Neonatal erythrocytes

P9. Perona, G., Guidi, G. C., Piga, A., Cellerino, R., Milani, G., Colautti, P., Moschini, G., and Stievano, B. M Neonatal erythrocyte glutathione peroxidase deficiency as a consequence of selenium imbalance during pregnancy. Br. J. Haematol. 42,567-574 (1979). 

The binding of drugs to various body tissues appears to vary with age for example, digoxin binding to erythrocytes is higher in neonates than in adults. This may be due to the increased number of binding sties on neonatal erythrocytes. ... 

Brugnara C, Platt OS. 1998. The neonatal erythrocyte and its disorders. In Nathan DG, Orkin SH, eds. Nathan and Oski s Hematology ofinfancy and Childhood. 5th ed. Philadelphia WB Saunders. Pp. 19-52. 

Chisolm JJ Jr, Brown DH. 1979. Micromethod for zinc protoporphyrin in erythrocytes Including new data on the absorptivity of zinc protoporphyrin and new observation in neonates and sickle cell disease. Biochem Med 22 214-237. 

After 62 days, no observable effect on reproduction, neonatal growth, survival, or development. After 12 weeks, males had decreased hemoglobin and erythrocytes. After 2 years, no significant adverse effects on growth, survival, reproduction, or development (Schwetz etal. 1978 USEPA 1980 McConnell etal. 1980)... 

Pharmacokinetics Rapidly, completely absorbed from G1 tract rectal absorption variable. Widely distributed to most body tissues. Acetaminophen is metabolized in liver excreted in urine. Dichloralphenazone is hydrolyzed to active compounds chloral hydrate and antipyrine. Chloral hydrate is metabolized in the liver and erythrocytes to the active metabolite trichloroethanol, which maybe further metabolized to inactive metabolite. It is also metabolized in the liver and kidneys to inactive metabolites. The pharmacokinetics of isometheptene is not reported. Removed by hemodialysis. Half-life Acetaminophen 1-4 hr (half-life is increased in those with liver disease, elderly, neonates decreased in children). 

McLeod HL, Krynetski EY, Wilimas JA et al. Higher activity of polymorphic thiopurine 5-methyltransferase in erythrocytes from neonates compared to adults. Pharmacogenetics 1995 5 281-286. 

Patients with Refsum disease may have extremely high phytanic acid levels, up to 1500 pmol/1, whereas pristanic acid is low (< 1 pmol/1) as a consequence of the phytanoyl-CoA hydroxylase deficiency. Less pronounced phytanic acid elevations will be observed in RCDP type 1 patients, which applies to both the classical form as well as the variant forms. Values may range from 200 to 900 pmol/1, somewhat depending on age. There is some discussion on the time of onset of phytanic acid accumulation in the classical neonatal RCDP-patients. Normal plasma phytanic acid levels (0.7-5.8 pmol/1) were recorded in the authors laboratory in patients aged less than 1 week. Two- to three-week-old RCDP patients had increased phytanic acid levels of 9.1 -13.2 pmol/1. Classical patients invariably had undetectable plasmalogen levels of the erythrocytes at any age. 

Neonatal samples and individuals with a decreased erythrocyte life spans show high or increased values. 

Four preterm neonates with posthemorrhagic ventricular dilatation developed severe metabolic acidosis after being given acetazolamide (33). The acidosis suddenly disappeared after a transfusion of packed erythrocytes, which was attributed to the citrate contained in the blood. 

Heme oxygenase is the rate-limiting step in the produetion of CO and its activities account for 86% of endogenous CO produetion the remaining 14% is derived from nonheme sourees. The lifespan of red blood cells is approximately 120 days the older the erythrocyte the greater is its CO output. In neonates, red blood cells have a shorter lifespan and relative to erythrocytes of adults, they produce two to three times more CO (Fallstrom, 1968). HO-2 is activated during neuronal stimulation by phosphorylation by the enzyme CK2 (Boehning et al, 2003). 

In about 90% of all neonates, jaundice occurs after the first 2-5 days of life and rarely exceeds 6 mg/dl serum bilirubin. In premature infants, bilirubin levels can rise to 10-12 mg/dl. The cause is related to a number of factors .) reinforced degradation of haemoglobin as a result of the short erythrocyte survival span of 70-90 days (120 days in adults), (2.) reduction in cellular transport proteins, above all ligandin, (i.) deficiency of uri-dyltransferase and glucuronosyltransferase, and (4.) increasing intestinal absorption of meconium bilirubin. 

Petrich C, Goebel U. Vitamin C-induced damage of erythrocytes in neonates. J Pediatr 1989 114(2) 341-2. 

Smith J E, Dever M, Smith J et al 1992 Post-transfusion survival of Cr-labeled erythrocytes in neonatal foals. Journal of Veterinary Internal Medicine 6 183-185 So K W, Fok T F, Ng P C et al 1997 Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants. Archive of Diseases in Childhood 76 F43-F46 Sosa Ledn L A, Davie A J, Hodgson 0 R et al 1995 The effects of tonicity, glucose concentration and temperature of an oral rehydration solution on its absorption and elimination. Equine Veterinary Journal Supplement 20 140-146... 

In infants, even in the absence of disease, the concentration of bflirubin rises after birth because of the enhanced erythrocyte destruction. Its concentration peaks about die third to fifth day of hfe. Conjugation of bilirubin is relatively poor in the neonate as a result of immature liver function. 

Pyruvate Idnase deficiency (OMIM 266200) is the most common cause of nonspherocytic hemolytic anemia due to defective glycolysis. The allelic frequency is estimated to be around 2%. The consequent lack of sufficient energy, which is required for normal functioning and cellular survival, shortens the life span of the mature PK-deficient erythrocyte. Consequently, PK-deficient patients display a phenotype of nonspherocytic hemolytic anemia albeit with variable clinical severity. The clinical symptoms vary from neonatal death to a well-compensated hemolytic anemia. Patients benefit in general from a splenectomy. Pyruvate kinase deficiency is transmitted as an autosomal recessive disease. To date, more than 130 mutations in PKLR have been reported to be associated with pyruvate kinase deficiency (see Figure 21-10 for overview see reference 221). Most (70%) of these mutations are missense mutations affecting conserved residues in structurally and functionally important domains of PK. Splice site mutations, a deletion. 

There are several reports by Jones and co-workers dealing with the purification, properties and conformation of the orotate phosphoribosyltransferase and orotidylic acid decarboxylase enzyme complex present in mouse Ehrlich ascites cells [135-137]. Multiple molecular forms of orotidylic acid decarboxylase from human erythrocytes and human liver were studied by O Sullivan and co-workers [138,139]. A bifunctional enzyme complex of orotate phosphoribosyltransferase and orotidylic acid decarboxylase occurs also in mouse liver and brain [140], regardless of the developmental stage of the animal. Both enzyme activities remained co-ordinate in fetal, neonatal, immature and adult liver and brain. 

Neonatal rats, 21 days old Acute dosing Pb acetate Dose-response relationship, P5N versus PbB in erythrocytes Inhibition of P5N was linearly inversely related to PbB, 77-108 pg/dl Konantakieti etal. (1986)... 

Female rabbits orally dosed for 5 days with 17 iM Pb showed reduced enzyme activity in erythrocytes, bone marrow, and liver (Zareba and Chmielnicka, 1992). These workers also noted an increased activity of the 6-ALA-S enzyme in these rabbits. Gerber et al. (1978) reported that oral dosing of neonatal mice with Pb at 0—17 days of age showed statistically significant reductions in brain enzyme activity at aU time points. 

Female rabbits (Zareba and Chmielnicka, 1992), red-tailed hawks (Redig et al., 1991), and adult rats (Roels et al., 1978) with relatively high oral Pb dosings had elevated ZPP, but the dosing level in adult mice was not sufficient to produce increases over controls. Neonatal rats acutely dosed with Pb acetate showed inhibition of P5N activity but at relatively high systemic levels in the PbB range 77—108 tig/dl (Konantakieti et al., 1986). Inhibition of P5N activity was also noted with oral Pb in the mouse (erythrocytes and marrow cells) and rabbit studies of Tomokuni et al. (1989) and Swanson et al. (1980), respectively. 

Konantakieti, C., Beuthin, F.C., Louis-Feidinand, R.T., 1986. Erythrocyte pyrimidine 5 -nucleo-tidase inhibition by acute lead exposure in neonatal rats. J. Biochem. ToxicoL 1, 51—59. 

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