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Biomedical subjects

L C Souza

Publications and source records attributed to L C Souza.

At least 19 recordsLinked to original sources
PubMed2001

Ventricular endocardial right bifocal stimulation in the treatment of severe dilated cardiomyopathy heart failure with wide QRS.

The QRS widening by ventricular conventional pacing impairs the systolic and diastolic functions and increases mitral regurgitation. The aim of this study was to compare conventional pacing to an alternative stimulation mode with a narrower QRS using two leads in the RV. Thirty-nine (25 men, 14 women; mean age 60.1 +/- 15.1 years) dilated cardiomyopathy patients (Chagas' disease [n = 17], coronariopathy [n = 9], AV ablation for tachycardiomyopathy [n = 3], and other [n = 10]) with cardiac failure (NYHA 3.1 +/- 0.8), pacemaker indication, and chronic AV block (22 AF) had endocardial pacemaker implantations (27 Biotronik, 12 Guidant). Two RV leads (one septal, one conventional [RV apex] were connected, respectively, to the atrial and ventricular pacemaker plugs. After clinical stabilization they were studied under three stimulation modes in the same session: AAI (septal), VVI (conventional), and ventricular endocardial right bifocal stimulation (VERBS) (DDT/DVI/DDD = AV interval = 15/10 ms). In comparison to conventional pacing, VERBS increased ejection fraction (0.124), cardiac output (19.5%), and peak filling rate (31.0%), and decreased QRS duration (24.7%), left atrium area (11.9%), mitral regurgitation area (32.3%), the diastolic transmitral flow (E/A relation) (19.3%), and the propagation flow time (18.0%) from the mitral valve to the left ventricular apex (tE_col), (P < 0.05). The quality-of-life showed an impressive score reduction of 50.4%. The septal stimulation alone showed a less expressive benefit. In severe dilated cardiomyopathy with classic pacemaker indication, VERBS showed significantly better performance than the septal or the conventional stimulation alone. There was a good systolic and a remarkable diastolic improvement causing an important reduction in the quality-of-life score.

Adult↗
PubMed2000

Inhibition of vascular NADH/NADPH oxidase activity by thiol reagents: lack of correlation with cellular glutathione redox status.

Vascular NAD(P)H oxidase activity contributes to oxidative stress. Thiol oxidants inhibit leukocyte NADPH oxidase. To assess the role of reactive thiols on vascular oxidase, rabbit iliac/carotid artery homogenates were incubated with distinct thiol reagents. NAD(P)H-driven enzyme activity, assessed by lucigenin (5 or 250 microM) luminescence, was nearly completely (> 97%) inhibited by the oxidant diamide (1mM) or the alkylator p-chloromercuryphenylsulfonate (pCMPS, 0.5mM). Analogous inhibition was also shown with EPR spectroscopy using DMPO as a spin trap. The oxidant dithionitrobenzoic acid (0.5mM) inhibited NADPH-driven signals by 92% but had no effect on NADH-driven signals. In contrast, the vicinal dithiol ligand phenylarsine oxide (PAO, 1 microM) induced minor nonsignificant inhibition of NADPH-driven activity, but significant stimulation of NADH-triggered signals. The alkylator N-ethyl maleimide (NEM, 0.5mM) or glutathione disulfide (GSSG, 3mM) had no effect with each substrate. Coincubation of N-acetylcysteine (NAC, 3mM) with diamide or pCMPS reversed their inhibitory effects by 30-60%, whereas NAC alone inhibited the oxidase by 52%. Incubation of intact arterial rings with the above reagents disclosed similar results, except that PAO became inhibitor and NAC stimulator of NADH-driven signals. Notably, the cell-impermeant reagent pCMPS was also inhibitory in whole rings, suggesting that reactive thiol(s) affecting oxidase activity are highly accessible. Since lack of oxidase inhibition by NEM or GSSG occurred despite significant cellular glutathione depletion, change in intracellular redox status is not sufficient to account for oxidase inhibition. Moreover, the observed differences between NADPH and NADH-driven oxidase activity point to complex or multiple enzyme forms.

Acridines↗
PubMed2000

Oxidative stress as a signaling mechanism of the vascular response to injury: the redox hypothesis of restenosis.

The prominent role of redox processes in tissue injury and in vascular cell signaling suggest their involvement in the repair reaction to vessel injury, which is a key determinant of restenosis post-angioplasty. Experimental studies showed a protective effect of superoxide dismutase or antioxidants on vasospasm, neointimal thickening or remodeling after balloon injury. It was also shown that oxidized thiols induce chelatable metal-dependent amplification of the vascular repair reaction. Ongoing or completed clinical trials show a promising effect of the antioxidant probucol against restenosis. However, few studies addressed the molecular physiological mechanisms underlying the redox hypothesis of restenosis. We recently showed evidence for marked oxidative stress early after balloon injury, with superoxide production mediated primarily by non-endothelial NAD(P)H oxidase-type flavoenzyme(s). This effect was closely related to the degree of injury. There is evidence supporting a role for such early redox processes in apoptotic cell loss and NF-kappa B activation. We present new data on the time course of oxidative stress after balloon injury of intact rabbit iliac arteries. Our data show that despite substantial neointimal growth and lumen narrowing, superoxide production and glutathione levels are unaltered at day 14 and 28 after balloon injury. At day 7 after injury, the peak neointimal proliferation in this model, there was significant decrease of vascular superoxide dismutase activity, without clear evidence of spontaneous superoxide production. Thus, oxidative stress after injury is likely to be an early transient event, which parallels the inflammatory and proliferative phases of the vascular response. We propose that such early redox processes act as dose-dependent signal transducers of gene programs that affect the final repair.

Angioplasty, Balloon, Coronary↗
PubMed2000

Vascular oxidant stress early after balloon injury: evidence for increased NAD(P)H oxidoreductase activity.

Available evidence for oxidative stress after angioplasty is indirect or ambiguous. We sought to characterize the pattern, time course, and possible sources of free radical generation early after arterial balloon injury. Ex vivo injury performed in arterial rings in buffer with lucigenin yielded a massive oxygen-dependent peak of luminescence that decayed exponentially and was proportional to the degree of injury. Signals for injured vs. control arteries were 207. 1 +/- 17.9 (n = 13) vs 4.1 +/- 0.7 (n = 22) cpm x 10(3)/mg/min (p <. 001). Data obtained with 0.25 mmol/l lucigenin were validated with 0. 005-0.05 mmol/l lucigenin or the novel superoxide-sensitive probe coelenterazine (5 micromol/l). Gentle removal of endothelium prior to injury scarcely affected the amount of luminescence. Lucigenin signals were amplified 5- to 20-fold by exogenous NAD(P)H, and were >85% inhibited by diphenyliodonium (DPI, a flavoenzyme inhibitor). Antagonists of several other potential free radical sources, including xanthine oxidase, nitric oxide synthase, and mitochondrial electron transport, were without effect. Overdistension of intact rabbit iliac arteries in vivo (n = 7) induced 72% fall in intracellular reduced glutathione and 68% increase in oxidized glutathione, so that GSH/GSSG ratio changed from 7.93 +/- 2.14 to 0. 81 +/- 0.16 (p <.005). There was also 28.7% loss of the glutathione pool. Further studies were performed with electron paramagnetic resonance spectroscopy. Rabbit aortas submitted to ex vivo overdistension in the presence of the spin trap DEPMPO (5-diethoxy-phosphoryl-5-methyl-1-pyrroline-N-oxide, 100 mmol/l, n = 5) showed formation of radical adduct spectra, abolished by DPI or superoxide dismutase. Computer simulation indicated a mixture of hydroxyl and carbon-centered radical adducts, likely due to decay of superoxide adduct. Electrical mobility shift assays for NF-kappaB activation were performed in nuclear protein extracts from intact or previously injured rabbit aortas. Balloon injury induced early NF-kappaB activation, which was decreased by DPI. In conclusion, our data show unambiguously that arterial injury induces an immediate profound vascular oxidative stress. Such redox imbalance is likely accounted for by activation of vessel wall NAD(P)H oxidoreductase(s), generating radical species potentially involved in tissue repair.

Acridines↗
PubMed2000

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↗
PubMed1999

A case of association of duplication of the urogenital and intestinal tracts.

Report of the case of a Caucasian girl, presently 3 years old, who has been followed at the Pediatric Service of the Walter Cantidio Hospital (Federal University of Ceará; Fortaleza, Brazil) since she was 15 days old. At birth she presented a duplication of the bladder, urethra, external genitalia, vagina, colon, and rectum. No cardiac anomalies, bone deformities, or other congenital malformations were detected. When she was 16 months old the child underwent corrective surgery, with rectal vault reconstruction, placing a single and continent anal sphincter in its usual position and resection of the longitudinal vaginal septum, forming a single vaginal cavity. The surgery also resulted in a perineum of normal appearance. Presently, the patient is doing well.

Abnormalities, Multiple↗
PubMed1999

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↗
PubMed1998

Oxidized thiols markedly amplify the vascular response to balloon injury in rabbits through a redox active metal-dependent pathway.

OBJECTIVE: Our aim was to assess whether exposure to oxidized thiols--a known usual consequence of oxidant stress--has the potential to affect the vascular repair response to angioplasty-induced injury. In addition, we also assessed the role of redox active metals in disulfide effects. METHODS: In 82 rabbits submitted to overdistention of iliac arteries, the following variables were analyzed: neointimal thickening, immunoreactivity to Proliferating Cell Nuclear Antigen, and cellular and collagen densities. RESULTS: A single intraarterial challenge of oxidized glutathione (GSSG, 6.5 mumol/kg) during and immediately after injury triggered a marked increase of the vascular repair reaction, as follows: (A) at day 7 after injury, there was a 2.7-fold increase in proliferation (p < 0.001 vs. control); (B) at day 14, there was increase of intimal/medial area ratio to 1.35 +/- 0.14, vs. 0.56 +/- 0.08 in controls. Proliferating cells increased to 5.5 +/- 0.8 cells/mm2, vs. 2.2 +/- 0.5 in controls (p < 0.002 for both variables). Overall cellularity was enhanced 2.2-fold; (C) at day 28, there was ongoing vessel wall proliferation, contrarily to controls. All GSSG effects were completely prevented by co-infusion of reduced glutathione (GSH) and were mimicked by cystine (6.5 mumol/kg). The uninjured artery showed no response to disulfides. To assess the role of redox active metals in GSSG action, the effects of 1,10-phenanthroline or N-CBZ-Pro-Leu-Gly hydroxamic acid (HXA), metal chelators with metalloproteinase inhibitor properties, were evaluated. Both compounds totally blocked the GSSG-induced amplification of vascular responses. In rabbits not exposed to GSSG, HXA decreased neointimal thickening by 50% (p < 0.05). CONCLUSIONS: Exposure to excess disulfide levels early after vascular balloon injury markedly amplified the late cellular response through interaction with redox active metals. These pathways can potentially mediate noxious effects of oxidative stress in vessels.

Animals↗
PubMed1997

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↗
PubMed1994

[Myocardial infarction in infective endocarditis].

Two patients with chronic valvular heart disease and myocardial infarction were assisted at our hospital. Both of them were febrile and only one had petechiae associated with signs of valvular involvement led to suspicion of infective endocarditis. Although blood cultures were negative, echocardiographic, surgical and anatomopathologic findings were compatible with infective endocarditis. They required cardiac surgery during the acute phase of the infection because they presented progressive hemodynamic deterioration and no satisfactory response to antimicrobial regimen too. One patient died at late follow-up (two weeks after the hospital discharge) and the other survived, but with signs of cardiac failure (class II of NYHA) one year after the procedure.

Adolescent↗
PubMed1994

[Radiologic signal of dehiscence of Starr-Edwards aortic prosthesis].

A male 54 years-old patient with infective endocarditis through Staphylococcus aureus with prosthesis of Starr-Edwards aortic with clinical and echocardiographic signs compatible with dysfunction classified as severe. The x-ray images presented double silhouette of the prosthesis, thus suggesting its partial dehiscence. This case report points out that the detailed analysis of the X-ray may supply relevant data for the diagnosis of one of this complication thus influencing on management and prognosis.

Aortic Valve↗
PubMed1993

In-vitro and in-vivo studies of the decrease of amphotericin B toxicity upon association with a triglyceride-rich emulsion.

The effects of amphotericin B associated with a triglyceride-rich emulsion (AB-emulsion), shown previously to behave like lymph chylomicrons, were evaluated in vitro and in vivo. Incorporation of amphotericin B to the emulsion was monitored by UV-visible spectrophotometry. Whilst conventional amphotericin B induced a considerable K+ efflux from erythrocytes, AB-emulsion had essentially no effect. In contrast, the K+ efflux from Candida albicans was similar upon incubation either with AB-emulsion or with conventional amphotericin B. Administration to rats showed reduced mortality due to AB-emulsion compared with conventional amphotericin B. Renal toxicity was also decreased upon AB-emulsion treatment, as evaluated by serum urea and creatinine levels. These data suggest that chylomicron-like emulsions could be utilized as vehicles for amphotericin B in antifungal therapy.

Amphotericin B↗
PubMed1992

Late results (50 to 182 months) of the Jatene operation.

Between May 1975 and August 1991, 184 patients with transposition of the great arteries (TGA) were operated upon by Jatene operation. One hundred and sixteen underwent corrective surgery prior to June 1987 with a follow-up period of between 50 and 182 months. The ages of these 116 patients ranged from 1 day to 84 months (11.53 +/- 15.98). Eleven percent were less than 1 month old, 38% were between 1 and 6 months, 29% between 7 and 12 months and 22% were older than this. Eighty-eight patients (76%) were boys and the weight ranged from 2.4 to 17.0 kg (6.39 +/- 3.38). Thirty-eight patients (20.7%) died in the immediate postoperative period. Of the survivors, 5 died in the late follow-up between 9 and 66 months (endocarditis at 9 and 66 months; gastroenteritis at 20 months; sudden death at 48 months; and during reoperation for relief of pulmonary stenosis (PS) at 60 months). Of the surviving 73 patients, 24 (32.9%) are anatomically normal at a mean period of 92.5 months postoperatively. Twenty-two (30.1%) have dysfunctions without clinical repercussion. Nineteen (26%) have had no recent evaluation and 8 (11%) were submitted to reoperation or angioplasty for relief of PS. Ninety-eight percent of the patients have normal left ventricular function. The majority of the patients surviving 50 to 182 months are in good clinical condition and if dysfunctions are present these show no progression or severe hemodynamic alterations.

Child↗