Bilirubin levels

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

When levels of conjugated bilirubin remain high in plasma, a fraction can bind covalently to albumin (delta bilirubin). Because it is bound covalently to albumin, this fraction has a longer half-life in plasma than does conventional conjugated bilirubin. Thus, it remains elevated during the recovery phase of obstructive jaundice after the remainder of the conjugated bilirubin has declined to normal levels this explains why some patients continue to appear jaundiced after conjugated bilirubin levels have returned to normal. 

Results are means of duplicate determinations. Serums are from the routine laboratory. Bilirubin levels are assayed values. 

The oncologist prescribes the normal doses of idarubicin 12 mg/m2 IV daily for 3 days and cytarabine 100 mg/m2 per day by continuous infusion for 7 days to treat her acute myelogenous leukemia. Her baseline laboratory measurements are significant for an elevated WBC count, a creatinine concentration of 2.5 mg/dL (221 pmol/L), and a bilirubin level of 1.6 mg/dL (27 pmol/L). 

Hyperbilirubinemia Abnormally high concentrations of the bile pigment bilirubin in the bloodstream. Hyperbilirubinemia is defined as a total serum bilirubin level greater than 5 mg/dL. 

These results do not have any diagnostic meaning. The dynamics of the ACU values after an operative intervention could be taken into account regarding the existence of metastases. As demonstrated in Figure 12, prognostic relevance can be ascribed to ACU. The rise in ACU value is caused in this case by increase of the bilirubin level under the conditions of the life-threatening inflammatory processes [1],... 

Bilirubin is diazotized with para-sulphonyl benzene diazonium compound and the absorbance of the resulting azobilirubin is measured at 600 nm to determine bilirubin level in the biological fluid e.g., blood serum. In usual practice, a serum blank is run simultaneously by reacting the serum with caffeine, sulphanilic acid and tartaric acid, and the absorbance of the blank is measured at 600 nm which is subsequently subtracted from the azobilirubin absorbance initially obtained before the bilirubin level is finally determined. 

Enhanced bilirubin level may suggest drug toxicity, bile-tract obstruction, hepatitis and hepatic dysfunction,... 

As normal bilirubin level commences from zero, hence conditions responsible for its decrease are practically non-existent,... 

Increased bilirubin levels are caused due to the intake of large doses of such drugs as chloroquine, vitamin K, sulpha-drugs, tetracyclines, paracetamol, nicotinic acid and monoamine oxidase inhibitors (e.g., iproniazid RP 1.0 nialamide RP 1.8 isocarboxazid RP 3.1 phenelzine RP 18 pheniprazine RP31 and tranylcypromine RP 45), where RP designates the Relative Potency based on the tiyptamine potentiation test. The elevated levels are due to hepatic injury, and... 

There are a few medicinals that cause increased bilirubin levels which ultimately enhances AP-levels unless and until a corrective measure is taken in the respective procedure one may be left with false AP-level enhancement. Some typical examples are, namely amitriptyline, chloropropamide, erythromycin, phenylbutazone, sulpha-drugs and tetracyclines. 

Orotic acid and aspartic acid, when given orally to full-term, healthy newborn infants for the first 4 days of life, can significantly lower their serum bilirubin level [187]. The effect of aspartic acid is immediate, whereas that of orotic acid is delayed [187]. 

Hyperbilirubinemias. An elevated bilirubin level (> 10 mg L ) is known as hyperbilirubinemia. When this is present, bilirubin diffuses from the blood into peripheral tissue and gives it a yellow color (jaundice). The easiest way of observing this is in the white conjunctiva of the eyes. 

Above l.Omg/m the liver is unable to handle the increased amounts of red blood cell breakdown products and indirect bilirubin levels rise. Elevations of liver function enzymes may occur, particularly in new employees or those recently exposed to higher levels. There are suggestions of marked individual susceptibility to liver damage, with most not showing effects unless exposures considerably exceed l.Omg/mk ... 

Bilirubin effects depend on the method used for analysis. Interferences in direct serum protein methods are observed at bilirubin levels greater than 5 mg/100 ml (K7). A sample containing 20 mg of bilirubin per 100 ml increased the apparent total protein by 0.2 g/100 ml. Concentrations of bilirubin as high as 20 mg/ml do not effect albumin assays using bromocresol green binding (D12), but have a marked effect on these assays when [2-(p-hydroxyphenylazo)-benzoic acid] (HABA) dye is used (A7b). 

Drug/Lab test interactions Thiazides may decrease serum PBI levels without signs of thyroid disturbance. Thiazides also may cause diagnostic interference of serum electrolyte, blood, and urine glucose levels (usually only in patients with a predisposition to glucose intolerance), serum bilirubin levels, and serum uric acid levels. In uremic patients, serum magnesium levels may be increased. Bendroflumethiazide may interfere with the phenolsulfonphthalein test due to decreased excretion. In the phentolamine and tyramine tests, bendroflumethiazide... 

Hepatic Effects. An animal study revealed that hexachlorobutadiene can affect the liver. However, the effects were less serious compared to effects in the kidney at the same dose. Liver weights were decreased in female rats fed 5 mg/kg/day or greater hexachlorobutadiene for 4 weeks (Jonker et al. 1993b). Histological examinations were not performed. However, evaluation of serum biochemical parameters in males revealed increased enzyme activity (aspartate aminotransferase, p <0.02) and total bilirubin levels (p<0.02) at doses of 20 mg/kg/day (highest dose tested). 

Liver injury is clinically defined as an increase of serum alanine amino transferase (ALT) levels of more than three times the upper limit of normal and a total bilirubin level of more than twice the upper limit of normal [4]. The clinical patterns of liver injury can be characterized as hepatocellular (with a predominant initial elevation of ALT), cholestatic (with an initial elevation of alkaline phosphatase) or mixed. The mechanisms of drug-induced hepatotoxicity include excessive generation of reactive metabolites, mitochondrial dysfunction, oxidative stress and inhibition of bile salt efflux protein [5]. Better understandings of these mechanisms in the past decades led to the development of assays and models suitable for studying such toxic mechanisms and for selecting better leads in the drug discovery stage. 

Hepatic Effects. Carbon tetrachloride has been known for many years to be a powerful hepatotoxic agent in humans and in animals. The principal clinical signs of liver injury in humans who inhale carbon tetrachloride are a swollen and tender liver, elevated levels of hepatic enzyme (aspartate aminotransferase) in the serum, elevated serum bilirubin levels and the appearance of jaundice, and decreased serum levels of proteins such as albumin and fibrinogen (Ashe and Sailer 1942 McGuire 1932 New et al. 1962 Norwood et al. 1950 Straus 1954). In cases of acute lethal exposures, autopsy generally reveals marked liver necrosis with pronounced steatosis (Jennings 1955 Markham 1967 Smetana 1939), and repeated or chronic exposures leads in some cases to fibrosis or cirrhosis (McDermott and Hardy 1963). 

Detection of liver injury has commonly been associated with alternations in serum levels of certain hepatic enzymes and proteins. Elevation in bilirubin levels following exposure (Barnes and Jones 1967) has been detected in humans, as have decreased serum levels of secreted liver proteins (e.g., albumin and fibrinogen) (Ashe and Sailer 1942 McGuire 1932 New et al. 1962 Norwood et al. 1950 Straus 1954). Elevations in serum levels of enzymes (e.g., ALT, AST, LDFI, OCT) have been reported following acute- and intermediate-duration exposures to carbon tetrachloride in animals (Bruckner et al. 1986 FI ayes et al. 1986 Sakata et al. 1987). 

The 60 allele (-3279 T>G) in PBREM is partially linked with the 28 allele namely, the 60 haplotype without the 28 allele is also found (37,38,39) (Fig. 3). Trends of 60 haplotype-dependent decrease in SN-38 G formation (38,47) and increase in total bilirubin levels (38) have been observed in Japanese however, contribution to irinotecan severe toxicides of the 60 allele alone was not clearly demonstrated (41,47,49). 

As for the Block C (exons 2-5) haplotype IB, its significant associations with reduced AUC ratios and neutropenia were not clearly demonstrated, but a possible contribution under co-occurrence with haplotype 60 was suggested (38,47). In fact, the combinatorial haplotype 60 - IB increased bilirubin levels in healthy Japanese subjects (50). Because the frequency of IB homozygotes is rather low in Asians (39), further studies in other ethnic populations would clarify the role of 60- IB in irinotecan treatment. 

Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention. 

In die peripheral blood system, crocetin derivatives prevent an elevation in bilirubin levels [3] and also reduce elevated levels of serum cholesterol and triglyceride [4]. Anti-tumor activity of saffron is observed in mice transplanted with several types of tumor cell lines including sarcoma 180, Ehrlich ascites carcinoma, and Dalton s lymphoma ascites... 

Treatment of male Charles-Foster rats with sublethal doses of xylene (0.2 mL of 5 mmol/L extra-pure xylene solution on alternate days for 30 days isomeric composition not indicated) resulted in slight increases of serum aspartate and alanine aminotransferase and alkaline phosphatase activities and bilirubin concentration (Rana Kumar, 1993). A slight increase in alanine aminotransferase activity was also observed after a 3.5-week treatment of male Wistar rats with zneto-xylene (800 mg/kg bw per day on five days per week, by gavage) (Elovaara et al., 1989). Inhalation exposure of C3H/HeJ mice to /jora-xylenc (1200 ppm [5200 mg/m ], 6 h per day for four days) did not affect the serum alanine or aspartate aminotransferase or lactate dehydrogenase activities, or bilirubin level (Selgrade et al., 1993). 

Jaundice (also called icterus) refers to the yellow color of skin, nail beds, and sclerae (whites of the eyes) caused by deposition of bilirubin, secondary to increased bilirubin levels in the blood (hyperbilirubinemia, Figure 21.10). Although not a disease, jaundice is usually a symptom of an underlying disorder. 

Definition and causes of jaundice Jaundice (icterus) refers to the yellow color of the skin, nail beds, and sclerae caused by deposition of bilirubin, secondary to increased bilirubin levels in the blood. There are three major forms of jaundice hemolytic jaundice, caused by massive lysis of red blood cells, releasing more heme than can be handled by the reticuloendothelial system obstructive jaundice, resulting from obstruction of the bile duct and hepatocellular jaundice, caused by damage to liver cells that decreases the liver s ability to take up and conjugate bilirubin. In addition, neonatal jaundice is caused by the low activity of hepatic glucuronylation of bilirubin, especially in premature infants. 

The hepatobiliary agents are removed from the blood by hepatocytes in the liver through an active transport mechanism.677 They are cleared from the plasma as anions by the same general mechanism as bilirubin so that high bilirubin levels can competitively inhibit the transport of "mTc-IDA agents through the liver.553... 

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