Bruno Granati

Distribution of endogenous and injected porphyrins at the subcellular level in rat hepatocytes and in ascites hepatoma.

Different doses (0.5-20 mg/kg) of hematoporphyrin (HP) have been injected intraperitoneally into normal rats and rats affected by Yoshida ascites hepatoma. About 80% of HP reaching the liver was recovered in the extracellular compartment after liver perfusion, the ratio of extra- to intracellular HP being essentially independent of the administered dose. Similar data were obtained at different times after injection of 20 mg/kg HP. Intracellular HP largely accumulates in the mitochondria and in the membrane components of the nuclear fraction of isolated hepatocytes. Kinetic studies suggest that the cell receptors of highest affinity for HP are present in the external membrane. The latter result obtains for ascites hepatoma cells in an even more evident way, although the latter cells exhibit secondary HP binding sites probably constituted by cytoplasmatic proteins. Moreover, the clearance of intracellular HP from malignant cells occurs at a remarkably lower rate as compared with HP clearance from liver cells.

Inhibitory Effects of Bilirubin and Photobilirubin on Neonatal and Adult T Lymphocytes and Granulocytes

The lymphoproliferative response to phytohemagglutinin of lymphocytes and spontaneous motility, chemotaxis and phagocytic activity of granulocytes were studied in the newborn and adult blood in the presence of bilirubin and photobilirubin. All of these activities were inhibited to the same extent by these substances. In addition, a significant difference between newborn and adult values was found. In conclusion, the authors suggest that phototherapy does not decrease bilirubin cellular toxicity.

Evaluation in Guinea Pigs of the Allergenic Capacity of Two Infant Formulae Based on Hydrolyzed Milk Proteins

The purpose of the present study was to evaluate the potential capacity of infant formulae based, respectively, on hydrolyzed casein and on hydrolyzed whey proteins to induce sensitization in guinea pigs. This potential capacity was tested by intravenous challenges with centrifuged formulae and by passive cutaneous anaphylaxis. The results showed that neither formula was sensitizing, therefore suggesting that protein hydrolyzates can be considered a suitable cows milk substitute for infants with cows milk protein intolerance. However, further studies are necessary in order to investigate whether these hydrolyzates are not allergenic in infants as well.

Sites of Action of Light during Phototherapy

In order to investigate the main sites of action of phototherapy in the treatment of neonatal jaundice we studied (a) the in vivo and in vitro relationship between the hematocrit and the effectiveness of phototherapy, and (b) the effect of varying the skin area exposed to light. The results show that the hematocrit does not influence in vivo the efficacy of phototherapy, while they confirm that the total skin surface exposed to light is important in determining the effectiveness of light treatment. The authors have also studied the possible action of phototherapy on bilirubin solutions placed into the postmortem brain or the stomach. The results suggest that blue light does not penetrate strongly enough to photomodify the exposed pigment.

Molecular and Cellular Mechanisms in Photomedicine: Porphyrins in Cancer Treatment

The use of visible light in combination with a photosensitizing dye for the treatment of various types of tumors has been repeatedly attempted since the early 1900s when topically applied eosin and sunlight were shown to induce the regression of skin tumors1. This approach appears to be particularly attractive since i) several photosensitizers with a polycyclic chemical structure, including xanthenes2, acridines3, and psoralens4, display a preferential affinity for neoplastic as compared with normal cells; and ii) most cell constituents, in particular proteins and nucleic acids, are insensitive to the direct action of visible light. In principle, these two properties should allow one to restrict the photodynamic effects causing cell inactivation and necrosis to the dye-loaded tissue, with no concomitant damage to normal dye-free tissues, provided a suitable set of light wavelengths is selected for irradiation. Thus, photodynamic therapy exhibits a potential advantage with respect to other therapeutic modalities for tumors which are based on the use of ionizing radiations; in the latter cases, the simultaneous irreversible damage of normal tissues often limits the extent and efficacy of the treatment. Toward this aim, an ideal photosensitizer should have the following properties: i) lack of systemic toxicity; ii) selective uptake and retention by malignant tissues; iii) selective absorption of the incident light; and iv) efficient generation of photoreactive species leading to destruction of malignant tissues.

THE PREVENTION OF RESPIRATORY DISTRESS SYNDROME IN PREMATURE INFANTS: EFFICACY OF ANTENATAL AMINOPHYLLINE TREATMENT VERSUS PRENATAL GLUCOCORTICOID ADMINISTRATION

Antepartum administration of Aminophylline (AF) to pregnant animals resulted in accelerated and increased pulmonary maturation as well as in decreased morbility and mortality from RDS in premature offspring. The present study was undertaken to evaluate the effect of antenatal AF treatment on the frequency of RDS among premature infants born of women who were treated (18) and to compare this group with a bethamethasone (GC) treated group (16 women) and with a control (C) one (40 women). Statistical significant differences were noted between the AF and GC groups and the C group in the incidence of RDS (AF=11%; GC=0%; C=45%) and in the frequency of perinatal deaths (AF and GC=0%; C=25%). Furthermore a significant difference was noted between the AF group and the GC and C groups in the incidence of neonatal signs of infection (AF=0%; GC=50%; C=37.5%). The authors conclude that antenatal AF treatment may be as effective as GC in the prevention of RDS in premature infants with, for the moment, no side effects.

11 ANTENATAL AMINOPHYLLINE ADMINISTRATION

Antenatal administration of glucocorticoids (GC) seems to decrease the incidence of RDS by means of various mechanisms including surfactant production. Aminophylline (AF) has also been proposed for the prevention of RDS. We have evaluated the effect of antenatal AF treatment (2, 5 mg/kg/hr for 3 days) on the frequency of RDS in 30 preterm newborns ≤32 weeks of gestational age and compared this treatment with the GC administration (betametasone 4 mg i.m. every 8 hrs for 48 hrs) given to 18 mothers delivering premature newborns ( ≤32 weeks g.a.). Thirty-two premature newborns (≤32 weeks g.a.) born to mothers not receiving drugs served as controls. In this series, AF was able to significantly reduce the incidence of RDS type II (Fisher test=0.03), but not the incidence of RDS type I (Fisher test = 0.07). The mortality rate was 4 out of 30. On the contrary GC did not significantly reduce either RDS type I or type II (Fisher test=0.5 and 0.25). In this group 5 out of 18 premature newborns did not survive. In the control group the survival rate was 23 out of 32. AF did appear to be well tolerated by the mother and seems to act on the fetus stimulating the respiratory center and possibly decreasing the fluid filtration across the alveolar-capillary barrier, reducing RDS type II.

NEONATAL OUTCOME IN TWO DIFFERENT TRIALS OF ANTIHYPERTENS ANTIHYPERTENSIVE TREATMENT IN PREGNANCY

Severe hypertension in pregnancy (resting diastolic blood pressure ⩾ 110 mmHg ε proteinuria) is a threat to the wellbeing of the mother and her newborn infant. However, very few studies have assessed the value of antihypertensive drugs on the fetal outcome. We report data from 65 infants born to hypertensive mothers treated with clonidine and diuretics (group 1) and from 97 babies born to mothers treated with captopril and labetalol (group 2). The findings of group 1 were compared to those of group 2 and both were then compared to those obtained from gestational age-matched infants born to normotensive mothers (group 3 n.162). The results are presented in the following table:This study confirms that severe hypertension in a pregnant woman is a disease shared even by her fetus. Furthermore, we have shown that even the use of very recent drugs, such as captopril and labetalol,do not result in any advantage for the neonatal outcome.

NETILMICIN IN PREMATURE AND FULL-TERM INFANTS: ITS EFFECTS ON THE RENAL AND AUDITORY FUNCTIONS AND ITS KINETICS ACCORDING TO MULTICOMPARTMENT MODEL

68 neonates with gestational age ranging from 27 to 40 weeks, 6-15 days postnatal age and 800-3400 g birth weight were treated for 5-14 days with Netilmicin (N), 2.5 mg/kg/b.i.d. or t.i.d. according to postconceptional age. Their renal function was studied by measuring serum creatinine concentrations during and up to 15 days after therapy. The urinary excretion of N-acetyl-glucosaminidase (NAG) was measured as a marker of tubular injury. Valley N serum levels were monitored during the treatment. Serum and urinary washout profile of the drug were followed for up to 10-15 days after discontinuation. Behavioral and impedance audiometry are being performed between 6 to 12 months of age. Treatment with N (always in association with a β-lactam antibiotic) did not represent for the newborns a source of toxicity as far as either renal or auditory (38 infants so far examined) function are concerned. Small preterm neonates (≤34 weeks G.A.) more frequently had elevated valley serum N concentration (≥3 ug/ml). The serum and urinary washout followed a multiexponential decay with prolonged terminal T 1/2 indicating tissue accumulation.