific nutritional factors on disease progression and survival in HIV-1-infected children. POPULATION: HIV-infected children (N = 24), who were perinatally exposed to the virus and symptomatic, were recruited between October and December of 1990 from the Jackson Memorial Pediatric Immunology Clinic, Miami, Florida, and observed for 5 years. METHODS: Immune status was measured by CD4 cell count; nutritional status was determined using serum albumin and plasma trace elements including iron, zinc, and selenium. Cox proportional hazards regression models were used to evaluate the relationship of these parameters to survival. Use of antiretroviral treatment was considered in the statistical model, and age at death was considered a parameter of disease progression. RESULTS: Over the course of the study, 12 children died of HIV-related causes. The final Cox multivariate analysis indicated that, of the variables evaluated, only CD4 cell count below 200 (risk ratio [RR] = 7.05; 95% confidence interval [CI], 1.87-26.5); p = .004], and low levels of plasma selenium (RR = 5.96; 95% CI, 1.32-26.81; p = .02) were significantly and independently related to mortality. Among the children who died, those with low selenium levels (< or =85 microg/L), died at a younger age, suggesting more rapid disease progression. CONCLUSIONS: In pediatric HIV-infection, low plasma level of selenium is an independent predictor of mortality, and appears to be associated with faster disease progression.

Child↗

Pharmacological parameters of intravenously administered amphotericin B in rats: comparison of the conventional formulation with amphotericin B associated with a triglyceride-rich emulsion.

The LD50 determined in rats for the potent antifungal amphotericin B (AB) increased from 4.2 to 12.0 when the conventional AB-deoxycholate (DOC) was compared with AB associated with a triglyceride-rich emulsion (AB-emulsion). The reduction in amphotericin B toxicity is not due to a modification in plasma clearance, as both formulations seem to be removed from plasma at the same rate. Major differences in amphotericin B tissue distribution were not seen for kidney and liver but were seen for the lung. After 24 h administration of a single amphotericin B dose (2.0 mg/kg body weight) 23.78 +/- 11.71 mg/kg tissue was recovered from the lung of animals treated with AB-DOC whereas for AB-emulsion only 5.19 +/- 2.50 mg/kg tissue was recovered. The higher lethality of AB-DOC may be related to the higher concentration of amphotericin B in the lung. The therapeutic efficacy of AB-emulsion was similar to that of AB-DOC as attested by survival curves obtained after treatment of mice infected by Candida albicans. This is highly relevant, as the same is not necessarily found for other less toxic proposed vehicles. The equivalent efficacy and the increment in the LD50 will result in an important improvement in the therapeutic activity of amphotericin B. Furthermore, some data related to storage and stability indicate the clinical utility of this type of drug delivery.

Amphotericin B↗

HIV-1 infection in women is associated with severe nutritional deficiencies.

Nutritional deficiencies may contribute to immune dysregulation, and have been shown to be sensitive markers of HIV-1 disease progression. Only limited information exists, however, regarding the nutritional profile of HIV-1-seropositive drug abusers. Immune and nutritional measurements were obtained in a subsample of 125 subjects from a larger cohort of drug users being followed for HIV-1 infection and cofactors of disease progression. Nutritional deficiencies, particularly vitamins A, E, and zinc, were widespread with up to 86% of the drug users exhibiting at least one nutritional alteration. Although immune parameters (CD4 count, CD8 count, beta2-microglobulin) were similar in the HIV-1-infected men and women, women had significantly poorer overall nutritional status, as measured by plasma proteins, which are considered to be sensitive markers of malnutrition. A comparison of individuals with advanced disease (CD4 count <200/mm3) revealed significantly lower levels of plasma prealbumin (p < .01), selenium, (p < .05), and greater deficiency of vitamins A (p < .01) and E (p < .05) in women than in men. The greater severity of nutritional deficiencies noted in HIV-1-infected women may be an important determinant of disease progression and survival.

Adult↗

The effect in vitro of high-density lipoprotein from healthy and infected humans on the oxidative metabolism of polymorphonuclear leukocytes.

We studied the effects in vitro of high-density lipoprotein from healthy (N-HDL) and from infected humans (AP-HDL) on the oxidative metabolism of human polymorphonuclear leukocytes (PMN). Products of the H2O2-MPO-halide system were monitored by luminol-enhanced chemiluminescence and superoxide anion formation was monitored by lucigenin-enhanced chemiluminescence during stimulation of human PMN with phorbol myristate acetate (PMA) or an opsonized stimulus (OS). The results showed that N-HDL and AP-HDL affect the oxidative metabolism of PMN in different ways. The possible role of this effect is discussed.

Acridines↗

Effect of amphotericin B associated with a lipid emulsion on the oxidative burst of human polymorphonuclear leukocytes.

1. Despite its toxicity, amphotericin B (AB) continues to be the drug of choice for the treatment of systemic fungal infection. The drug acts on several cell types, including polymorphonuclear leukocytes (PMN), where it inhibits the oxidative burst of cells submitted to several stimuli. 2. It was previously shown that the association of AB with a triglyceride-rich emulsion that physiologically mimics chylomicrons reduces toxicity. 3. We found that the association of AB with a triglyceride-rich emulsion reduces the loss of PMN viability produced by the drug. 4. The inhibition of the PMN oxidative burst triggered by phorbol 12-myristate 13-acetate (PMA) and opsonized zymosan (OZ) also was decreased by the association of the drug with this lipid emulsion. 5. Delivery of AB in a lipid emulsion may be of advantage in the treatment of immunosuppressed patients.

Amphotericin B↗

A semi-empirical approach to the evaluation of the relative biological effectiveness of therapeutic proton beams: the methodological framework.

We address the problem of the evaluation of the relative biological effectiveness (RBE) of therapeutic proton beams for cell inactivation. We consider a general approach to the evaluation of the lethal effect of protons which is applicable to different situations, including those in which an extended Bragg peak is obtained via a modulated beam. Our approach combines two kinds of information: (1) the experimental results available in the literature for the response of Chinese hamster V79 cells to monoenergetic beams and (2) the energy spectrum of the beam in the target volume, computed through a Monte Carlo algorithm. We have applied this method to a simple Bragg peak produced by a broad-field proton beam of about 70 MeV initial energy, such as those that, after attenuation, are typically used for treatment of ocular tumors. We have found that the RBE increases with depth, even beyond the Bragg peak, up to a value close to 2, when evaluated at the same surviving fraction as that resulting after exposure to 2 Gy of X rays.

Animals↗

Esterase coupled with the H2O2/horseradish peroxidase system triggers chemiluminescence from 2-methyl-1-propenylbenzoate: a potential analytical tool for esterase analysis.

The hydrolysis of 2-methyl-1-propenylbenzoate catalyzed by esterase produces 2-methyl-1-propenol, which can be subsequently oxidized by the H2O2/horseradish peroxidase (HRP) system to yield electronically excited triplet acetone. The level of luminescence elicited by this species is proportional to total esterase used, making it possible to determine as little as 2 pmol of esterase. Yet, its intensity can be enhanced several orders of magnitude by fluorescent acceptors like sodium 9,10-dibromoanthracene-2-sulfonate. The system works as a chemiluminescent reaction triggered by esterase and can be used to elaborate analytical assays to determine its activity. This chemiluminescence is also promoted by HRP conjugates instead of free HRP and, hence, this simple reaction system can also be used to develop sensitive chemiluminescent immunoassays based upon peroxidase activity.

Aldehydes↗

Neutrophil oxidative metabolism and killing of P. brasiliensis after air pouch infection of susceptible and resistant mice.

The oxidative burst of polymorphonuclear neutrophils (PMN) and their ability to inhibit Paracoccidioides brasiliensis growth was studied in susceptible (B10.A) and resistant (A/J) mice. The cells were obtained after subcutaneous inoculation in air pouches, yielding highly pure PMN preparations; the number of cells was similar for both strains at 24 h and five times higher in the resistant strain at 15 days. The oxidative metabolism of these PMN was evaluated by the luminol and lucigen-enhanced chemiluminescence upon stimulation with PMA or killed P. brasiliensis (Pb). At 24 h of infection PMN from both strains showed similar responses. However, at 15 days a great enhancement of the Pb-stimulated luminol-enhanced chemiluminescence was observed only in PMN from resistant mice. Such increase was markedly inhibited by the addition of catalase. Independent of the mouse strain or time of infection of lucigen-enhanced chemiluminescence showed the same intensity. The lucigen-enhanced chemiluminescence of PMN without stimuli from resistant mice did not change with the time of infection, however, after 15 days of infection a significantly lower chemiluminescence was detected with PMN from susceptible mice. At 15 days of infection the PMN from B10.A were unable to kill P. brasiliensis yeast cells in vitro. Because the lucigenin- and luminol-enhanced chemiluminescence detects, respectively, the O2- production and the myeloperoxidase/hydrogen peroxide halide system, the present data show parallels between deficiency in the production of oxygen-reactive species by PMN and lower fungicidal activity.

Acridines↗

Plant hormone ethylene is a Norrish type II product from enzymically generated triplet 1-butanal.

The peroxidase-catalyzed aerobic oxidation of a linear aldehyde, leading to the next lower homologue in the triplet state, is accompanied by Norrish type II product ethylene when the substrate is pentanal. This system appears to provide an example of "photobiochemistry without light" because ethylene is a plant hormone and is formed in lipid peroxidation when the recurrent oxidation of linear aldehydes occurs.

Journal Article↗