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Biomedical subjects

A Constantopoulos

Publications and source records attributed to A Constantopoulos.

At least 37 records · Page 2Linked to original sources

Successful response of severe neonatal gram-negative infection to treatment with aztreonam.

Aztreonam was administered to 25 neonates (16 term, 9 premature) with clinically and bacteriologically proved gram-negative infections. Ten patients had meningitis, 9 had septicemia and 6 had urinary tract infections. Patients were between 1 and 28 days of age. Aztreonam was administered intravenously in doses ranging from 40 to 120 mg/kg/day for 10-30 days, depending on the causative organism. All CSF, blood and urine cultures were sterile 48 h after drug treatment had begun. There was no incidence of bacteriologic relapse. Body temperature returned to normal in 96% of patients within 3-4 days of therapy. Aztreonam was well tolerated. One infant experience nausea and vomiting, but no patient was withdrawn from therapy due to adverse reactions.

Aztreonam↗

Effect of ascorbic acid on guinea pig adrenal adenylate cyclase activity and plasma cortisol.

Intra-adrenal ascorbic acid (AsA) concentrations exert a braking or modulating effect upon steroid release. Because changes in steroidogenesis are mediated through alterations in adenylate cyclase activity (ACL), the effect of varied AsA plasma concentrations on guinea pig adrenal ACL activity and plasma cortisol was studied. Forty-two male guinea pigs were randomly allocated to the following seven groups: controls, scorbutic, and groups given 0.1, 5, 10, 20 or 100 mg ascorbic acid/100 g body weight, respectively. Scorbutic animals had very low levels of AsA in comparison to control animals. Plasma AsA levels increased as AsA dose increased. The levels of AsA in the group given 0.1 mg AsA were higher than in controls. Basal adenylate cyclase activity did not vary significantly among animal groups. In contrast, values for NaF-stimulated ACL activity showed a progressive decrease with increasing AsA doses. A highly significant correlation was found between decreasing ACL activity and increasing plasma AsA concentrations. On the other hand, NaF-responsive ACL activity was higher in scorbutic animals than in any other group. Higher mean cortisol values were found in the scorbutic group than in the controls, correlating with high levels of NAF-stimulated ACL activity. Higher mean cortisol values were also found in the group given 0.1 mg AsA although ACL activity in this group was not affected. This finding, coupled with reduced ACL activity in these groups, is consistent with the inhibitory effect of a megadose of AsA on production of cortisol from the adrenal. The above data may suggest that differing plasma concentrations of AsA regulate in vivo steroidogenesis by altering the activity of the membrane-bound enzyme adenylate cyclase.

Adenylyl Cyclases↗

Hepatic uridine-diphosphate glucuronyl transferase activity of guinea pig with scurvy.

Ascorbic acid (AsA) concentrations in plasma exert a modulating effect on the activity of liver enzymes. Since UDP-glucuronyl transferase is a liver enzyme, which is responsible for bilirubin glucuronidation, the effect of varied amounts of AsA on this enzyme activity was studied. Sixty male guinea-pigs were randomly allocated to the following six groups: controls, scorbutic and groups given 2, 5, 10 or 20 mg of ascorbic acid, respectively. All the animals with the vitamin C deficient diet presented clinical signs of scurvy at the end of the experimental period, and had lost both body and liver weight compared to all other groups. Scorbutic animals had very low levels of AsA in the liver compared with controls (0.20 +/- 0.10 and 1.65 +/- 0.45 mg/g liver, respectively) (p less than 0.001). Liver AsA levels increased as the AsA dose increased. The UDP-glucuronyl transferase activity was lower in scorbutic animals than in controls (6.20 +/- 1.95 and 23.85 +/- 4.20 mg bilirubin/g protein/h, respectively) (p less than 0.001). The other groups C, D, E and F also had higher mean levels of UDP-GT activity than the scorbutic group B. Finally, no correlation was found between UDP-glucuronyl transferase activity and ascorbic acid intake.

Animals↗

Augmentation of hepatic uridine-diphosphate glucuronyl transferase activity by antituberculous drugs in hamsters in vivo.

Changes in uridine-diphosphate glucuronyl transferase activity (UDP-GT) in liver homogenates of hamsters treated with different doses of isoniazid (INH), rifampicin (RMP), para-aminosalicylic acid (PAS) and hydrocortisone for several periods of time were studied and expressed as mg of bilirubin conjugated per g of protein per h. INH, RMP, PAS and hydrocortisone induced UDP-GT activity to a statistically significant degree. The optimum dose for high induction was 20 mg for INH, RMP and hydrocortisone, and 200 mg for PAS per kg of body weight. The optimum time of treatment for high induction was 10 consecutive days of intraperitoneal administration for all drugs examined. Such data, particularly for INH and RMP, indicate why patients who receive these drugs show no clinical jaundice, although they develop an hepatitis-like disease with elevation of serum transaminase of hepatic origin. This could be the result of stimulation of the hepatic smooth endoplasmic reticulum which produces rapid conjugation and therefore excretion of bilirubin. Similarly, the antituberculous drugs may cause liver dysfunction by inducing other liver enzymes.

Aminosalicylic Acid↗

Congenital tuftsin deficiency.

The serum tuftsin activity in four different pediatric groups has been studied: (a) 20 premature infants, (b) 20 full-term infants, (c) 20 normal children (controls), and (d) 5 patients with recurrent and severe infections of the respiratory system, skin, and lymph nodes. The normal children as well as the premature and full-term infants had normal tuftsin activity. Tuftsin activity in the serum of the 5 patients in group (d) was absent. Cellular and humoral immunity in these patients was normal. All patients have been shown to have a mutant peptide that is strongly inhibitory to the normal tetrapeptide tuftsin. The clinical response of these patients to gamma-globulin was excellent.

Adolescent↗

Bilirubin-induced modulation of cerebral protein phosphorylation in neonate rabbits in vivo.

Protein phosphorylation in cerebral cell-free preparations from neonate rabbits was inhibited by bilirubin and promoted by aminophylline when these substances had been administered intravenously. In animals given both compounds, the bilirubin-induced inhibition of phosphorylation was partly reversed by aminophylline. Adenosine 3',5'-monophosphate added in vitro during the assays also increased protein phosphorylation. These data introduce new concepts in the pathogenesis of kernicterus.

Aminophylline↗

The effect of glucagon on serum bilirubin levels.

In 20 jaundiced newborn children with mean bilirubin levels of 19.56 mg/100 ml, a single injection of glucagon was given subcutaneously, in a dosage of 80-300 micrograms/kg of body weight. The bilirubin decreased to 17.05 mg/100 ml within 3 h, and this difference was statistically highly significant (p less than or equal to 0.001). In 14 jaundiced newborn patients with mean bilirubin levels of 16.1 mg/100 ml, normal saline instead of glucagon, was injected subcutaneously (controls). The bilirubin value measured 2-3 h later remained almost the same (16.2 mg/100 ml). In 12 jaundiced newborns with mean bilirubin levels of 17.26 mg/100 ml, a single injection of glucagon was given intravenously, in a dosage of 60-100 micrograms/kg of body weight. The bilirubin decreased to 15.30 mg/100 ml within 2-3 h, and this difference was statistically highly significant (p less than or equal to 0.001). Finally, 10 jaundiced newborn children were injected systematically at 8 am and 8 pm with 300 micrograms/kg of zinc-protamine-glucagon continuously for 5 days. All these patients maintained constant bilirubin levels, and none were sent for phototherapy. In all the patients blood glucose levels were increased between 90 and 130 mg/100 ml, 30 min after glucagon injection.

Bilirubin↗

Breast milk jaundice; the role of lipoprotein lipase and the free fatty acids.

Lipoprotein lipase activity and free fatty acid concentrations were measured in samples of milk collected from mothers of infants without and with prolonged neonatal jaundice. The lipoprotein lipase and free fatty acid values in the milk from mothers of infants without jaundice were found to increase with the duration of breast-feeding until the 12th post-partum day, and then to fall to the original levels. In the group of mothers with jaundiced infants both lipoprotein lipase and free fatty acid values were found within normal limits when measured between 15th and 37th days post-partum. These findings indicate that increased values of lipoprotein lipase and free fatty acids in the milk are not responsible for the development of breast-milk jaundice.

Breast Feeding↗

Disseminated neonatal herpes simplex infection treated with levamisole. Report of a case.

Levamisole has been used to treat a patient with disseminated neonatal herpes simplex infection. The skin lesions and the convulsions disappeared completely 20 days after therapy. A trial to reduce the dose of levamisole resulted in a new episode of seizures and skin lesions. A similar relapse was observed at the age of 7 months, which resulted in control of symptoms by increasing the dose of levamisole. The patient has received levamisole for 20 months. She is now 29 months old and is doing well without levamisole, except for a slight motor deficity. If further investigations confirm the present findings, levamisole may well become a useful agent in the treatment of disseminated herpes simplex infection.

Female↗

Serum levels of retinol, retinol-binding protein, carotenoids and triglycerides in children with beta-thalassemia major.

Levels of retinol (vitamin A), carotenoids and triglycerides in the serum of 50 children with homozygous beta-thalassemia have been studied, as well as the ability of the small intestine to absorb a test meal containing retinol palmitate, triglyceride, d-xylose and glucose. On the other hand, 8 patients underwent a dark-adaptation test, and in 40 children with homozygous beta-thalassemia the levels of retinol-binding protein in the serum were estimated. The mean levels of retinol, carotenoids and triglycerides in the serum of the patients were: 23 +/- 4.1 micrograms/dl (controls: 36.3 +/- 4.9), 44 +/- 15.5 micrograms/dl (controls: 103 +/- 24), 117 +/- 20 (controls: 126 +/- 26), respectively. The absorption from the small intestine of retinol, triglycerides, glucose and d-xylose was normal. 6 out of 8 patients studied for visual function showed an abnormal dark-adaptation test, and these 6 children had low serum retinol levels. Finally, the mean serum levels of retinol-binding protein in the patients were 4.74 +/- 0.53 mg/dl (controls: 5.63 +/- 0.58). The low retinol levels were correlated with the low retinol-binding protein values which, in turn, could be due to the abnormal liver function of the patients.

Carotenoids↗

Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3',5'-monophosphate.

The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the regulation of rat liver bilirubin uridine diphosphate glucuronyltransferase (UDP-GT) was studied. Augmentation of UDP-GT activity was obtained by cAMP, but not by 3'-AMP. A single administration of glucagon initiated a rapid but limited increase in enzyme activity, which reached a maximum after 2 hr. Similar augmentation of the hepatic enzyme was produced by injection of N6,O2-dibutyryl cAMP. The nucleotide is the mediator for UDP-GT augmentation by glucagon. The injection of glucagon led within 20 min to a 40-fold increase in the concentration of cAMP. The augmentation of UDP-GT activity by glucagon or dibutyryl cAMP was fully inhibited by actinomycin D. A second stimulation of liver by glucagon or dibutyryl cAMP 4 hr after the first injection, produced a new increase of UDP-GT activity.

Adenosine Monophosphate↗

The effect of levamisole on phosphodiesterase activity.

Phosphodiesterase activity of mouse liver homogenates was estimated in presence and absence of levamisole. The enzyme activity was 1394 and 1399 nmoles/mg protein/30 min respectively. Our data show that levamisole does not affect the phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗