Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model.

OBJECTIVE: Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model. METHODS: Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without<440-nm wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50% blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects of phototherapy are expressed as ratios of serum total (TB) and unbound (UB) bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each LED to determine photo-oxidative stress. RESULTS: Values < 1.00 indicate effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89, 1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively. In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23 after exposure to blue, filtered blue, FB50, mixed, green LED, and control, indicating side-effects (> 1.00), respectively. CONCLUSIONS: Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress. PRACTICE IMPLICATIONS: Combined blue and green spectra might be effective against neonatal hyperbilirubinemia.

Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease.

Metabolomics is a powerful new technology that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and nondiseased status information. Deciphering the molecular networks that distinguish diseases may lead to the identification of critical biomarkers for disease aggressiveness. However, current diagnostic methods cannot predict typical Jaundice syndrome (JS) in patients with liver disease and little is known about the global metabolomic alterations that characterize JS progression. Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication, and therapy. Therefore, the aim of this study is to find the potential biomarkers from JS disease by using a nontarget metabolomics method, and test their usefulness in human JS diagnosis. Multivariate data analysis methods were utilized to identify the potential biomarkers. Interestingly, 44 marker metabolites contributing to the complete separation of JS from matched healthy controls were identified. Metabolic pathways (Impact-value≥0.10) including alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies were found to be disturbed in JS patients. This study demonstrates the possibilities of metabolomics as a diagnostic tool in diseases and provides new insight into pathophysiologic mechanisms.

Orina oscura e ictericia como signos de peligro en malaria por Plasmodium falciparum en Colombia / Dark urine and jaundice as warning signs in Plasmodium falciparum malaria in Colombia

INTRODUCCIÓN: el reconocimiento temprano de signos de peligro en el paciente con malaria permite identificar tempranamente el paciente en riesgo de hacer complicaciones clínicas, para ofrecerle un tratamiento adecuado y oportuno. La ictericia y orina oscura son signos frecuentes que pueden alertar sobre la instauración de una malaria complicada. OBJETIVO: estudiar en el paciente malárico la relación entre ictericia y orina oscura con disfunción hepática o renal y anemia, para establecer su utilidad como signos de peligro. MÉTODOS: se analizó información clínica y de laboratorio de 199 pacientes con malaria por Plasmodium falciparum, de un estudio de casos y controles realizado en Colombia. Se estudió la asociación entre orina oscura e ictericia con alteraciones del uroanálisis, pruebas de función hepática y renal, y hemoglobina. RESULTADOS: hubo asociación entre orina oscura y hemoglobinuria (OR= 236; 63-867), hematuria (OR= 3,2; 1,6-6,6), proteinuria (OR= 2,3; 1-5,3) y bilirrubinuria (OR= 2,1; 1-4,4). La ictericia estuvo presente en 31 por ciento de pacientes con disfunción renal (OR= 2,7; 1,1-6,4) y en 22 por ciento de pacientes con disfunción hepática (OR= 2,1; 0,9-4,5). Se encontró alta probabilidad de presentar ictericia en los pacientes con bilirrubina sérica total >25,6 µmol/L (OR= 6,1; 2,7-13,4) y nitrógeno ureico en sangre> 7,14 mmol/L (OR= 3,5; 1,4-8,5). CONCLUSIONES: la ictericia es un signo de peligro en el paciente malárico que se asocia con disfunción hepática y renal. La orina oscura no se asoció con disfunción renal o hepática, pero se explicó por bilirrubinuria, hematuria y proteinuria, que pueden ser indicadores tempranos de daño; debe estudiarse la orina oscura para aclarar su relación con el daño renal y hepático en malaria.

INTRODUCTION: early recognition of warning signs in malarial patients allows timely identification of the patient at risk of severe malaria and provides opportune treatment. Jaundice and dark urine are frequent signs that can alert to the occurrence of severe malaria. OBJECTIVE: to study the relationship between jaundice and dark urine with impaired liver and/or kidney function and anemia in malarial patients, and explore their role as warning signs. METHOD: clinical and laboratory data from 199 patients with Plasmodium falciparum malaria, belonging to a case control study conducted in Colombia, were analyzed. the association between dark urine and jaundice with impairment in the urine analysis, the hepatic and renal function test, and hemoglobin were studied. RESULTS: there was association between dark urine and hemoglobinuria (OR= 236, 63-867), hematuria (OR=3.2, 1.6-6.6), proteinuria (OR= 2.3, 1-5.3) and bilirubinuria (OR=2.1, 1-4.4). Jaundice was present in 31 percent of patients who had renal dysfunction (OR= 2.7, 1.1-6.4) and in 22 percent of those with liver dysfunction (OR= 2.1, 0.9-4.5). Jaundice was more likely in patients with total bilirubin > 25.6 µmol/L (OR= 6.1, 2.7-13.4) and blood ureic nitrogen > 7.14 mmol/L (OR= 3.5, 1.4-8.5). CONCLUSIONS: jaundice in patients with malaria may be considered as a warning sign associated with liver and kidney dysfunction. Dark urine was not associated with kidney or liver dysfunction, but was related to bilirubinuria, hematuria and proteinuria, which can be early indicators of failure; dark urine must be studied to clarify its relationship with liver and kidney failure in malaria.

[Dark urine and jaundice as warning signs in Plasmodium falciparum malaria in Colombia]. / Orina oscura e ictericia como signos de peligro en malaria por Plasmodium falciparum en Colombia.

INTRODUCTION: early recognition of warning signs in malarial patients allows timely identification of the patient at risk of severe malaria and provides opportune treatment. Jaundice and dark urine are frequent signs that can alert to the occurrence of severe malaria. OBJECTIVE: to study the relationship between jaundice and dark urine with impaired liver and/or kidney function and anemia in malarial patients, and explore their role as warning signs. METHOD: clinical and laboratory data from 199 patients with Plasmodium falciparum malaria, belonging to a case control study conducted in Colombia, were analyzed, the association between dark urine and jaundice with impairment in the urine analysis, the hepatic and renal function test, and hemoglobin were studied. RESULTS: there was association between dark urine and hemoglobinuria (OR = 236, 63-867), hematuria (OR = 3.2, 1.6-6.6), proteinuria (OR = 2.3, 1-5.3) and bilirubinuria (OR = 2.1, 1-4.4). Jaundice was present in 31 % of patients who had renal dysfunction (OR = 2.7, 1.1-6.4) and in 22 % of those with liver dysfunction (OR = 2.1, 0.9-4.5). Jaundice was more likely in patients with total bilirubin > 25.6 micromol/L (OR = 6.1, 2.7-13.4) and blood ureic nitrogen > 7.14 mmol/L (OR = 3.5, 1.4-8.5). CONCLUSIONS: jaundice in patients with malaria may be considered as a warning sign associated with liver and kidney dysfunction. Dark urine was not associated with kidney or liver dysfunction, but was related to bilirubinuria, hematuria and proteinuria, which can be early indicators of failure; dark urine must be studied to clarify its relationship with liver and kidney failure in malaria.

Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient.

Hepatic excretion of non-bile acid organic anions is reported to be ATP-dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin-Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP-dependent organic anions, uptake of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase-inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP-dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague-Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [14C]-pravastatin (0.3 mumol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co-stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the K(m) was much higher and Vmax was much lower than corresponding values in SD rats. This coincided well with the marked reduction in vivo biliary excretion of pravastatin in jaundiced rats.

The development of hepatitis C antibody shortly after acute icteric non-A non-B hepatitis.

OBJECTIVE: To determine the relationship between the development of hepatitis C antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN: Retrospective analysis of sera from patients with acute non-A non-B hepatitis. SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included a typical clinical illness, accompanied by an alanine aminotransferase level of more than 2.5 times the upper limit of normal (normal, less than or equal to 40 U/L) and negative serological test results for acute hepatitis A and B. MAIN OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128 patients who fulfilled the inclusion criteria. In these patients, antibody was detected between one week and 32 weeks after the onset of dark urine; more than half the patients (54%) had seroconverted by four weeks and a third (34%) developed antibodies within two weeks. Of 20 patients who had sera collected within four weeks of the onset of dark urine, 14 (70%) had developed antibody. CONCLUSION: These results suggest that in patients with community-acquired hepatitis C, seroconversion occurs significantly earlier than is observed in patients who have been infected by blood transfusion. Sera taken shortly after the onset of symptomatic hepatitis C may be useful in the diagnosis of this condition.

Identification and clinical examination of jaundiced rats.

Rats with or without spontaneously occurring jaundice were clinically examined. Jaundiced rats had five-fold higher serum bilirubin concentrations than control animals. About 90% of serum bilirubin in the jaundiced animals was in conjugated form. Control and jaundiced rats did not differ with respect to clinical signs such as alertness, stance, hair coat, position of eyes, discharge from eyes and nose, and cleanliness of anal orifice. While examined individually, jaundiced rats could not be identified readily on the basis of a yellow colour of sole of feet, nose, ears and tail. When kept together with control rats, jaundiced rats could be selected reasonably well. Urines of jaundiced rats had a more intense yellow colour than urines of control animals. Rats with jaundice were significantly more active in a small open field test than control rats.

Tubular dysfunction in the deeply jaundiced patient with hepatorenal syndrome.

We examined beta 2-microglobulin (B2MG) excretion, an index of tubular function, in patients with hepatorenal syndrome, in whom tubular function is generally regarded as normal. Urine B2MG was significantly higher in these patients than in control patients with normal serum creatinine concentration. Patients with high urine B2MG concentration had markedly higher serum bilirubin than did patients with normal values (31 +/- 3 vs. 10 +/- 8 mg%, p less than 0.001), whereas prothrombin activity, serum albumin and serum B2MG concentration were similar. A "threshold" serum bilirubin concentration of about 23 mg% differentiated patients with normal and high urine B2MG values. Renal morphology at autopsy was unremarkable in both groups. Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice. This measurement cannot, therefore, be used to make a diagnosis of acute tubular injury, as due to aminoglycosides, in such patients.

Urinary porphyrin pattern in liver damage.

Known techniques were used with slight modification to analyse and quantify porphyrins in the urine samples of normal human subjects, of clinically established jaundice cases and of women taking oral contraceptives. The results indicate that the urinary porphyrin pattern can be a useful tool in the detection of early liver injury.

PIP: This study used modifications of methods developed by Harmsen and Strik for total porphyrin and for porphyrin metabolites to investigate porphyrin patterns in urine samples from clinically established jaundice cases, women taking oral contraceptives (OCs), and healthy human subjects. Determination of urinary porphyrin patterns was carried out by use of thin-layer chromatography. The ranges of total porphyrins (20-120 mcg/liter), uroporphyrin (6-45 mcg/liter), and coproporphyrin (9-63 mcg/liter) in urine samples from normal subjects were within the limits reported in the literature. As expected, total porphyrins were higher in the jaundiced patients. There was a slight but not statistically significant increase in total porphyrin xcretion and a slight decrease in the coproporphyrin/uroporphyrin ration in OC users. Recoveries using this technique were 80-85% and reproducible. These results suggest the value of this method in monitoring for occupational and environmental exposure to xenobiotics. Future screening is planned to detect liver injury in childred with Indian childhood cirrhosis or kwashiorkor.

Urinary tract infection presenting with jaundice.

Jaundice was the presenting feature in an 8-year-old girl suffering from urinary tract infection (UTI) due to Escherichia coli. The jaundice cleared with the cure of the infection. The mechanisms of jaundice complicating UTI are discussed, and the importance of urine culture in infants and children with jaundice is stressed.

Increased D-glucaric acid excretion by jaundiced patients.

The urinary excretion of D-glucaric acid, a catabolite of glucuronic acid, is considered to be a reliable index of the state of hepatic microsomal enzyme activity. Because enzyme activity may be altered in liver disease, we examined the effect of liver disease on the excretion of this metabolite and its correlation with liver function tests. We studied 89 patients with nonhemolytic jaundice, 39 with viral hepatitis, 33 with obstructive jaundice, six with cirrhosis, and 11 patients with jaundice of mixed etiology. Glucaric acid excretion was significantly increased in all these patients as compared to controls, most pronounced in the obstructive jaundice group. No correlation was found between glucaric acid excretion and concentrations of bilirubin, albumin, globulin, aspartate aminotransferase, alkaline phosphatase, cholesterol, or gamma-glutamyltransferase in serum, even though the concentrations of these analytes did vary with the type of liver disease. We suggest that this increase in glucaric acid excretion is an indication of normal or even increased glucuronidation (UDP-glucuronosyltransferase activity), which occurs in liver disease.