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Biomedical subjects

J Pinto

Publications and source records attributed to J Pinto.

At least 73 records · Page 4Linked to original sources
PubMed1990

Enhanced depletion of lens reduced glutathione Adriamycin in riboflavin-deficient rats.

The anticancer drug Adriamycin has photosensitizing properties which potentially may be detrimental to lens tissue. Since reduced glutathione (GSH) serves to protect lens from photo-oxidative stress and dietary riboflavin is required by glutathione reductase to regenerate GSH, we investigated whether Adriamycin intensifies the depletion of GSH levels in rat lens during dietary riboflavin deficiency. Three-week-old rats were divided into two groups. One group was fed a diet deficient in riboflavin (less than 1 ppm) and the other group was pair-fed a control diet containing adequate riboflavin (8.5 ppm). After 6-12 weeks of dietary treatment, half the animals in each dietary group received Adriamycin (8 mg/kg/day) intraperitoneally for 3 days. After killing the rats, lenses were removed, and GSH content and glutathione reductase activity were measured in freshly prepared homogenates. To determine the extent of systemic oxidative stress and the degree of riboflavin deficiency, glucose-6-phosphate dehydrogenase and glutathione reductase activities, respectively, were measured in erythrocytes. In lens of rats fed the riboflavin-sufficient diet, treatment with Adriamycin did not diminish GSH content or alter glutathione reductase activity. In confirmation of reports by others, lenses of animals fed the riboflavin-deficient diet had diminished GSH levels, lower basal glutathione reductase activity, and elevated glutathione reductase activity coefficients compared to those of animals pair-fed the control diet. The present study shows that in riboflavin-deficient rats, Adriamycin exacerbated the depletion of GSH but did not reduce further glutathione reductase activity. The implications of these findings are that nutritional deficiencies, in particular riboflavin deprivation, may pose a potential risk to lenticular tissue following Adriamycin treatment.

Animals↗
PubMed1990

White matter necrosis in very low birth weight infants: neuropathologic and ultrasonographic findings in infants surviving six days or longer.

We describe the neuropathologic and ultrasonographic findings in 22 very low birth weight infants (mean weight 948 gm) who survived at least 6 days and for whom cranial ultrasonography had been performed three or more times in life. White matter necrosis was found in 15 of the 22 subjects and was judged chronic (5 days' duration or longer) in seven subjects. The most common pattern was diffuse necrosis of hemispheric white matter, found in 10 of 15 infants; restriction of necrosis to the periventricular region was found in only three infants. The classic histologic features of periventricular leukomalacia were absent from 7 of the 15 infants with necrosis. Seventeen infants had intraventricular hemorrhage, but extension of ventricular blood into white matter unaffected by infarction was not found. Two ultrasonographic features were associated with white matter necrosis: increased parenchymal echogenicity and ventricular enlargement. One or both of these findings were present in 67% of infants with white matter necrosis, in 90% of infants with diffuse necrosis, but in no infant without necrosis. Increased parenchymal echogenicity was seen in all four infants with hemorrhagic necrosis, in 60% of infants with diffuse necrosis, but in none of the five infants with localized necrosis. We conclude that the very small infants now dying in nurseries have a form of white matter damage that is more extensive than, and in some cases histologically different from, periventricular leukomalacia as originally described. Ultrasonography as used in this study identified most but not all infants with pathologically verified white matter necrosis.

Brain↗
PubMed1990

Neonatal cranial ultrasound abnormalities: association with developmental delay at age one in low birth weight infants.

Relationships between abnormalities on neonatal serial cranial ultrasound and cognitive development at age one year were examined in 153 low birth weight (LBW) infants. Infants with complex injury (persistent parenchymal echogenicity, lucency, or persistent ventricular enlargement) scored significantly lower on the Bayley Mental Development Index than noninjured infants. Nine of 11 infants with complex injury had severe developmental delay in contrast to 3/110 of the noninjured. Adjusting for birth weight, gestational age, head circumference and social class, infants with complex injury were 33 times more likely to be severely delayed than noninjured infants. Risk for severe delay associated with LBW appeared to be indirect, through increased probability of ultrasonographic abnormality. The poorest developmental outcome was seen in infants with both complex perinatal brain injury and either very LBW or very young gestational age. However, very LBW infants with normal neonatal ultrasounds were at negligible risk for severe delay at age one.

Birth Injuries↗
PubMed1990

The MMPI and Jesness Inventory as measures of effectiveness on an inpatient conduct disorders treatment unit.

There is a paucity of research on the effectiveness of inpatient treatment of conduct disorders. The purpose of the present study was to determine what effect a locked behavioral/cognitive treatment setting would have upon the Minnesota Multiphasic Personality Inventory (MMPI) and Jesness Inventory scores of adolescent inpatients. Fifty consecutive admissions (30 males, 20 females) to a conduct disorders unit were administered the MMPI and Jesness Inventory pre- and posttreatment. Statistically significant changes were found on both inventories. Males responded to treatment more favorably than did females. Improvement on the test scores could not conclusively be linked to the treatment due to the absence of a control group; however, combined with previous research, the results indicate areas of improvement in the sample's pathology.

Adolescent↗
PubMed1988

Inhibition of flavin metabolism by adriamycin in skeletal muscle.

Adriamycin (ADR), a potent antineoplastic agent, has been shown to interact with flavin derivatives and to compete with flavin coenzymes for their respective binding sites on flavin-containing enzymes. The present investigation determined that ADR administration inhibited flavin adenine dinucleotide (FAD) biosynthesis from riboflavin in rat skeletal muscle in a dose-related manner compared to results in pair-fed controls. Five groups of adult Holtzman rats of both sexes were given twice daily intraperitoneal injections of ADR for 3 days, representing cumulative doses of 6, 12, 18, 24, and 30 mg/kg body weight. At the cumulative dose of 6 mg/kg, there was no significant effect, but at 12, 18, 24, and 30 mg/kg levels significant increases in [14C]FAD formation from [14C]riboflavin occurred. ADR-induced myopathy may be due, at least in part, to inhibition of FAD formation, ultimately leading to changes in energy metabolism and oxidative capacity.

Animals↗
PubMed1988

Riboflavin deficiency and glutathione metabolism in rats: possible mechanisms underlying altered responses to hemolytic stimuli.

Riboflavin deficiency suppresses parasitic growth in malaria. Three possible mechanisms have been proposed previously to explain the survival advantage of riboflavin-deficient hosts: a) enhanced fragility of red blood cells (RBC), b) decreased formation of reticulocytes and/or c) decreased concentrations of reduced glutathione (GSH) and ATP. The validity of these proposed mechanisms was tested by investigating whether riboflavin deficiency alters the hemolytic response to three stimuli: hydrogen peroxide (H2O2), a hypotonic medium or ferriprotoporphyrin IX (FP). Reticulocyte counts and concentrations of ATP and GSH were also determined. The percentage of hemolysis induced by H2O2 or FP was significantly less in riboflavin-deficient than in control animals. By contrast, hemolytic response to a hypotonic medium was enhanced during riboflavin deficiency. Despite diminished activity of glutathione reductase and normal glutathione peroxidase activity during riboflavin deficiency, the erythrocyte concentration of GSH was increased over that in control animals. Concentrations of ATP and hemoglobin in erythrocytes as well as the reticulocyte count were unaltered during riboflavin deficiency. Thus, diminished malarial parasitemia in riboflavin-deficient animals occurs despite greater resistance of RBC to either H2O2- or FP-induced hemolysis, and in the presence of a normal reticulocyte count and erythrocytes ATP concentration. Results of this study raise the possibility that Plasmodium parasites have greater requirements for flavin coenzymes, GSH or ATP than those of host erythrocytes, which may explain the apparent protection of the riboflavin-deficient host from malaria.

Adenosine Triphosphate↗
PubMed1988

Interobserver variability in neonatal cranial ultrasonography.

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.

Cerebral Hemorrhage↗
PubMed1988

Enhancement of adriamycin-induced mortality during riboflavin administration and riboflavin deficiency in rats.

Adriamycin-treated rats were monitored for survivorship while consuming a normal diet adequate in riboflavin, a normal diet and receiving daily high-dose injections of riboflavin-5'-phosphate (flavin mononucleotide, FMN), or a riboflavin-deficient diet. Each animal was compared to a corresponding pair-fed, saline-treated control. In Adriamycin-treated rats fed the normal chow diet alone, survivorship declined within 7 days and remained constant after 12 days to about 50%. Adriamycin-treated rats consuming the normal diet and injected with FMN initially showed similar survivorship; however, after 20 days survival fell to 14%. Adriamycin-treated, riboflavin-deficient rats showed within 5 days a precipitous decline in survivorship which leveled to 5%. These results suggest that during Adriamycin treatment, proper riboflavin nutriture may be a crucial determinant of survival.

Animals↗
PubMed1987

Pulmonary toxicity of a combination of low-dose doxorubicin and irradiation for inoperable lung cancer.

In 1980, 27 patients with inoperable lung cancer (26 non-oat cell, one oat cell) were treated by split-course irradiation (40 Gy/10 fractions) plus concomitant low-dose chemotherapy (doxorubicin 10 mg/m2). Twenty-four of the 27 patients received the entire treatment course. Fifteen of the 27 patients were administered various chemotherapy protocols after a period of one month. Median survival was 16 weeks despite a 60% response rate. The lungs were the main site of complications (13 cases of radiation pneumonitis for the 24 patients), which occurred primarily when an objective response was obtained. These complications partially explain the poor results. Injection of doxorubicin during irradiation appears to have been a determining factor.

Adult↗
PubMed1987

Disturbances in the formation of FAD and covalently bound flavins in Novikoff hepatoma from riboflavin-deficient rats.

The incorporation of radiolabeled riboflavin into flavin mononucleotide, flavin adenine dinucleotide, and flavin covalently bound to protein was determined in Novikoff hepatoma grown in both riboflavin-deficient and normal chow-fed rats. In Novikoff hepatoma, the incorporation of [14C]riboflavin into covalently bound flavins relative to that into FAD was substantially greater than that in host liver, and the turnover rate of riboflavin was also accelerated in tumor compared with the liver. The magnitude of incorporation of [14C]riboflavin into each of the various flavin fractions was substantially greater in tumors from riboflavin-deficient animals than in tumors from control animals. These data support the hypothesis that in conditions of riboflavin deprivation, Novikoff hepatoma maintains the levels of the physiologically important flavin coenzymes at the expense of the free riboflavin fraction. The incorporation of riboflavin into covalently bound flavins relative to that into FAD is substantially greater in Novikoff hepatoma than in liver. Accordingly, covalently bound flavins are either present in greater amounts or regulated differently in tumor than in normal tissue. Because the flavin moiety cannot be reutilized, the covalently bound flavin fraction in Novikoff hepatoma theoretically should be able to sequester riboflavin and thereby deplete the body reserves of this vitamin when dietary intake is marginal.

Animals↗
PubMed1987

Contact dermatitis to Hirudoid cream.

31 patients allergic to Hirudoid cream were patch tested with the ingredients. 29 were allergic to the cream base and 16 to one or more components. The most common allergens were myristyl alcohol, cetostearyl alcohol and parabens. 14 patients reacted only to the base. The results are discussed.

Dermatitis, Contact↗
PubMed1987

Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide.

Chronic alcoholism is associated with a high prevalence of riboflavin deficiency. Experiments were designed in an animal model to determine whether ethanol alters selectively the absorption of riboflavin and flavin adenine dinucleotide (FAD), the predominant dietary form of the vitamin. Rats received by gavage a liver homogenate to which either [14C]riboflavin or [14C]FAD was added with either ethanol or isocaloric sucrose solutions. Ethanol markedly diminished the bioavailability of [14C]FAD to a greater degree than that of [14C]riboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of [14C]riboflavin together with nonradiolabeled FAD. In subsequent studies with mucosal cell extracts, ethanol markedly inhibited activities of FAD pyrophosphatase and flavin mononucleotide (FMN) phosphatase. These findings suggest that dietary sources of riboflavin (FMN and FAD) are not absorbed as well in the presence of ethanol than are vitamin preparations containing riboflavin, which is utilized more readily.

Acetaldehyde↗
PubMed1987

Effects of riboflavin deficiency upon age-related changes in beta-adrenergic and adenosine receptor binding in rat adipocytes.

The binding of (-)(3H)dihydroalprenolol (DHA) and (-)-N6-(3H)phenyl-isopropyladenosine (PIA) to beta-adrenergic and adenosine receptors, respectively, was determined in membranes of adipocytes isolated from riboflavin-deficient rats and age-matched, pair-fed controls for feeding periods of three to forty weeks. In normal chow-fed animals, the binding of both ligands to receptors markedly decreased in older compared to that in younger animals. In young, riboflavin-deficient animals, DHA binding diminished compared to that in age-matched controls. No further decrease in binding of DHA occurred in older, aged-matched, riboflavin-deficient rats. Riboflavin deficiency did not have any effect on PIA binding in either young or old animals. Thus, in riboflavin deficiency, beta-adrenergic binding in adipocyte membranes from young animals is reduced and the normal age-related decrease in this receptor binding does not occur. By contrast, the binding of PIA to adenosine receptors is lower in older than in younger animals regardless of riboflavin nutriture.

Adipose Tissue↗
PubMed1986

New approaches to the possible prevention of side effects of chemotherapy by nutrition.

In an effort to develop new methods for preventing side effects of chemotherapy, the authors initiated studies to determine whether Adriamycin (doxorubicin) inhibits the metabolism of riboflavin (vitamin B2). Adriamycin has been shown to form a 1:1 stoichiometric complex with riboflavin, as well as to compete for binding to tissue proteins. Adult rats treated with Adriamycin in clinically relevant doses were compared to control animals in ability to convert riboflavin into flavin adenine dinucleotide (FAD), the active flavin coenzyme derivative, in heart, skeletal muscle, liver, and kidney. Rats treated with Adriamycin exhibited diminished formation of carbon 14 (14C)FAD in skeletal muscle to nearly 50% that of controls, and in heart to about 70% to 80% of controls. Under these conditions, (14C)FAD formation in liver and kidney was largely unaffected by Adriamycin. In preliminary studies, riboflavin-deficient animals treated with Adriamycin had accelerated mortality rates compared to those of food restricted controls treated with similar doses of Adriamycin. The data as a whole suggest a potential mechanism for Adriamycin-induced cardiac and skeletal myopathy, i.e., inhibition of synthesis of FAD, a flavin coenzyme which is involved in electron transport, lipid metabolism, and energy generation. These findings in an animal model raise the possibility that defects of riboflavin nutriture, either dietary or drug-induced, may be a determinant of Adriamycin toxicity. Further studies are required to explore the potential for preventing side effects due to Adriamycin by administration of this vitamin.

Animals↗
PubMed1985

Inhibition by chlorpromazine of thyroxine modulation of flavin metabolism in liver, cerebrum and cerebellum.

In livers of adult rats that have been treated with thyroxine, the rate of incorporation of radiolabeled riboflavin into both flavin adenine dinucleotide (FAD) and FAD covalently attached to specific apoflavoenzymes was enhanced markedly. By contrast, thyroxine diminished riboflavin incorporation into FAD in cerebrum and cerebellum but continued to enhance incorporation into the covalently bound fraction of FAD. Diminished net incorporation of riboflavin into FAD in brains of adult rats may reflect increased utilization of this fraction for covalent attachment into specific apoflavoenzymes rather than down regulation of the FAD biosynthetic enzymes, flavokinase and FAD pyrophosphorylase, inasmuch as covalent attachment of FAD occurs subsequent to the formation of FAD. The psychotropic drug, chlorpromazine, over a wide dose range, exerted an inhibitory effect on both incorporation of riboflavin into FAD and the utilization of FAD for incorporation into covalently bound flavoenzymes in liver, cerebrum, and cerebellum. Thus, chlorpromazine inhibition of FAD metabolism occurred regardless of the direction of the thyroxine effect and was compatible with an observed inhibitory effect by this drug upon the flavin biosynthetic enzymes.

Animals↗