Biomedical subjects

M A Pereira

Publications and source records attributed to M A Pereira.

At least 19 recordsLinked to original sources

PubMed1992

Biologic markers in hospital workers exposed to low levels of ethylene oxide.

Operators of hospital sterilizers that use ethylene oxide were studied to determine if there was a relationship between exposure and a battery of biological markers. A total of 73 workers from nine hospitals in the United States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide exposure during four months prior to collection of peripheral blood. The frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S. subjects when controlling by regression analysis for various confounding factors, including cigarette smoking. Hemoglobin adducts, but not SCEs, were also increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no consistent relationship with exposure. The U.S. study participants were classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide exposure. The group with an exposure of greater than 32 ppm-h had an increased frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA) exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was 0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for SCEs. The latter finding may have been due to longer shipping times for the specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/- 0.08 ppm. This study is the third to suggest that exposures less than the U.S. OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is not known whether these changes may be indicative of increased risk of disease; however, they do appear to reflect exposure to relatively low levels of ethylene oxide. The exact meaning of these changes is unknown.

Adult↗

PubMed1992

[Value of transesophageal echocardiography in the diagnosis of acute aortic dissection].

We describe our experience of six patients with clinical suspicion of acute aortic dissection (AAD) who were studied consecutively by transesophageal echocardiography (TEE) from April to July of 1991. All of them were previously submitted to transthoracic echocardiogram. The diagnosis was correctly established by TEE in five cases, confirmed by aortography and/or surgery (four cases), or by autopsy (one case). In one patient the diagnosis of AAD was excluded by TEE, and posteriorly by nuclear magnetic resonance. Four patients had a Stanford type A, and one patient a type B dissection. The site of entry was identified in three cases; the intimal entry tear of the type B dissection, not observed by TEE, was localized in the aortic arch by aortography. In three of the four type A dissection cases, a thrombus in the false lumen and an aortic regurgitation were found. No other noninvasive methods were used after the diagnosis of AAD by TEE. The surgical repair was successful in three cases, one of which, without previous necessity of aortography. In our experience, TEE increased extraordinarily the diagnosis efficacy of AAD, making possible an earlier therapeutic approach, and probably contributing to the improvement of the prognosis of this pathology.

Acute Disease↗

PubMed1991

Prevention by chemopreventive agents of azoxymethane-induced foci of aberrant crypts in rat colon.

Foci of aberrant crypts are putative preneoplastic lesions of colon cancer that can be detected in unsectioned colons stained with methylene blue. The ability of this assay to demonstrate chemopreventive activity was evaluated. Male Sprague-Dawley rats received two subcutaneous injections 1 week apart, of 15 mg/kg azoxymethane each. The animals started to receive the test agents in their diet 1 week prior to the first injection of azoxymethane and continuously until killed 5 weeks later. The number of foci of aberrant crypts induced by the treatment of azoxymethane was reduced from 228 foci/animal without any chemopreventive agent to 151 foci/animal by N-acetylcysteine; to 121 foci/animal by dehydroepiandrosterone; to 161 by alpha-difluoromethylornithine; and to 121 by 1,2-oxothiazolidine-4-carboxylate. The other agents (diallyl sulfide, ellagic acid and phenethyl isothiocyanate) did not significantly alter the number of foci/animal induced by azoxymethane. Animals that did not receive azoxymethane had an average of 0.72 foci/animal. Our results suggest that four of the tested agents might reduce azoxymethane-induced colon cancer, which requires confirmation. Further validation of the foci of aberrant crypt in the colon assay to screen chemicals for chemoprevention agents is warranted.

Acetylcysteine↗

PubMed1991

Screen of five alkyl carbamates for initiating and promoting activity in rat liver.

Five alkyl carbamates, methyl, ethyl, propyl, hydroxypropyl and ethylhexyl, were tested for initiating and promoting activity in rat liver. The test for initiating activity consisted of administering the carbamate by gavage to male Sprague--Dawley rats at either 6 or 18 h after a 2/3 partial hepatectomy. One week later, the rats received 500 ppm sodium phenobarbital in their drinking water until killed 10 weeks later. None of the carbamates at 1/5 the LD50 induced gamma-glutamyltranspeptidase (GGT)-positive foci, indicating the lack of initiating activity. The tumor promoting activity test consisted of initiation with 80 mmol/kg diethylnitrosamine administered 18 h after a partial hepatectomy. One week later, the rats received one of the the carbamates at either 1/10 or 1/20 the LD50 5 days per week until sacrificed 10 weeks later. The alkyl carbamates increased the volume of the foci, the percent of the liver occupied by the foci, the number of foci/cm3 (except ethylhexyl carbamate), and the number of foci/liver (except ethylhexyl carbamate). These results suggest that the alkyl carbamates are tumor promoters and not tumor initiators in rat liver.

Animals↗

PubMed1991

[Transcutaneous pacemaker in cardiovascular emergencies].

UNLABELLED: OBJECTIVES AND DESIGN OF THE STUDY: Retrospective study to evaluate the efficacy and tolerance of the transcutaneous cardiac pacemaker in the urgent treatment of asystole or severe bradycardia. SETTING: Coronary Care Unit (CCU) and emergency area of the central reference Hospital. PATIENTS: 24 patients, 20 males and four females, aged between 57 and 84 years (mean 70.4 +/- 7.9). Five pts were in asystole and 19 in severe bradycardia. INTERVENTIONS: The transcutaneous pacemaker used, was the "Cardio Aid Zoll NTP" model. The intensity of the electrical stimulation was increased progressively, until electrical capture or intolerable discomfort by the patients was achieved. We defined by electric efficacy, the visualization of pacing spike followed by a deflection due to ventricular depolarization; and by hemodynamic efficacy, the evidence of myocardial contraction, defined as a palpable pulse, synchronous with the pacing artefact. MAIN RESULTS: Stimulation threshold ranged from 30 to 140 mA (mean 67.7 +/- 23.4). The duration of pacing was from 15 minutes to 13 hours, being more than one hour in only four situations. From the 20 conscious patients, or the ones who got conscious, 15 (75%) tolerated well the stimulation. It was intolerable in five pts (25%). No significative side effects due to the use of transcutaneous pacemaker were observed. CONCLUSIONS: The transcutaneous pacemaker was efficient in the electric and hemodynamic stabilization in the majority of patients. It was generally well tolerated and without important side effects. We think that it may be a valid alternative to transvenous pacing technics in the treatment of asystole and severe bradycardia situations.

Aged↗

PubMed1991

[Asymptomatic aortic dissection with large aneurysm of the ascending and the transverse aorta. Report of a case].

The authors present a cae of asymptomatic type I of the DeBakey aortic dissection with a voluminous aneurysm of the false channel. In the absence of suggestive symptoms, the diagnosis was established by chance through two dimensional echocardiography and later confirmed by magnetic resonance imaging. They ignore the period of time between the beginning of the dissection and the diagnosis, but they consider that it could have exceeded five years. During that time, besides as well tolerated aortic incompetence and aneurysmatic enlargement of the false channel, no other problems were detected. Based on this case, the authors are going through the literature and are discussing the importance of some noninvasive imaging techniques in the diagnosis and follow-up of this patients.

Aortic Dissection↗

PubMed1991

[Indirect criteria of coronary reperfusion and permeability in patients with acute myocardial infarction who have received thrombolytic therapy].

OBJECTIVE: To evaluate the value of some indirect reperfusion signs (IRS) as markers of coronary artery patency in patients (PTS) with acute myocardial infarction (AMI) submitted to intravenous (IV) thrombolytic therapy (TT). DESIGN: Retrospective study, with analysis of the sensibility (S), specificity (SP) and predictive value (PV) of three IRS: 1. Pain and ST resolution in the first three hours; 2. Peak CK in the first 13 hours; 3. accelerated idioventricular rhythm (AIVR) in the first three hours. SETTING: Coronary Care Unit (CCU) of the Santo António Hospital and Hemodynamic Laboratory of the S. João Hospital, Oporto. PATIENTS: Sixty seven PTS (mean age 53.4 +/- 10.6 years) with confirmed AMI, 62 male and five female, 34 with anterior and 33 with inferior infarction, TT started in the first three hours of the beginning of symptoms in 34 PTS and from three to six hours in 33 PTS, all submitted to coronary angiography in the hospital setting (7.6 +/- 5.9 days after AMI). INTERVENTIONS: IV administration of 1,500,000 U of streptokinase (SK) in 47 PTS and 30 U of APSAC in 20 PTS, preceded by 200 mg IV prednisolone and oral 100 mg acetilsalicylic acid, and followed by IV heparin therapy. Continuous electrocardiographic monitoring, and serial 12 leads ECG and enzymatic assays (at start and 1, 3, 7, 13 and 25 hours of TT). Analysis of the correlation of the three IRS (isolated and in association) with coronary artery patency (TIMI 2 or 3). MEASUREMENTS AND RESULTS: The total patency rate was 79.1%; there was no statistically significant difference with regard to AMI location, time of symptoms onset (0-3 vs 3-6 hours) or thrombolytic agent (SK vs APSAC). The first and second IRS had a high S and a low SP; together S = 79.2%, SP = 64.3% and PV = 89.4%. The third IRS with the first and/or the second one had a low S (about 25%) but SP and PV of 100%. The coronary patency rate of PTS without IRS was always greater than 50%. CONCLUSIONS: The analysed IRS although not very reliable are useful when considered in association. It is possible to assess PTA with high probability of reperfusion if AIVR is present. The absence of IRS does not exclude coronary artery patency. There is still missing more reliable no-invasive reperfusion markers.

Adult↗

PubMed1990

Inhibition of leukocyte chemotaxis by serum factor in diabetes mellitus: selective depression of cell responses mediated by complement-derived chemoattractants.

Rat neutrophil chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene (LT) B4, and lipopolysaccharide-activated serum (LPS-AS) were quantitatively assessed using the micropore filter system. Cells were suspended in either normal or diabetic rat serum for testing. Diabetic donor serum did not affect migration of neutrophils in a concentration gradient of the synthetic chemotactic agents. In contrast, the migratory responses to LPS-AS were significantly less than normal in this circumstance. Summation of effects was observed when FMLP and LPS-AS, or LTB4 and LPS-AS were simultaneously added to the test chamber, with cells suspended in normal serum. Suspended in diabetic rat serum neutrophils responded normally to the synthetic chemoattractants but the response to the activated serum was blocked. Cells previously incubated in the presence of diabetic donor serum then transferred to a culture medium for testing, presented reduced migratory responses to LPS-AS. Supramaximal, inhibitory concentrations of FMLP and LTB4, did not influence the response of neutrophils to LPS-AS. In vivo, suppression of cellular emigration to an inflamed area was observed from the early stages of the diabetic state. The inhibitory activity of chemotaxis in diabetes mellitus was previously reported to be associated with a protein factor in plasma of the animals. It is suggested that the inhibitory factor of chemotaxis in diabetes mellitus interacts with neutrophil receptors for complement-derived chemoattractants to induce blockade of cell-oriented locomotion either in vitro or in vivo.

Amino Acid Sequence↗

PubMed1990

Polyclonal activation of B lymphocytes during experimental infection with Schistosoma mansoni.

A significant polyclonal activation of B lymphocytes was observed during experimental infection of C57BL/10J mice with Schistosoma mansoni. The isotypic pattern of this expansion, assessed by the Protein-A plaque-forming cell method, was compared with and found to differ from those occurring after infection by Trypanosoma cruzi or injection of bacterial LPS. In the infection of S. mansoni an early expansion of most immunoglobulin isotypes occurs together with a late, sustained expansion of IgG1-secreting cells. High levels of polyclonal B cell activation were observed after adoptive transfer of spleen cells from infected mice to isogenic recipients pre-treated with hydroxyurea.

Animals↗

PubMed1989

Comparison of the effects of acute and subacute treatment of phenobarbital in different strains of mice.

A strain specificity has been demonstrated for the effect of subsequent administration of phenobarbital (PB), in which diethylnitrosamine (DENA)-initiated hepatocarcinogenesis was promoted in C3H mice, inhibited in B6C3F1 (C57BL x C3H) and not affected in C57BL mice. A correlation has been established between the ability of barbiturates and hydantoins to promote tumor formation and their ability to induce liver growth, hepatic DNA synthesis and mixed function oxidase activities. Therefore, we examined in these 3 strains of mice and in C3B6F1 (C3H x C57BL) mice the effect of PB administered in their drinking water for 4 days or 28 days. The liver weight to body weight ratio was increased by PB in all types of mice. Microsomal protein concentrations were increased in C57BL mice after 28 days of treatment, in C3H after both 4 days and 28 days and in B6C3F1 after 4 days of treatment. No effect upon microsomal protein content was observed in C3B6F1 mice. DNA content was increased in C3H mice, both in the 4-day and 28-day treatment groups, while the other strains showed either a decrease or no difference from control. DNA synthesis was elevated in all strains of mice after 4 days of treatment with PB, however, after 28 days of treatment there was either a much reduced increase (C57BL and C3B6F1) or no difference (C3H and B6C3F1) from controls. In all 4 types of mice after 4 and 28 days of treatment, PB increased the concentration of cytochrome P-450, the activity of aminopyrine-N-demethylase (AmDm) and 7-ethoxyresorufin-O-deethylase (ErDe) and the oxidation of testosterone (T). The oxidative metabolites of T were similar in the 4 types of mice.

Aminopyrine N-Demethylase↗

PubMed1989

Chloroform-induced multiple forms of ornithine decarboxylase: differential sensitivity of forms to enhancement by diethyl maleate and inhibition by ODC-antizyme.

The role of glutathione (GSH) and ornithine decarboxylase-antizyme (ODC-AZ) in the regulation of the chloroform-mediated stimulation of rat hepatic ornithine decarboxylase (ODC) was investigated. We have previously implicated roles for each while examining the chloroform effect on crude cytosolic enzyme preparations. In this study we examined the effect of pretreatment with diethyl maleate (DEM), a GSH-depleting agent, on the chloroform stimulation of the two forms of the rat hepatic ODC enzyme and the sensitivity of these two forms to inhibition by the ODC-AZ. While the pretreatment with DEM provided a greater amount of the two forms of the ODC enzyme, it also resulted in a differential stimulation of each form when compared to chloroform alone. Additionally, Peak II was 20-25% more sensitive to the same amount of ODC-AZ then Peak I ODC activity.

Animals↗

PubMed1989

Strain differences in hepatic tumor promotion by phenobarbital in diethylnitrosamine- and dimethylnitrosamine-initiated infant male mice.

The effects of phenobarbital (PB) on hepatocellular carcinogenesis in three strains of nitrosamine-initiated infant male mice were evaluated. Fifteen-day-old C57Bl/6NCrlBR (C57Bl), C3H/HeNCr1BR (C3H) and B6C3F1 mice were treated with a single i.p. injection of either diethylnitrosamine (DENA) (5 micrograms/body wt), dimethylnitrosamine (DMNA) (5 micrograms/body wt) or saline. One-half of the treated mice received PB via the drinking water (500 mg/l) for 24 weeks. The remaining treated mice were given deionized drinking water. Mice were killed at 28 weeks of age and hepatic lesions were evaluated. Only animals that received DENA or DMNA exhibited tumors. C3H mice treated with DENA + PB demonstrated a significant increase in hepatic adenoma number compared to C3H mice exposed to DENA only. Conversely, B6C3F1 males treated with DENA + PB exhibited a significant decrease in the number of hepatic adenomas compared to B6C3F1 males treated with DENA alone. No change was noted in adenoma size in B6C3F1 mice treated with DENA + PB from those receiving DENA only. Chronic PB exposure of C57Bl males previously treated with DENA had no effect on hepatic adenoma number or size. C3H mice treated with DMNA + PB displayed an increase in both adenoma size and adenoma number compared to C3H mice receiving DMNA only. Similarly, in B6C3F1 mice, PB treatment increased both the adenoma incidence and adenoma number in DMNA initiated mice. PB had no effect on hepatic adenoma incidence or number in DMNA-treated C57Bl mice. These data suggest that the ability of PB to promote hepatic tumorigenesis in the 15-day-old initiated mouse is dependent on both the strain of the mouse and the initiating chemical carcinogen.

Animals↗

PubMed1989

Chloroform inhibition of 1,2-dimethylhydrazine-induced gastrointestinal tract tumors in the Fisher 344 rat.

The effect of chloroform (CHCl3), administered at 0, 900, and 1800 mg/liter in the drinking water, on the carcinogenic potency of 1,2-dimethylhydrazine (DMH) was investigated. Groups of 40 male Fisher 344 rats were given one of the three drinking water solutions for 39 weeks following the subcutaneous injection of 200 mg/kg DMH, a known gastrointestinal (GI) tract carcinogen in this animal strain. When tumors from the GI tract were pooled there was a highly significant (p less than 0.001) decrease in total number of tumors per group with increasing concentration of drinking water CHCl3. In the control group (0 mg/liter CHCl3), 14/39 (36%) of the animals developed tumors of the GI tract, including the duodenum, jejunum, stomach, cecum, and colon. In contrast, the incidence of tumors in the two groups of rats given CHCl3 in the drinking water was significantly lower (p less than 0.001; 900 mg/liter CHCl3, 12.8%; 1800 mg/liter CHCl3, 12.5%). A similar relationship was obtained when colon tumors were analyzed independently (p = 0.01). The incidence of total colon tumors obtained in the control group of this study (10/39, 26%) agrees well with the previous study by B.S. Reddy, K. Watanabe, and J.H. Weisburger (1977, Cancer Res. 37, 4156-4159) conducted in the same rat strain (7/30, 23%). These results demonstrate that CHCl3 in the drinking water inhibits carcinogenesis in the rat GI tract.

1,2-Dimethylhydrazine↗

PubMed1988

Chloroform induction of ornithine decarboxylase antizyme (ODC-AZ) in male rat liver.

Chloroform stimulation of rat hepatic ODC is most dramatic at 18 h following a single injection. Repeated dosing, 1 dose/d for up to 7 d, results in a daily decline in the ability of the liver enzyme to respond 18 h after the final injection. We postulated that this decline was due to an increased synthesis and accumulation of the OCD-AZ protein. ODC-AZ was determined by measuring the inhibition of isolated ODC activity as described by Hayashi and Fujita and modified in our laboratory to use kidney ODC. Male and female Fischer 344 rats were injected daily for 1, 3, or 7 d with 3.0 mmol/kg chloroform. Chloroform induced ODC-AZ activity in males at 3 and 7 d (26% and 37% inhibition of the ODC activity in the incubation medium, respectively). While females exhibited a similar decline in ODC activity after repeated doses, ODC-AZ was not induced. Thus, it would appear that daily exposure of rats to chloroform results in a refractoriness of its induction of ODC activity accompanied by an induction of the ODC-AZ in males. However, in females these two responses were not directly related.

Animals↗

PubMed1988

Dose-response relationship of diethylnitrosamine-initiated tumors in neonatal balb/c mice: effect of phenobarbital promotion.

The dose-response of diethylnitrosamine (DENA) initiation of hepatocarcinogenesis was determined in infant Balb/c male mice with and without subsequent phenobarbital treatment. Male Balb/c mice received a single intraperitoneal injection of DENA (0, 2.5, 10.0, 25.0 or 50.0 micrograms/gbw) in saline on day 15 of age. Ninety mice were treated at each dose level. At weaning, mice received either deionized drinking water (45 mice per group) or deionized drinking water containing 500 mg/L sodium phenobarbital (PB) (45 mice per group). Mice from each group were sacrificed 12, 24, and 40 weeks post-weaning. Liver and lung tumors were found in DENA-only-treated and DENA + PB-treated mice. In DENA-only-treated mice, the incidence and number of hepatic adenomas were similar (not dose-dependent) at DENA doses of 10, 25, and 50 micrograms/gbw at each of the 3 sampling times. DENA-only-treated mice did display a time-related increase in hepatic adenoma incidence and number at each dose. In PB-treated mice, the hepatic adenoma number was dependent upon the dose of DENA between 2.5 and 50 micrograms/gbw. PB treatment following DENA administration resulted in a decrease in the time required for the detection of hepatic adenomas and increased the number of hepatic adenomas at most sampling times compared to the mice that received DENA only. Hepatocellular carcinomas (HPC) were detected in mice receiving the highest DENA doses (25 and 50 micrograms/gbw). PB treatment increased the number and incidence of HPC and decreased the time of first detection of HPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1988

Quantitative and qualitative immunohistochemical detection of myc and src oncogene proteins in normal, nodule, and neoplastic rat liver.

This study examined the possibility of using an immunohistochemical technique to detect the expression of myc and src oncogene proteins (ops) in livers of male Sprague-Dawley rats after treatment with the carcinogen diethylnitrosamine (with or without phenobarbital promotion) or untreated. We found that the majority of nodules and tumors from these livers stained for myc and src ops, indicating that myc and src expression did occur in these structures. These results were expected, since myc and src expression has been previously observed by others using different techniques. However, in our study, myc and src op staining was also noted in normal liver areas from rats in any of the four treatment groups (DENA, DENA + PB, PB alone, or untreated). The staining pattern of normal liver was different for each oncogene probe but was consistent within the four groups. In most cases, oncogene expression of normal liver occurred at sites of abnormal (but non-neoplastic) hepatocytes. The method reported here used both a qualitative technique of op expression analysis and a quantitative method using a Zeiss computer-driven image analysis system.

Animals↗

PubMed1988

Tolerance induction and immunological priming initiated by mucosal contacts with protein antigens in inbred strains of mice.

1. We show that mouse strains differ widely in susceptibility to tolerance induction and/or immunization (priming) following contact of protein antigens (ovalbumin, human or bovine gamma globulins) with different mucosal surfaces. 2. When compared to a control group pretreated with saline, mice pretreated by the oral (intragastric) route with antigen became significantly less responsive to subsequent parenteral immunization (i.e., tolerant). This was observed in most, but not all, antigen/strain combinations. 3. Similar, although less prominent changes were induced by pretreatments with antigen by the ocular (conjunctival) route. 4. No significant effects were observed following pretreatments by the nasal, vaginal or rectal routes. 5. Genes present in strains selected for multispecific "high" or "low" responsiveness are included among those involved in tolerance induction following mucosal contacts with protein antigens.

Animals↗

PubMed1988

Chloroform mediated refractory state against ornithine decarboxylase induction by serial chloroform treatment.

The chloroform mediated refractory state against ornithine decarboxylase induction in male and female rat liver was further studied. One aspect of the investigation was to determine the duration of the induced refractory period while the other component focused on the extent to which the inhibitory effect was dependent upon the concentration of the first dose. When the dosing interval between the first and second dose was varied from 1 to 31 days, the magnitude of the resistance to further stimulation by chloroform only decreased gradually. In studies where the concentration of the first dose was varied while the dosing interval was fixed, it was concluded that the extent of the inhibitory effect was dependent upon the concentration of the first dose.

Animals↗