Search PubMed⌕ Search

Biomedical subjects

A Kappas

Publications and source records attributed to A Kappas.

At least 19 recordsLinked to original sources
PubMed2000

Molecular aspects of the inherited porphyrias.

The porphyrias are diseases due to marked deficiencies of enzymes of the haem biosynthetic pathway (Fig. 1). Except for the first enzyme of the pathway, delta-aminolevulinate synthase (ALAS), deficiencies in seven other enzymes are associated with the various forms of porphyria (Fig. 2). Porphyrias can be classified as either hepatic or erythroid, depending on the major site of production of porphyrins or their precursors. The pathogenesis of all inherited porphyrias has now been defined at the molecular level, and it is clear that there is a great deal of genetic heterogeneity in each porphyria [1].

Erythrocytes↗
PubMed1999

Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit. PURPOSE: To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV. PATIENTS AND METHODS: From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m2/week x 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m2/week x 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m2) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients). RESULTS: As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%. P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001). CONCLUSIONS: The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.

Adult↗
PubMed1999

Negative regulation of human heme oxygenase in microvessel endothelial cells by dexamethasone.

Heme oxygenase-1 (HO-1) is a stress protein, and its induction has been suggested to participate in defense mechanisms against agents that promote oxidative injury such as endotoxins and heme. We have shown that the inflammatory cytokines, interleukin-6 (IL-6) and heme-induced HO-1 gene expression, were suppressed by dexamethasone (Dex) in a sustained manner. We examined the mechanism by which the anti-inflammatory agent, Dex, inhibits IL-6 and heme-induced HO-1 expression in rabbit coronary endothelial cells. Endothelial cells treated with heme (10 microM) and IL-6 (25 ng/ml), increased HO-1 mRNA 15- and 60-fold, respectively. The activity of HO was increased 3-fold after such treatment. Although Dex failed to inhibit heme-mediated HO-1 mRNA and HO activity, it was able to reverse IL-6-stimulated HO activity. Several human HO-1 promoter-drive chloramphenicol acetyltransferase (CAT) constructs were examined to analyze IL-6 and Dex-mediated modulation of the HO-1 gene in endothelial cells. CAT assays revealed that the HO-1 promoter region between -180 and -1500 might contain a Dex-mediated negative regulator. Gel mobility shift assays using nuclear extracts from IL-6-treated endothelial cells showed a binding to the synthetic 21 base pairs of the HO-1 sequence that contains the putative STAT3 sequence. STAT3-specific probe inhibited nuclear binding protein to the putative HO-1-STAT3 sequence. This suggests that IL-6 induction of human HO-1 is mediated via the JAK-STAT pathway and that Dex inhibition of gene expression is carried out by activation of a transcriptional protein in competition with the STAT3 binding site.

Acute-Phase Proteins↗
PubMed1999

Comparative pharmacology of zinc mesoporphyrin and tin mesoporphyrin: toxic actions of zinc mesoporphyrin on hematopoiesis and progenitor cell mobilization.

The effects of two synthetic heme analogues, zinc mesoporphyrin (ZnMP) and tin mesoporphyrin (SnMP), on in vivo hematopoietic progenitor cell mobilization and in vitro hematopoiesis were examined in rabbit bone marrow. Rabbits received granulocyte colony-stimulating factor (rhG-CSF) for 7 days in order to mobilize increased numbers of erythroid (BFU-E) and myeloid (CFU-GM) progenitors in peripheral blood. Concurrent treatment of rhG-CSF-treated rabbits with ZnMP reduced mobilization of the numbers of BFU-E (76% inhibition, p < 0.0001) and CFU-GM (70% inhibition, p < 0.005) in peripheral blood. In contrast, SnMP administered at the same concentration had no significant suppressive effect on BFU-E and CFU-GM recruitment. Both metalloporphyrins inhibited bone marrow heme oxygenase activity equally in vivo, thus indicating that both compounds enter bone marrow cells. Direct in vitro addition of ZnMP to normal rabbit bone marrow cultures suppressed BFU-E and CFU-GM growth, whereas SnMP had no such effect. These results confirm, in an in vivo system, our earlier in vitro studies and demonstrate that, at the concentrations studied, ZnMP, in contrast to SnMP, displays toxicity for hematopoietic growth and progenitor cell production.

Animals↗
PubMed1999

Pharmacologic effects of the red blood cell substitutes cross-linked and non-cross-linked hemoglobins on hematopoiesis in rabbits.

The red blood cell substitutes beta-beta cross-linked (DECA-Hb, XLBV-Hb) and non-cross-linked (HbA) hemoglobins (Hbs), were transfused into rabbits and their effects on hematopoiesis examined. All rabbits receiving DECA-Hb or XLBV-Hb tolerated the Hbs well, whereas 50% of the animals transfused with similar doses of non-cross-linked HbA died. Analysis of peripheral blood and bone marrow BFU-E and CFU-GM production revealed that there was no significant variation in the generation of BFU-E and CFU-GM numbers for each cross-linked Hb transfusion group, but there were significant reductions in the HbA group. In animals transfused with cross-linked Hbs, splenic heme oxygenase (HO) activity was similar to that of controls; liver HO activity was slightly elevated, whereas HO activity was significantly increased in kidneys. Transfusion with non-cross-linked HbA produced greater inductions of HO activity in the liver and kidneys. Hepatic delta-aminolevulinic acid synthase (ALAS) activity was significantly reduced in HbA-transfused animals, whereas transfusion with cross-linked Hbs produced only minor, statistically nonsignificant, reductions in ALAS activity.

5-Aminolevulinate Synthetase↗
PubMed1999

Heme oxygenase inhibitors transiently increase serum ferritin concentrations without altering other acute-phase reactants in man.

Sn protoporphyrin (SnPP) and Sn mesoporphyrin (SnMP), potent inhibitors of heme oxygenase (HO), significantly suppress bilirubin production, lower serum and biliary bilirubin levels and increase biliary heme output in animals and man. In this study, 20 healthy volunteers, 7 patients with primary biliary cirrhosis and 4 patients with idiopathic hemochromatosis were treated with SnPP and 4 healthy volunteers with SnMP. In all cases, serum ferritin levels increased substantially but transiently after administration of these HO inhibitors. Values returned to baseline within a few days. Infusion of hematin in 4 healthy volunteers did not significantly affect ferritin levels. No increases occurred in 7 other acute-phase reactants. The observation that these HO inhibitors transiently increase serum ferritin levels implies a link between ferritin, iron metabolism and HO activity which may be usefully explored in disorders of iron metabolism.

Acute-Phase Proteins↗
PubMed1999

Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of bilirubin production Sn-mesoporphyrin.

OBJECTIVE: To assess the efficacy of Sn-mesoporphyrin (SnMP), a potent inhibitor of bilirubin production, in: a) moderating the need for phototherapy (PT) in full-term breastfed infants with plasma bilirubin concentrations (PBC) of >/=256.5 micromol/L and </=307.8 micromol/L (>/=15 mg/dL and </=18 mg/dL, respectively) that were reached between >/=48 and </=96 hours of age; b) diminishing the time required for the PBC to decline to </=222.3 micromol/L (</=13 mg/dL) (closure of the case); c) decreasing the number of bilirubin determinations required for monitoring hyperbilirubinemia. STUDY PARTICIPANTS: Healthy full-term breastfed infants with a PBC between >/=256.5 micromol/L and </=307.8 micromol/L (>/=15 mg/dL and </=18 mg/dL, respectively) reached between 48 to 96 hours of age. DESIGN/METHODS: After obtaining informed consent from the parents, infants were randomized to either the SnMP (6.0 micromol/kg birth weight, single dose, intramuscular) group or the control group. The infants' PBCs were followed by daily measurements either in the hospital or at discharge as outpatients until the hyperbilirubinemia had subsided (PBC </=222.3 micromol/L [13mg/dL]). The total number of newborns enrolled in the study was 84; the SnMP group comprised 40 infants; the control group comprised 44 infants. The groups were similar in sex ratio, birth weight, gestational age, PBC, and age at enrollment. All infants were breastfed. Phototherapy was initiated at a PBC of 333.5 micromol/dL (19.5 mg/dL). RESULTS: SnMP entirely eliminated the need for supplemental PT to control hyperbilirubinemia; in contrast, of the 44 control infants, 12 required treatment with PT (27%) when their PBC reached or exceeded the level (333.5 micromol/dL; 19.5 mg/dL) at which time the use of PT was dictated by hospital guidelines. None of the 40 SnMP-treated infants reached a PBC of 19.5 mg/dL. SnMP also markedly diminished the median hours to case closure (SnMP: median, 86.5 hours; minimum/maximum, 24/216 hours; controls: median, 120 hours; minimum/maximum, 72/336 hours); and significantly reduced the number of bilirubin determinations required for clinical monitoring of the infants (SnMP: median, 3; minimum/maximum, 1/9; controls: median, 5; minimum/maximum, 3/11). No adverse effects of SnMP use were observed. CONCLUSION: A single dose of SnMP proved effective in controlling severe hyperbilirubinemia in full-term breastfed newborns with high bilirubin levels between 48 and 96 hours. In addition, SnMP eliminated the need for PT and reduced the use of medical resources in the clinical treatment of this problem as well as the related, important and painful, emotional costs for both mothers and infants.

Bilirubin↗
PubMed1999

Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression.

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme; the latter generates pro-oxidant products, including free radicals. Two HO isozymes, the products of distinct genes, have been described; HO-1 is the inducible isoform, whereas HO-2 is suggested to be constitutively expressed. We studied the inducing effect of several metal compounds (CoCl(2), stannic mesoporphyrin, and heme) on HO activity. Additionally, we studied HO-1 expression in experimental models of adhesion molecule expression produced by heme in endothelial cells, and the relationship of HO-1 expression to the induced adhesion molecules. Flow cytometry analysis showed that heme induces intracellular adhesion molecule 1 (ICAM-1) expression in a concentration (10-100 microM)- and time (1-24 h)-dependent fashion in human umbilical vein endothelial cells. Pretreatment with stannic mesoporphyrin, an inhibitor of HO activity, caused a 2-fold increase in heme-induced ICAM-1 expression. In contrast, HO induction by CoCl(2) decreased heme-induced ICAM-1 expression by 33%. To examine the contribution of HO-1 and HO-2 to endothelial HO activity, specific antisense oligonucleotides (ODNs) of each isoform were tested for their specificity to inhibit HO activity in cells exposed to heme. Endothelial cells exposed to heme elicited increased HO activity, which was prevented (70%) by HO-1 antisense ODNs. HO-2 antisense ODN inhibited heme-induced HO activity by 21%. Addition of HO-1 antisense ODNs prevented heme degradation and resulted in elevation of microsomal heme. Western blot analysis showed that HO-1 antisense ODNs selectively inhibited HO-1 protein and failed to inhibit HO-2 protein. Incubation of endothelial cells with HO-1 antisense enhanced heme-dependent increase of ICAM-1. In contrast, addition of HO-2 antisense to endothelial cells failed to increase adhesion molecules. The role of glutathione, an important antioxidant, was examined on heme-induced ICAM-1 expression. Endothelial cells pretreated with a glutathione precursor, N-acetylcysteine, or glutathione ester, showed a decrease in heme-induced ICAM-1 expression of 37 and 44%, respectively, suggesting that the mechanism of ICAM-1 induction by heme may be partly dependent on the levels of antioxidant. It is possible that amelioration of the heme-induced oxidative stress and expression of ICAM-I is due, in part, to the induction of HO-1 activity. Regulation of HO activity in this manner may have clinical applications.

Cells, Cultured↗
PubMed1999

Induction of micronuclei in human lymphocytes by organic solvents in vitro.

Our work is focused on identifying micronuclei (MN) induced in whole blood lymphocyte cultures after treatment with the organic solvents toluene, benzene, and acetone. We used the micronucleus test as a cytogenetic biomarker for genotoxicity and treated whole blood cultures with different concentrations of these solvents (0.1 to 5 mM) and mixtures of them (toluene plus acetone, toluene plus benzene). Our results did not show a significant increase in the number of micronuclei in binucleated lymphocytes after 48 hr of in vitro treatment. The addition of an external metabolic factor (10% S9 mix for 2 hr) in blood cultures treated with the organic solvents or their mixtures did not cause induction of MN. These results indicate the lack of genotoxic activity of toluene, benzene, and acetone in vitro.

Acetone↗
PubMed1998

Specific recombinogenic activity of a new polyene antibiotic.

A new antibiotic from Streptomyces sp., tetrapol A159, active against various fungi, a promising compound for the control of plant diseases, was studied for its genotoxic effects. It was produced at the Institute of Microbiological Preparations for Agriculture, Sofia, Bulgaria. The chemical was tested in three different test systems: a bacterial system, the Ames test for point mutations, the micronucleus test in bone marrow cells of rats for chromosomal aberrations and the fungal system of Aspergillus nidulans for mitotic recombination and aneuploidy. No increase in histidine revertants was observed in any of the TA100, TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to 4000 mg/plate. The results were also negative in the micronucleus test of bone marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a statistically significant threefold increase of mitotic crossovers was found in Aspergillus, at concentrations from 0.5 to 2.5 mg/ml.

Animals↗
PubMed1998

Sn-mesoporphyrin suppression of hyperbilirubinemia in EHBR/Eis rats, an animal model of Dubin-Johnson syndrome.

Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase (HO), controlled hyperbilirubinemia in rats of the mutant strain EHBR/Eis. This mutant strain displays pronounced conjugated hyperbilirubinuria and dark pigmentation of hepatocytes, characteristics of the Dubin-Johnson syndrome. SnMP administered at a dose of 10 mumol/kg body weight produced an immediate decrease in plasma bilirubin concentrations which could be maintained by weekly injections of this synthetic heme analogue. Marked inhibition of HO activity was demonstrated in liver, kidney and spleen but not in brain. These results demonstrate that SnMP can lower plasma bilirubin concentrations for extended periods in a new mutant rat model of Dubin-Johnson syndrome.

Animals↗
PubMed1998

Control of hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns using an inhibitor of bilirubin production, Sn-mesoporphyrin.

BACKGROUND: Hyperbilirubinemia in new-borns with glucose-6-phosphate dehydrogenase (G6PD) deficiency is a serious clinical problem because of the severity and unpredictability of its course. An innovative approach to this problem is suggested by previous experience with Sn-mesoporphyrin (SnMP), a potent inhibitor of bilirubin production, in moderating neonatal hyperbilirubinemia caused by ABO incompatibility, immaturity, and unspecified mechanisms. OBJECTIVE: To compare the effectiveness of the preventive and therapeutic uses of SnMP in ameliorating the course of bilirubinemia of G6PD-deficient neonates. METHODS: Neonates born at the Metera Maternity Hospital, Athens, Greece, and found to be G6PD-deficient by cord blood testing were stratified by sex and gestational age (210-265 days and >265 days) and randomized in pairs to receive SnMP (6 micromol/kg birth weight, intramuscularly) either on the first day of life (preventive use) or if and when the plasma bilirubin concentration (PBC) level reached an age-specific threshold level for intervention (therapeutic use). In the case of failure of SnMP to control the rise of PBC levels, the protocol defined precisely the threshold PBC levels for switchover to phototherapy (PT) and, if necessary, exchange transfusion. PBC was measured daily until a declining value was obtained and the case was closed. RESULTS: A total of 86 G6PD-deficient neonates were randomized: 42 in the preventive arm and 44 in the therapeutic arm. Of the latter, 20 (45%) reached PBC levels requiring therapeutic intervention and thus received SnMP. Regardless of the trial arm, none of the 86 neonates required PT, whereas in a previous study in the same population, 33% of G6PD-deficient neonates required PT. In the intrapair sequential analysis, the favored arm was decided on the criterion of the age at closure of the case being shorter by at least 1 day. After plotting 30 untied pairs in the sequential analysis graph, the preventive use of SnMP proved to be the favored arm, and the trial was stopped. At this point, there were 2 unpaired neonates, 12 tied pairs, 22 pairs in which the preventive use of SnMP was favored and 8 pairs in which the therapeutic use of SnMP was favored. In the group analysis, infants in the preventive group, compared with those in the therapeutic group, had a lower maximum PBC level (8.2 +/- 3.1 and 10.9 +/- 2.8 mg/dL, respectively), which was reached at an earlier age (63.5 +/- 34.8 and 82.2 +/- 24.7 hours, respectively) as well as a lower closing PBC level (7.2 +/- 2.9 and 9.6 +/- 2.5 mg/dL, respectively) and an earlier age at closing (89.1 +/- 35.6 and 110.8 +/- 23.6 hours, respectively). Moreover, a PBC level of >/=8.0 mg/dL, a level at which jaundice is clearly visible, was not reached by 52% of the neonates in the preventive arm and 16% of the neonates in the therapeutic arm. CONCLUSIONS: In G6PD-deficient neonates, a single dose of SnMP administered preventively or therapeutically entirely supplanted the need for PT to control hyperbilirubinemia. The preventive use of SnMP offers practical advantages in populations with a high enough prevalence of G6PD deficiency to justify cord blood screening.

Bilirubin↗
PubMed1997

Heme oxygenase induction with attenuation of experimentally induced corneal inflammation.

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular levels of heme and hemeproteins; certain of the latter, i.e. cytochrome P450s, generate pro-inflammatory products from endogenous substrates. Two HO isozymes, the products of distinct genes, have been described; HO-1 is the inducible one, whereas HO-2 is believed to be constitutively expressed. We studied the inducing effects of several metal compounds [CoCl2, SnCl2, ZnCl2, heme, and cobalt protoporphyrin (CoPP)] on HO-1 mRNA content and enzyme activity in cultures of rabbit corneal epithelial (RCE) cells; these metal compounds are known to induce HO in other tissues. Additionally, we studied HO-1 expression in an experimental model of ocular inflammation produced in rabbit corneas by extended contact lens wear, and the relation of HO expression to the induced inflammatory process. SnCl2 added to RCE cells in vitro produced marked time- and concentration-dependent increases in HO-1 mRNA and HO-1 enzyme activity; CoCl2, ZnCl2, and CoPP were inducers of HO as well, though to a lesser degree than SnCl2. Corneas treated for 6 days with contact lenses impregnated with SnCl2 displayed substantially less corneal inflammation, swelling, and new vessel invasion than did controls; attenuation of ocular inflammation was paralleled by SnCl2-induced increases in HO mRNA and HO activity in corneal epithelial cells from treated eyes. It is suggested that amelioration of the inflammatory response produced by extended contact lens wear is due, in part, to the induction of high levels of HO-1 activity by SnCl2, which results in diminished production of pro-inflammatory mediators generated through heme-dependent metabolic processes. Regulation of HO activity in this manner may have clinical applications.

Animals↗
PubMed1997

Zinc porphyrins: potent inhibitors of hematopoieses in animal and human bone marrow.

The effects of selected heme analogues on heme oxygenase activity in tissues and on human and rabbit bone marrow hematopoietic colony growth were examined. Zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP), at concentrations ranging between 1 and 20 microM, produced significant inhibition of human and rabbit bone marrow erythroid (CFU-E, BFU-E) and myeloid (CFU-GM) colony growth. The growth inhibition produced by ZnPP or ZnMP was not overcome with exposure of cultures to elevated levels of the growth factors erythropoietin and granulocyte-macrophage colony stimulating factor. In contrast, tin protoporphyrin and tin mesoporphyrin did not display any significant bone marrow toxicity when used at similar concentrations. In other studies, differential effects of tin mesoporphyrin and ZnMP administered intravenously on kidney heme oxygenase were demonstrated. Chromium mesoporphyrin administered intravenously proved lethal to animals. These results indicate that exposure of bone marrow to ZnPP and ZnMP can be deleterious to hematopoietic cells and raise the possibility that ZnPP, which is endogenously formed and found in high concentration in red blood cells in lead-poisoned children, may itself participate in the bone marrow toxicity produced by this metal.

Animals↗
PubMed1997

The effect of environmental aneuploidy-inducing agents on the microtubule architecture of mitotic meristematic root cells in Hordeum vulgare.

Microtubules are the prime components involved in chromosomal segregation, their functional accuracy ensuring maintenance of the normal karyotype in the progeny. Chemically-induced disruption of microtubules during mitosis can lead to aneuploidy. In this study, seven environmental chemicals, i.e. cadmium chloride (CD), econazole nitrate (EZ), benomyl (BM), thiabendazole (TB), griseofulvin (GF), thimerosal (TM) and hydroquinone (HQ), were tested for their ability to induce microtubule disruption in mitotic meristematic root cells of the higher plant Hordeum vulgare, with the use of anti-tubulin indirect immunofluorescence microscopy. All chemicals tested in this study, with the exception of TB and HQ, produced modifications in the morphology of microtubule organization and reduced the fidelity of the spindle apparatus in Hordeum vulgare.

Aneuploidy↗
PubMed1996

Contingency detection and the contingent organization of behavior in interactions: implications for socioemotional development in infancy.

In this report, the authors review studies addressing the issue of contingencies in social and nonsocial contexts during infancy. The review is divided into 4 groups of studies that suggest that (a) young infants detect contingencies unrelated to their behavior; (b) infants detect contingencies involving their behavior; (c) the study of contingency is pertinent for addressing behavioral organization within parent-infant interaction; and (d) there is a link between behavioral contingency in early infancy and global measures of socioemotional development that are predictive of social functioning at later points during childhood. Throughout the report, the pertinence of infant emotional responses during contingency-related tasks is emphasized. Finally, the authors delineate certain enduring questions regarding contingency experience in infancy and suggest ways of organizing research to address some of them.

Emotions↗
PubMed1996

Effects of a series of metalloporphyrins on adrenal, testicular and thyroid function in rats.

We have extended our earlier studies [Pharmacology 1986;34:9-16] on the effects of certain synthetic heme analogues and cobalt chloride (CoCl2) on endocrine functions mediated by the hypothalamic-pituitary axis to examine specifically the ability of Sn-protoporphyrin (SnPP) and Sn-mesoporphyrin (SnMP) to perturb adrenal, testicular and thyroid function since there is interest in the use of Sn(tin)-porphyrins in the treatment of hyperbilirubinemia of the newborn. SnPP and SnMP when administered to adult male rats did not alter serum corticosterone, testosterone, thyroxine or triiodothyronine levels when compared to control animals. In addition, administration of exogenous adrenocorticotrophic hormone produced an increase in serum corticosterone levels that was comparable in placebo-treated and SnPP- and SnMP-treated animals. These studies involved doses of both compounds substantially greater than those used clinically. The results clearly indicate that SnMP, presently the compound of choice for use in newborns, and SnPP do not in the doses studied impair adrenal, testicular and thyroid function in vivo.

Adrenal Glands↗