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Biomedical subjects

M Rizzardini

Publications and source records attributed to M Rizzardini.

At least 37 records · Page 2Linked to original sources

[Transient myocardial ischemia in newborn infants].

Thirty new born babies with Apgar scores of 5 or less were randomly selected for clinical and electrocardiographic study. Twenty five had electrocardiographic changes of myocardial ischaemia (ST and T wave abnormalities). Generalised low voltage was a common finding (21 cases) whilst pathological Q waves were observed more rarely (5 cases) but did not seem to carry a poor prognosis. Seventeen babies had cardiac clinical signs: isolated tricuspid regurgitation or associated with cardiac failure. Five babies died; autopsy showed subendocardial infarction in all cases. The electrocardiogram of the survivors returned to normal within 15 days in 80% of cases. The authors discuss the physiopathology and demonstrate a clear relationship between neonatal hypoxia and myocardial ischaemia. Attentive clinical examination and systematic electrocardiography in these babies at risk seem to be justified for the detection and treatment of myocardial ischaemia.

Coronary Disease↗

Porphyrinogenic effect of hexachlorobenzene and 2,3,7,8-tetrachlorodibenzo-para-dioxin: is an inhibitor involved in uroporphyrinogen decarboxylase inactivation?

Uroporphyrinogen decarboxylase from control mouse liver was markedly inhibited in vitro by addition to the incubation mixture of cytosol fractions from livers of porphyric mice. The animals had been subjected to chronic treatment with 2,3,7,8-tetrachlorodibenzo-para-dioxin (25 micrograms/kg per week, intraperitoneally). The cytosol fractions were deproteinized by heating at 100 degrees C for 5 min and freed of porphyrins by treating the supernatants with Zerolit FF (i.p.) resin. Inhibition was proportional to the amount of fraction added and was not observed if the inhibitor fraction was dialysed before incubation. Increasing the substrate concentration did not reverse enzyme inhibition; the Vmax value calculated for the control enzyme in the presence of the inhibitor fraction was decreased, but Km did not vary. Two alternative hypotheses on the nature of the inhibitor compound(s) in the inhibitor fraction are discussed with relation to hexachlorobenzene (HCB) and 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) porphyria.

Animals↗

Cyclophosphamide-impaired regulation of hepatic heme metabolism.

In male rats hepatic cytochromes b5 and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a 'non-cytochromal' form. Parallel to the above changes the heme metabolism showed derangement: delta-aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.

5-Aminolevulinate Synthetase↗

In vitro inhibitory effect on porphyrinogen carboxylyase of liver extracts from TCDD treated mice.

Marked inhibition of porphyrinogen carboxylyase was produced in vitro by cytosol fractions, deproteinized and free of porphyrins, obtained from livers of mice made porphyric by 9 weeks i.p. treatment with 25 micrograms/kg/week of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition was proportional to the amount of the fraction added, was increased by preincubation in the absence of the substrate and, once established, could not be reversed by dialysis. TCDD itself, added to the control enzyme in the incubation mixture, did not affect enzyme activity up to a concentration of 77 nM, which is 10 times higher than the liver TCDD concentration found after in vivo TCDD treatment.

Animals↗

Sex differences in the metabolism of hexachlorobenzene by rats and the development of porphyria in females.

Male and female F 344 rats were dosed every other day for 103 days with 50 mumole of hexachlorobenzene (HCB)/kg. Females developed a hepatic porphyria, the urine and liver levels of porphyrins being 40- and 310-fold higher respectively than those of males. Urine was periodically hydrolysed and analysed for the three metabolites pentachlorophenol, 2,3,5,6-tetrachlorobenzene-1,4-diol and pentachlorothiophenol (derived from the mercapturate). The combined urinary excretion of these was greater in females than males, especially during the first 10 weeks. Pentachlorothiophenol was particularly high in female urine. After 103 days this metabolite was slightly less in female faeces than in male's but free hepatic pentachlorothiophenol was 3.6-fold greater. Although total 24 hr excretions of metabolites were higher by females than males and after 7 daily doses of HCB, a difference in this respect was not conclusively proven. However, total pentachlorothiophenol excretion was always significantly greater by females. The male/female ratios for pentachlorophenol and pentachlorothiophenol in bile were identical to those for faeces. Excretion of metabolites by both adult males and females was stimulated by pretreatment with diethylstilboestrol (DES). No sex differences in metabolism were observed with immature rats.

Animals↗

Induction of mixed-function oxidase by chronic treatment with 2,3,7,8-tetrachloro-dibenzo-p-dioxin in female rats.

The effect of a 45-week treatment with different doses of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) (0.01, 0.10 and 1.00 microgram/kg/week) was evaluated in female rat liver by determining cytochrome P-450 and b5 content and the activities of the enzymes cytochrome c reductase, aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-ECD); TCDD content in the liver was also measured. Cytochrome b5 and cytochrome c reductase were unaffected at any of the dose levels and cytochrome P-450 was significantly induced only at the highest TCDD dose, but marked induction of AHH and 7-ECD was apparent when the animals were treated with 0.01 microgram/kg/week; a clear dose-response relationship was present in the induction at the 2 lower doses (0.01 and 0.10 microgram/kg/week). The amount of TCDD found in liver tissue (1050, 4740 and 30 700 ppt, respectively, for 0.01, 0.10 an 1.00 microgram/kg/week) indicated a relatively higher accumulation of this compound at lower doses.

Animals↗

Effects of chronic treatment with di-(2-ethylhexyl) phthalate on rat liver microsomal activities.

The effects of chronic di-(2-ethylhexyl)phthalate (DEHP) on liver microsomal activity were studied in rats. Daily doses of 50 and 500 mg/kg for 4 weeks did not affect O-demethylation, aromatic hydroxylation, N-demethylation, C3-hydroxylation, styrene monooxygenase, glutamic-oxalacetic and glutamic-pyruvic transaminases (GOT, GPT). Inhibition of glutathione-S-transferase A and C and induction of epoxide hydrase, glutathione-S-transferase B and nitroreductase activity were instead observed. Protein, cytochrome P-450 and reduced glutathione levels in liver did not appear to be affected by DEHP pretreatment.

Animals↗

Quantitative thin-layer chromatographic measurement of n-trifluoroacetyladriamycin-14-valerate (AD 32) and trifluoroacetyladriamycin (AD 41) in blood and tissues.

A thin-layer chromatographic method has been developed for the detection and measurement of N-trifluoroacetyladriamycin-14-valerate (AD 32) and its major metabolite trifluoroacetyladriamycin (AD 41). The procedure gives satisfactory linearity over a large range of concentrations. The coefficient of variability is about 10% over the entire range of usable concentrations, giving good reproducibility; sensitivity is 25 ng for both AD 32 and AD 41. Analysis is specific for AD 32 and AD 41 since adriamycin or more polar metabolites can be differentiated. Recovery is high (85-90%) and the method is simple and economical to use. Pharmacokinetics of AD 32 and AD 41 are reported in blood and some tissues of mice bearing Lewis Lung carcinoma.

Animals↗

Effects of phlebotomy on urinary porphyrin pattern and liver histology in patients with porphyria cutanea tarda.

Urinary porphyrin profiles and liver histology have been investigated in a group of adult alcoholics with porphyria cutanea tarda (PCT) before and after one year phlebotomy. Both parameters were evaluated during the same period in a group of patients who did not undergo specific therapy for PCT. All patients were advised to abstain from alcohol. At the end of the one year observation period there was a significant fall of urinary total porphyrins and in the uro/coproporphyrin ratio in treated patients compared to basal values whereas no changes were found in controls. Liver biopsy findings revealed a significant reduction of hepatic fatty degeneration and siderosis with no changes in inflammatory infiltrates and fibrosis in treated patients, so the progression of liver disease was similar to controls. These results show that clinical and biochemical remission of PCT can occur independently of the evolution of the concomitant liver disease.

Alcoholism↗

[Postnatal growth of very low birth weight newborn (LBW infant). Anthropometry after a period of 3 years, longitudinal study].

Growth of 230 very low birth weight infants (VLBWI) admitted to the neonatal wards of a metropolitan pediatric hospital at Santiago, Chile was studied prospectively up to 36 months of age, in the period 1980-1988. For further analysis patients were separated in groups A, 60 newborn infants with birth-weight below 1,001 g and B, 170 newborn infants with birth-weight between 1,001 and 1,500 g. We used Patri's growth charts, to compare the results with full term healthy newborns of 3,318 g average birth-weight from the same socio-economical status. The average weight of group A infants was below 2 SD at age one year and between one and two SD at 2 and 3 years of age. In group B infants weight was between one and 2 SD at one year of age and below 1 SD at 2 years. At age 3 years average weight was very close to normal. Group A infants were not successful to achieve the average height of the standard at age 3 year, but this same goal was obtained at 2 years of age in group B infants. Head circumference was within the normal average at ages 3 and 2 year in group A and B infants, respectively.

Anthropometry↗

[Parenteral nutrition in critically ill newborns].

In nine critically ill newborns, five of them with intractable diarrhea and four surgical patients, we administered a 5% crystalline aminoacids solution (AA) and glucose in sufficient amount to provide 120 cal times kg. in 24 hours. Six of them recovered after receiving parenteral alimentation for 3 to 15 days, gained weight during or after treatment and were discharged from the hospital in good conditions. Three died, one of them presented septicemia and two pneumonia and pulmonary infarcts. The solution used generated few metabolic alterations, the acid-base status remained within normal range and there were not important changes in the sodium and potassium serum concentrations. On the contrary, children with hyponatremia and hypokalemia at the beginning of the treatment, normalized these constants within the first hours, as diarrhea ceased. The most frequent complications were infiltrations and reaction of the surrounding tissue of the catheterized vein and local skin infection. Only one patient died of septicemia, possibly caused by this proceeding. In summary, parenteral alimentation though not free from risk, seems to be a useful proceeding when oral feeding is impossible or inadvisable. The utmost danger is septicemia. Metabolic changes are minimal and they do not mean a risk for child's life; nevertheless, there is a need for long term studies to bring up definite conclusions. The solutions in actual use are probably not the most physiological for the newborn. It is necessary to adequate them according to the new advances made on child nourishment during his first days of life.

Acute Disease↗

[Height, weight and head circumference according to gestational age in newborn infants born before 35 weeks].

A retrospective and collaborative study was done in Santiago, Chile, in order to obtain national data on birth-weight, height and head circumference of babies born at 24 to 34 weeks of gestation: 370 babies with reliable gestational age, single pregnancies and no maternal nor fetal morbidity were included in the study. Babies were born in three government and one private hospitals from 1982 to 1987. Mean birthweight, height and head circumference for each gestational age from 24 to 34 weeks are presented in tables with their S.D. and charts +/- 1.5 S.D. The national use of these tables and curves is recommended.

Birth Weight↗

[Postnatal growth of very low birth weight infants. II. Anthropometry at one year of age, a longitudinal study].

A prospective study up to one year of age, was done in 154 newborns with birth weight less than 1,501 g at a Metropolitan Hospital of Santiago, Chile, between 1983 and 1987. The patients were divided in groups A: 44 patients with birth weight less than 1,001 g; B: 68 patients with birth weights from 1,000 to 1,250 g and C: 48 patients with birth weight 1,251 to 1,500 g. At age one year weight of group A patients was 6,724 +/- 804 g; group B 7,782 +/- 927 g and group C 7,941 +/- 903 g. Weight and height of group A babies at one year of age were below 2 DS of the average weight and height for normal chilean babies of the same socioeconomic status and geographic area with 3,318 g mean birth weight. Group B and C were between 1 and 2 DS. Head circumference was within normal ranges in groups B and C patients, but in group A patients if was below 2 DS of the average.

Body Height↗