Glycated hemoglobin reference limits obtained by high performance liquid chromatography in adults and pregnant women

Pentachlorophenol (PCP) and molybdate have been shown to inhibit the sulfoconjugation of various chemicals in rats and therefore are useful to examine the role of sulfoconjugation on the toxicity of a chemical. PCP inhibits sulfation by competing with substrates for phenol-sulfotransferases, but not hydroxysteroid-sulfotransferases. In contrast, molybdate decreases sulfation by limiting sulfate availability and thereby decreasing the synthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which is the obligate cosubstrate for sulfation. Therefore, it was of interest to determine whether PCP or molybdate is effective in decreasing the in vivo sulfation of dehydroepiandrosterone (DHEA), which is a substrate for hydroxysteroid-sulfotransferases. PCP (40 micromol/kg ip) or molybdate (7.5 mmol/kg po) was given 45 min and 4 h, respectively, prior to the start of DHEA infusion. The effects of these two sulfation inhibitors on DHEA sulfation were dependent on the rate of DHEA infusion in rats. PCP had different effects on the sulfation of various infusion rates of DHEA in rats. PCP had little effect on the sulfation after the two lowest infusion rates of DHEA (12.5 and 25 mg/kg) and actually increased (233%) DHEA-sulfate serum concentrations with the highest DHEA infusion rate (50 mg/kg). Although molybdate had little affect on the sulfation of the lowest DHEA infusion rate, it significantly decreased (50-85%) DHEA-sulfate serum concentrations with the two higher DHEA infusion rates. These data indicate that molybdate, unlike PCP, decreases the sulfation of DHEA and may be a useful tool to decrease the sulfation of other substrates of hydroxysteroid-sulfotransferases.     

Conditioned fear-induced tachycardia in the rat: vagal involvement

The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.     

Minimal brain dysfunction in childhood

Minimal (minor) dysfunction of brain (MDB) is the peculiar form among other consequences of perinatal damages of nervous system. The problems of organization of medical care for children with MDB at preschool age are very important. 106 patients with MDB aged 3-8 years were examined. Detailed clinical-neurological, neuropsychological, instrumental and some other forms of examinations were performed including data about postnatal development. It is demonstrated that MDB may be considered as a diffuse cerebral dysregulation, conditioned by a delay of maturation of some connections between different CNS regions. Leading levels of maximal dysregulation are identified. A necessity was emphasized of early revelation, prolonged follow-up and purposeful rehabilitation of such patients.     

Atrioventricular valve function after single patch repair of complete atrioventricular septal defect in infancy: how early should repair be attempted?

BACKGROUND: Though repair of complete atrioventricular septal defect in infancy has become routine at most centers, it is not unusual for very young infants to be managed medically because of concerns about the fragility of the atrioventricular valve tissue. METHODS: Since July 1992, seventy-two infants have undergone primary repair of complete atrioventricular septal defects at a median age of 3.9 months (40% < 3 months). A single-patch technique was used in all patients. The cleft was closed completely in 61 patients and partially (n = 10) or not at all (n = 1) in select patients at risk for valve stenosis. Left atrioventricular valve annuloplasty was performed in 18 patients. On the basis of transesophageal echocardiographic findings, 10 patients were returned to bypass for revision of the valve repair. RESULTS: There was one early death in a patient with single left papillary muscle, no early reoperations, and no new permanent arrhythmias. Only three patients had moderate left atrioventricular valve regurgitation at discharge. During a median follow-up of 24 months, there was one late death and five reoperations for left atrioventricular valve regurgitation (n = 2) and/or systemic outflow obstruction (n = 4). Follow-up left atrioventricular valve regurgitation was moderate in three patients, mild in 14, and none/trace in 54. Age had no relation to postoperative atrioventricular valve regurgitation, death, or reoperation. CONCLUSIONS: Despite concerns about fragility of valve tissue in very young patients, excellent results can be achieved with meticulous techniques. From neonates to older infants, age at repair does not influence outcome or valve function.     

Identification of pentosidine as a native structure for advanced glycation end products in beta-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis

beta-2-Microglobulin (beta-2m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA). Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta-2m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta-2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in beta-2m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived beta-2m-containing amyloid fibrils to the pathogenesis of DRA.