Biomedical subjects

R Correa

Publications and source records attributed to R Correa.

At least 37 records · Page 2Linked to original sources

PubMed1999

Effect of a diet supplemented with thioproline on murine macrophage function in a model of premature ageing.

A previous study has shown that diet supplementation with thioproline (thiazolidine-4-carboxylic acid, TCA), an intracellular sulfhydril antioxidant and free radical scavenger, stimulates lymphocyte functions in old mice. In the present work, the effect of thioproline ingestion on the phagocytic functions of peritoneal macrophages, namely adherence, chemotaxis, phagocytosis and superoxide anion production was studied in adult female OF1-Swiss mice, that were fed thioproline (0.1% w/w) for five weeks, starting this ingestion at the age of 22 +/- 2 weeks. Mice were divided into a fast and a slow group based on their exploratory activity, which was assessed by their performance in a T-shaped maze. Slow mice showed a worse phagocytic activity with respect to fast animals. After thioproline treatment, a stimulation of all the functions studied as well as a neutralization of the superoxide radical were observed. The effect of this antioxidant was stronger in the slow than in the fast group. Thus, a diet supplemented with thioproline may enhance the immune functions, especially when they are depressed.

Aging↗

PubMed1999

Improvement of murine immune functions in vitro by thioproline.

Previous studies have shown that several immune functions were improved in mice after the ingestion of a thioproline (thiazolidine-4-carboxylic acid) enriched diet. In the present work, we have studied the in vitro effects of several concentrations of this thiol compound (0.1, 0.5, 1, 2.5 and 5 mM) on the most relevant functions of three pivotal immune cells, namely, macrophages, lymphocytes, and natural killer (NK) cells from BALB/c mice. The results show that thioproline stimulates the phagocytic process of macrophages, increasing the mobility directed to the inflammatory focus (chemotaxis) and the phagocytosis of inert particles. It increases the adherence and the chemotaxis capacities of lymphocytes, their proliferative activity and favours the natural cytotoxic activity that could improve the capacity to destroy malignant cells. Thioproline concentrations of 0.5 and 1 mM were the most effective regarding the different functions analysed. These results suggest that the improvement of immune functions, observed in previous work, after thioproline-enriched diet ingestion is due to a direct action of this thiol compound on immune cells.

Animals↗

PubMed1999

Effects in vitro of several antioxidants on the natural killer function of aging mice.

The aim of the present work is to study the change with aging in the effect in vitro of several antioxidants: thiazolidine-4-carboxylic acid or thioproline, N-acetylcysteine (NAC), ascorbic acid (AA), and alpha-tocopherol (vitamin E, VE) on the natural killer (NK) activity in mononuclear cells from axillary nodes, spleen, thymus and peritoneal leukocytes from BALB/c male mice. Young (8+/-2 weeks), adult (24+/-2 weeks). mature (48+/-2 weeks), and old (72+/-2 weeks) animals were studied. A nonradioactive cytotoxic assay with cells from the murine lymphoma YAC-1 as target cells and a relation effector cells/target cells of 10/1 were used. The concentrations of the different antioxidants were: 1 mM for thioproline and N-acetylcysteine and 5 microM for ascorbic acid and alpha-tocopherol, which induced a maximum effect in our previous dose-response experiments. The results show that, in general, the above antioxidants cause an enhancement of the NK activity at all ages studied, this stimulation being higher with thioproline and N-acetylcysteine than with ascorbic acid and alpha-tocopherol. The effects were similar for the three lymphoid organs and the peritoneum. This stimulation of the NK activity by antioxidants is an important favorable response, especially in old mice, in which age results in a decrease in NK function and, therefore, in a higher incidence of neoplasia.

Acetylcysteine↗

PubMed1999

ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia.

We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h x 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.

Animals↗

PubMed1998

Social influences: living arrangements of drug using women at risk for HIV infection.

The purpose of this study was to explore the associations among living arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322 drug users participating in the University of Miami CARES (Community AIDS Research and Evaluation Studies) HIV intervention program. Living arrangements may be associated with HIV prevention behaviors; however, these influences can be either protective or destructive and therefore merit further examination. Statistical analyses indicated differences in the living arrangements of women compared with men, and significant associations were noted among women's living arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The data from this study suggest that future HIV prevention research should investigate not only high-risk individuals, but persons with whom they interact often, especially those with whom they live or with whom they have sex. The next phase of HIV and drug interventions should be attentive to the incorporation of social context and social influences, paying particular attention to understudied populations such as high-risk women.

Adult↗

PubMed1997

Human schistosomiasis in Puerto Rico: reduced prevalence rate and absence of Biomphalaria glabrata.

A combined epidemiologic and malacologic survey of schistosomiasis in Puerto Rico was carried out in areas where previous surveys had reported the prevalence of the disease. This limited survey, with 495 persons examined, found a low prevalence (0.6%) of Schistosoma mansoni infections. The infections were restricted to three people more than 36 years of age. No infections were detected in children 16 years of age or less, and this cohort comprised 57.8% of the study group. Malacologic surveys of the four streams, 10 rivers, and eight lakes throughout the island revealed the absence of intermediate host Biomphalaria glabrata and the presence of Thiara granifera, a competitive species of B. glabrata and the predatory snail Marisa cornuarietis. We believe that the absence of B. glabrata is the primary reason for the sustained reduction in the prevalence of schistosomiasis in Puerto Rico.

Adult↗

PubMed1996

Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats.

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.

Animals↗

PubMed1995

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

Animals↗

PubMed1995

Ultrastructure of calcitonin gene-related peptide-immunoreactive, unmyelinated afferents to the cat carotid body: a case of volume transmission.

To relate the ultrastructure of unmyelinated afferents to the cat carotid body with the known electrophysiological properties of cat chemosensory C-fibers, we took advantage of the fact that the calcitonin gene-related peptide is exclusively present in a population of sparsely branched afferents to the carotid body. They have a morphology identical to the afferents originating from carotid sinus nerve unmyelinated axons. Immunoreactive axons were stained using pre-embedding protocols and horseradish peroxidase-labeled secondary antibody. Labeling was present only in unmyelinated axons and boutons distributed in the interstitial and parenchymal tissue. The varicosities had an average diameter of 0.7 micron, and contained both small, clear vesicles and larger dense-core vesicles. No labeled axons were ever seen to contact glomus cells, but could be observed as close as 0.2 micron to a glomus cell, always with an interposed glial process. With a very sensitive protocol, that used tungstate-stabilized tetramethylbenzidine as the chromogen, amorphous deposits of reaction product were often detected in the extracellular space around a labeled bouton. We interpret these findings as indicating that the reciprocal chemical transmission between the oxygen-sensitive glomus cells and the unmyelinated afferents takes place through non-synaptic transmission, via the rather large extracellular space of the carotid body. In addition, the larger distances between glomus cells and unmyelinated afferents could explain the lowered sensitivity and sluggishness of chemosensory C-fibers, compared to the A-fibers.

Afferent Pathways↗

PubMed1995

Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs.

We studied the differential hemodynamic effects of N omega-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, in normal and endotoxemic dogs and examined its activity across the venous, pulmonary, and systemic circulations. Survival was used to determine therapeutic efficacy. In both normal and endotoxemic animals, L-NMMA similarly increased systemic (P = 0.01) and pulmonary (P = 0.047) vascular resistance, marginally increased mean arterial pressure (P = 0.07), and decreased oxygen delivery (P = 0.01) compared with normal saline. In contrast, the effect of L-NMMA on mean pulmonary arterial pressure, central venous pressure, and pulmonary capillary wedge pressure was different in endotoxemic than in normal animals (P < 0.05), but this differential effect occurred > 6 h after endotoxin challenge. L-NMMA (1-10 mg.kg-1.h-1) did not significantly increase survival rates or times in endotoxemic animals, but the highest dose decreased survival times (P < 0.05). Thus the effect of L-NMMA was similar on the systemic arterial circulation in endotoxemic dogs compared with normal dogs but was increased in the venous and pulmonary vascular beds after endotoxin, suggesting that the induction of NO production was greater in low-resistance vessels. We were unable to show that nonselective inhibition of NO production was beneficial in endotoxemic dogs.

Animals↗

PubMed1994

Hemoglobins from Plasmodium-infected rat erythrocytes: functional and molecular characteristics.

Aiming to evaluate the mechanisms responsible for altered O2-transporting properties in blood of Plasmodium-infected animals, stripped (cofactor-free) hemoglobin (Hb) solutions were prepared from infected erythrocytes (IE) and noninfected erythrocytes (NIE) of rats inoculated with Plasmodium berghei bergei for functional and structural characterization. At normal intraerythrocytic pH (+/- 7.2), Hb from IE showed a higher affinity, a larger Bohr effect, and lower sensitivities to 2,3-diphosphoglycerate (DPG) and to temperature than did NIE Hb. Moreover, as judged from electrophoresis, isoelectric focusing, and gel filtration experiments, Hb from IE show changes in charge and molecular assembly. The results indicate that the higher O2 affinity and greater Bohr factors observed in IE compared with those for NIE are attributable to chemical modification of the Hb that increases its intrinsic O2 affinity and decreases its sensitivity to DPG as well as to changes in the intracellular physicochemical milieu, including reduced DPG levels.

Animals↗

PubMed1994

Oxygen transport properties in malaria-infected rodents--a comparison between infected and noninfected erythrocytes.

This study was performed to investigate oxygen transport properties in whole blood (WB) of malaria-infected rats as well as in infected erythrocytes (IE) and noninfected erythrocytes (NIE) separated by density centrifugation. One week after inoculation with Plasmodium berghei, mean parasitemia was 26.5% and high correlations were found between parasitemia and hemoglobin concentration ([Hb]; r = -.902), mean cellular Hb concentration (MCHC; r = -.712), MetHb (r = .923), and base excess (r = -.922). Compared with control animals (C), the oxygen affinity was lower in WB under standard (pH 7.40) and simulated "in vivo" (pH 7.00) conditions (difference in P50, 5.7 and 5.1 mm Hg, respectively; 2P < .01, 2P < .05). In IE Hb and 2,3-biphosphoglycerate (2,3-BPG) concentrations were decreased (MCHC: IE 14.6 +/- 1.0, NIE 33.1 +/- 1.7 g/100 mL; [2,3-BPG]: IE 2.0 +/- 0.6, NIE 7.6 +/- 1.8 mmol/L), whereas [MetHb] and [ATP] were increased ([MetHb]: IE 19.0 +/- 3.7, NIE 0.7% +/- 0.8%; [ATP]: IE 33.5 +/- 2.4, NIE 6.2 +/- 1.0 mumol/g Hb). At pH 7.40, half-saturation oxygen tension (P50) was reduced in IE (29.6 +/- 2.6, NIE 39.2 +/- 5.4 mm Hg, 2P < .001), which correlates with lower [2,3-BPG], increased MetHb content, and higher intrinsic Hb-O2 affinity. However, at pH 7.00, the oxygen affinity was lower in IE when compared with NIE, which was most likely due to high [ATP] in IE. The resulting Bohr coefficients (BC) calculated for CO2 and lactic acid were extremely high in IE and low in NIE (at 50% O2-saturation BCCO2: IE -1.04 +/- 0.06, NIE -0.26 +/- 0.10, 2P < .001; BCLac: IE -0.82 +/- 0.16, NIE -0.47 +/- 0.07, 2P < .001), which was caused by different [2,3-BPG] and [ATP] as well as probably by structural changes of the Hb molecule. The O2 capacity was 14.1 mL per 100 mL erythrocytes in IE compared with 44.4 mL/100 mL in NIE. On the basis of the calculated arterio-venous O2 difference under "in vivo" conditions, the infected red blood cell fraction transports 30% of the O2 amount delivered to the tissues by the noninfected cells (IE 8.0, NIE 26.9 mL/100 mL red blood cells). We conclude that the O2 transport in malaria infected blood is not only affected by the degree of anemia but also by the percentage of infected erythrocytes.

Adenosine Triphosphate↗

PubMed1994

Myocardial energy metabolism and morphology in a canine model of sepsis.

The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.

Adenosine Triphosphate↗

PubMed1994

Basic fibroblast growth factor enhances myocardial collateral flow in a canine model.

Basic fibroblast growth factor (FGF) is a multifunctional peptide that may play an integral role in angiogenesis associated with coronary collateral formation and myocardial infarct healing. We sought to determine the effects of exogenously administered basic FGF on collateral blood flow to ischemic myocardium. Ameroid constrictors were used to cause gradual occlusion of the left circumflex coronary artery in dogs. Basic FGF (110 micrograms, n = 9) or saline (n = 12) was given as a daily bolus injection directly into the collateral-dependent zone, beginning 10 days after placement of the Ameroid and continuing for 28 days. Collateral flow was assessed weekly as the ratio of collateral to normal zone (CZ/NZ) blood flow during maximal pharmacologically induced coronary vasodilation. The CZ/NZ increased in both treated and control dogs as a function of time; however, transmural collateral flow in basic FGF-treated dogs significantly exceeded that of control dogs by the second week of treatment. Final CZ/NZ blood flow ratios were 0.49 +/- 0.05 and 0.35 +/- 0.02 in the treated and control groups, respectively (means +/- SE, P = 0.0002). Treatment with basic FGF was also associated with significant increases in the numerical density of distribution vessels and endothelial cell DNA synthesis within the CZ. We also found that basic FGF had acute effects as a coronary vasodilator. Thus exogenous administration of basic FGF enhances maximal collateral blood flow in dogs with myocardial ischemia secondary to single-vessel coronary occlusion, an effect that is likely mediated through the direct angiogenic effects of the peptide, although its acute vasodilatory effects may also play a role.

Animals↗

PubMed1994

In vitro culture of cardiac mast cells from mice experimentally infected with Trypanosoma cruzi.

In this study we describe a mast cell population obtained by in vitro culture of hearts of Trypanosoma-cruzi-infected mice. Heart tissue was placed in culture and observed daily for the efflux of cells. Mast cells appeared in the medium during the 1st week of culture in the area immediately surrounding the tissues and increased in numbers over time. The cells were identified as mast cells by electron microscopy and by positive staining of granules with Giemsa, toluidine blue, and berberine sulfate techniques. Histopathological analysis of the cultured heart fragments from infected mice showed numerous mast cells, located mostly in areas where the histologic structure was abnormal and surrounded by fibrous connective tissue. This is the first report on in situ proliferation and migration of mast cells form inflamed heart tissues. In situ grown mast cells might be useful in developing in vitro models to study the role of these cells in T. cruzi-induced and other myocardiopathies.

Animals↗

PubMed1994

[Gallbladder polyps. 2d Consensus Workshop of the Chilean Hepatology Association].

During a workshop, hepatologists analyzed and gave recommendations about gallbladder polyps. They arrived to the following agreements: gallbladder polyps of less than 10 mm should be followed with ultrasonography at 3, 6 and 12 months if there is no enlargement. If there is enlargement, a cholecystectomy should be performed. Polyps larger than 10 mm should be subjected to cholecystectomy.

Female↗

PubMed1994

Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease.

Animals↗

PubMed1993

Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain.

Three members of a family who died with renal amyloidosis were found to share a single nucleotide substitution in the fibrinogen alpha-chain gene. The predicted arginine to leucine mutation (Arg554Leu) was proven by amino acid sequence analysis of amyloid fibril protein isolated from postmortem kidney of an affected individual. Direct genomic DNA sequencing and restriction fragment length polymorphism analysis demonstrated that all three affected individuals had the guanine to thymine 4993 transversion. This is the first demonstration of hereditary amyloidosis associated with a variant fibrinogen alpha-chain. Variants of circulating fibrinogen may be the cause of a number of systemic amyloidoses with primarily renal involvement.

Adult↗