We investigated alpha-adrenoceptor-mediated positive chronotropic action in children using a pharmacological autonomic function test. Under cardiac vagal and sympathetic blockade, chronotropic responses to intravenous infusion of an alpha-agonist, phenylephrine, were determined in 129 patients with suspected autonomic dysfunction. Heart rate changes to phenylephrine infusion (0.4 microg/kg/min) for 5 minutes ranged from -2 to 50 beats/min (mean +/- SD, 13.8 +/- 9.7 beats/min). alpha-Adrenoceptor-mediated chronotropic (APC) action more than 5 beats/min was observed in 88 (68%) subjects. APC was negatively correlated with age. Multivariate analysis showed that APC was correlated negatively with beta-sympathetic tone and positively correlated with intrinsic heart rate. These results suggest that the alpha-adrenoceptor-mediated chronotropic action is a developmental phenomenon and may play an important role in controlling heart rate in response to cardiac sympathetic activation.

Adolescent↗

PubMedDate not supplied

Scavenging effect of 5-aminosalicylic acid on neutrophil-derived oxidants. Possible contribution to the mechanism of action in inflammatory bowel disease.

Inflammatory phagocytic leukocytes produce superoxide and hydrogen peroxide and secrete myeloperoxidase (MPO) into the extracellular medium. MPO catalyzes the oxidation of Cl- by H2O2 to yield chlorinated oxidants (e.g. HOCl and NH2Cl), which have been shown to induce pathologic changes in mucosal function. We examined the ability of 5-aminosalicylic acid (5-ASA), a drug used to treat inflammatory bowel disease (IBD), to inhibit oxidation of L-cysteine by NH2Cl, HOCl and H2O2. NH2Cl and HOCl were especially strong oxidants against L-cysteine. 5-ASA prevented L-cysteine oxidation by NH2Cl and HOCl; an interaction associated with the formation of characteristic absorption spectra due to the oxidation of 5-ASA was observed. NH2Cl and HOCl evoked characteristic increases in short-circuit current (Isc), indicative of net electrolyte transport, when added to the serosal side of stripped rat colon mounted in Ussing chambers. Premixing of NH2Cl with 5-ASA 10 min before addition to the tissue markedly reduced the secretory response to NH2Cl. In contrast, 5-ASA immediately reduced the response to HOCl. The reduction in the functional response to NH2Cl and HOCl by 5-ASA may contribute to its mechanism of action in the treatment of the symptoms of IBD.

Aminosalicylic Acids↗

PubMedDate not supplied

Detection of Palmaz-Schatz stent by ultrafast CT.

We present a case of Palmaz-Schatz stent in the anterior descending coronary artery in a patient in whom restenosis occurred repeatedly after balloon angioplasty. The location of the stent was confirmed by ultrafast CT. The Palmaz-Schatz stent is barely visible by fluoroscopy and confirmation of its location by fluoroscopy is difficult after failure of stent delivery. However, ultrafast CT enabled the clear detection of a Palmaz-Schatz stent without artifacts and may be valuable in confirming its location.

Aged↗

PubMedDate not supplied

Anorexia nervosa with elevated serum TSH.

Low or normal serum TSH concentration is common during fasting and in patients with anorexia nervosa. We report here four patients with anorexia nervosa who had elevated serum TSH, low T3 and low free T4 levels when the initial diagnosis was made. Also, an appearance of TSH peak in response to TRH was delayed, but T3 responsiveness to TRH was normal. All patients were clinically euthyroid with negative serum thyroid autoantibodies and without goiter. Following weight gain, basal levels of serum T3, free T4, and TSH, as well as TSH responsiveness to TRH, returned almost to normal. The data indicated that these patients with anorexia nervosa before refeeding had either a latent transient primary hypothyroidism or the low T3 syndrome associated with an inappropriately high secretion of TSH, probably a new condition that is related to their pretreatment nutritional state.

Adolescent↗

PubMedDate not supplied

Pancreatic abnormalities in patients with eating disorders.

In patients with eating disorders, we evaluated pancreatic abnormalities using serum elastase 1 measurement by RIA and the 50 g oral glucose tolerance test (50 g OGTT). Twenty-one patients had anorexia nervosa (AN) with bulimia and vomiting (AN-B group), 30 had AN without bulimia or vomiting (AN-R group), and 25 had bulimia with normal body weight (B group). The serum elastase 1 level was determined on admission and repeated after body weight gain in 43 anorectic patients. The 50 g OGTT was performed within 2 weeks after admission. The serum elastase 1 level in the AN-B group (363 +/- 47 ng/dl, M +/- SE), and in the AN-R group (352 +/- 37) were significantly higher than that in the B group (242 +/- 18) or in the healthy female controls (191 +/- 10; n = 13). A significant decrease of serum elastase 1 was observed before and after body weight gain; however, there was no significant correlation between the serum elastase 1 level and insulin response to the 50 g OGTT. Elevation of the serum elastase 1 level in AN suggests pancreatic abnormalities other than those related to endocrinological events.

Adult↗

PubMedDate not supplied

Pretreatment with 5-fluorouracil enhances cytotoxicity and retention of DNA-bound platinum in a cisplatin resistant human ovarian cancer cell line.

A combination of 5-fluorouracil (5-FU) and cisplatin (cis-Diamminedichloroplatinum(II); CDDP) was administered to CDDP-sensitive (A2780) and -resistant (2780CP) human ovarian cancer cell lines in vitro in order to investigate the effects of 5-FU pretreatment on CDDP cytotoxicity, removal of DNA-bound platinum (Pt-DNA) and cellular glutathione (GSH) level. The cells were incubated with various doses of 5-FU for 24 hours, and then exposed to various doses of CDDP after a drug-free interval of 24 hours. Pretreatment with 5-FU (0.5 - 2.0 microg/ml) augmented the cytotoxicity of CDDP in 2780CP cells, but did not affect A2780 cells. 2780CP cells lost 23.0 to 41.9% of their total Pt-DNA determined by flameless atomic absorption spectrophotometry at 6 to 24 hours after exposure to 10.0 microg/ml CDDP alone; nevertheless, 1.0 microg/ml 5-FU pretreatment caused a significant delay in removal of Pt-DNA (3.8, 1.5 and 7.2% at 6, 12 and 24 hours after exposure to CDDP, respectively). At 24 hours after 15.0 microg/ml CDDP exposure, 2780CP cells pretreated with 5-FU lost only 15.7% of their total Pt-DNA, although the platinum removal rate with CDDP alone was 28.4%. The GSH levels in 2780CP cells were similar in the presence or absence of 5-FU pretreatment. These data indicated that 5-FU pretreatment enhances the cytotoxicity of CDDP and reverses CDDP resistance in 2780CP cells and that its mechanism is related to the inhibitory effect of 5-FU on DNA repair, and not to cellular GSH levels.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Expression of tenascin in mesangial injury in experimental glomerulonephritis.

The distribution of tenascin (TN) in the kidneys in relation to embryogenesis, the normal glomerulus and various glomerular diseases has been studied immunohistochemically. However, the existence of TN protein and mRNA simultaneously has never been reported in reversible mesangial proliferative glomerulonephritis (MPGN). In this study, by immunohistochemical methods and in situ hybridization, we investigated the expression of TN in injury to glomerular mesangial cells. Anti-Thy 1.1 mesangial proliferative glomerulonephritis was induced in Wistar rats by injection of antirat thymocyte plasma. After injection, the rats were sacrificed on days 4, 7, 10 and 14. Immunohistochemically, slight staining of TN was detected in normal glomeruli. An increase in staining was observed in the mesangial areas during the mesangial proliferative phase (days 4, 7 and 10). It decreased on day 14. Focal staining of TN in Bowman's capsule and the periglomerular region was also noted during the mesangial proliferative phase. TN mRNA could not be detected in normal glomeruli by in situ hybridization, but it was observed in the mesangial areas during the mesangial proliferative phase. Focal expression of TN mRNA was noted in Bowman's capsular epithelial cells and periglomerular cells after injection. TN mRNA-positive cells were localized to mesangial, Bowman's capsular and periglomerular areas of hypercellularity and were significantly associated with an increase in TN staining areas. In conclusion, the results of this study prove that TN is a component of the normal mesangial matrix, and that it is induced by mesangial, Bowman's capsular and periglomerular cells after mesangial injury. We could not determine the role of TN in Bowman's capsular and periglomerular areas, but a reversible MPGN model has been reported to show an irreversible progressive course in TN knockout mice. In reversible MPGN it is considered that the role of TN in the mesangial areas may be related to the process of mesangial repair.

Animals↗

PubMedDate not supplied

Developmental changes in alpha-tocopherol, especially during infantile period.

Developmental changes in expression of alpha-TTP after birth were investigated using rats with respect to plasma changes of tocopherols. The expression of alpha-TTP in the neonatal rat liver, which was very low immediately after birth, increased steadily during the two weeks of life before weanling and reached the adult level at 4 weeks. During the suckling period, the plasma ratio of alpha-tocopherol to gamma-tocopherol linearly increased, because plasma alpha-tocopherol was low immediately after birth, increased rapidly during the period, while gamma-tocopherol remained unchanged. The increase in the ratio seemed to correlate with the developmental expression of alpha-TTP in the liver during this period. The ratio also reached the adult level after 4 weeks. The expression of alpha-TTP was investigated using primary cultured rat hepatocytes. The expression of alpha-TTP was found to be extremely low after 20 h of culture. The decrease in alpha-TTP expression was exacerbated by adding epidermal growth factor to the culture medium and was inhibited by adding dexamethasone. These observations suggest that expression of alpha-TTP may be affected by the state of hepatic differentiation. The Western and Northern blot analysis of alpha-TTP in vitamin E deficient and enriched rats were compared to control rats. The decrease of mRNA of alpha-TTP observed in alpha-Toc-enriched rat liver and the increase of mRNA observed in the vitamin E deficient rat liver indicate the synthesis of alpha-TTP, although alpha-TTP itself was not altered.

Animals↗