Demonstration of a geometric isomer of bilirubin-IX alpha in the serum of a hyperbilirubinaemic newborn infant and the mechanism of jaundice phototherapy.
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SUBMITTER: Onishi S
PROVIDER: S-EPMC1162129 | biostudies-other | 1980 Sep
REPOSITORIES: biostudies-other
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Project description:BACKGROUND: In many resource-limited settings, the availability of effective phototherapy for jaundiced infants is frequently hampered by lack of, or inadequate resources to acquire and maintain conventional electric-powered phototherapy devices. This study set out to ascertain maternal experience and satisfaction with a novel treatment of infants with significant hyperbilirubinemia using filtered sunlight phototherapy (FSPT) in a tropical setting with irregular access to effective conventional phototherapy. METHODS: A cross-sectional satisfaction survey was conducted among mothers of jaundiced infants treated with FSPT in an inner-city maternity hospital in Lagos, Nigeria from November 2013 to March 2014. Mothers' experience during treatment was elicited with a pretested questionnaire consisting of closed and open-ended items. Satisfaction was rated on a five-point Likert scale. Correlates of overall maternal satisfaction were explored with descriptive and inferential non-parametric statistics. RESULTS: A total of 191 mothers were surveyed, 77 (40%) of whom had no prior knowledge of neonatal jaundice. Maternal satisfaction was highest for quality of nursing care received (mean: 4.72?±?0.55, median: 5[IQR: 5-5]) and lowest for physical state of the test environment (mean: 3.85?±?0.74, median: 4[IQR: 3-4]). The overall rating (mean: 4.17?±?0.58, median: 4[IQR: 4-5]) and the observed effect of FSPT on the babies (mean: 4.34?±?0.58, 4[IQR: 4-5]) were quite satisfactory. FSPT experience was significantly correlated with the adequacy of information received (p?<?0.0005), test environment (p?=?0.002) and the observed effect of FSPT on the child (p?<?0.0005). Almost all mothers (98.4%) indicated willingness to use FSPT in future or recommend it to others, although some (30 or 15.7%) disliked the idea of exposing newborns to sunlight. CONCLUSIONS: Mothers of jaundiced newborns in this population are likely to be satisfied with FSPT where it is inevitable as an alternative to conventional electric-powered phototherapy. Adequate information, good test environment and friendly nursing care must be ensured for satisfactory maternal experience.
| S-EPMC4099408 | biostudies-literature
Project description:BackgroundPhototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.ObjectivesTo assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.Search methodsSearches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.Selection criteriaWe included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.Data collection and analysisThree review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.Main resultsWe included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
| S-EPMC9979775 | biostudies-literature
Project description:BackgroundLeading authorities in North America recommend universal screening via total serum bilirubin (TSB) measurement or transcutaneous bilirubinometry (TcB) for kernicterus prevention. We assessed costs associated with these 2 screening methods in hospital and in urban and rural community settings.MethodsOur tertiary care centre in Saskatoon, with about 5600 births per year, serves the local population of 300 000; in addition, 30% of patients are referred from outside the local community and surrounding area. We obtained health administrative data for two 6-month periods: before (June 1 to Nov. 30, 2015 [TSB program]) and after (June 1 to Nov. 30, 2016 [TcB-TSB program]) implementation of universal screening with TcB. Data on nurses' time and mileage were collected to assess the mean time for screening and sample transportation. We performed a cost-minimization analysis.ResultsThe observed requirement for TSB blood draws decreased by 71.4% after implementation of TcB (1383.2/1000 live births to 397.8/1000 live births), whereas the overall number of screens increased from 1383.2 to 2758.6/1000 live births. The mean time per screen decreased from 12.52 (95% confidence interval [CI] 10.44-14.59) minutes with TSB to 2.94 (95% CI 2.55-3.33) minutes with TcB (p < 0.001). The estimated cost per TcB screen in hospital and community (urban and rural) settings was $3.54 and $3.76, respectively, and the estimated cost per TSB screen in hospital and in urban and rural community settings was $15.82, $50.21 and $65.03, respectively. The estimated overall 6-month savings with the TcB-TSB hospital and community programs were $19 760 and $6417, respectively.InterpretationThe TcB-TSB program reduced nurses' time to screen and provided immediate results at the point of care. Transcutaneous bilirubinometry reduced the requirement for painful heel pokes while improving access to screening and decreasing the overall program cost.
| S-EPMC6182126 | biostudies-literature
Project description:The present study was performed to elucidate why the photochemical reaction of (ZZ)-bilirubin bound to human serum albumin is singularly selective, and only one of the two (EZ)- and (ZE)-bilirubins, the (ZE)-isomer, is produced. In a kinetic study of the photochemical reaction in vitro, the sum of the relative rate constants of photochemical transformation of (EZ)-bilirubin into both (EZ)-cyclobilirubin and (ZZ)-bilirubin, with a significant preference for the former, was proved to be considerably larger than that of the transformation of (ZZ)-bilirubin into (EZ)-bilirubin. Therefore only one of the geometrical isomers, namely (ZE)-bilirubin, is apparently formed. It was concluded that (EZ)-bilirubin photochemically undergoes (EZ)-cyclization, i.e. structural photoisomerization, while bound to its high-affinity site on human serum albumin, and is an intermediate in the transformation of (ZZ)-bilirubin into (EZ)-cyclobilirubin.
| S-EPMC1144699 | biostudies-other
Project description:Our objective was to analyze the relationship between transcutaneous bilirubin (TcB) measured on an unexposed area of skin and total serum bilirubin (TSB) in preterm infants before, during, and after phototherapy (PT). For this purpose paired TSB and TcB levels were measured daily during the first ten days after birth in preterm infants of less than 32 weeks' gestation. TcB was measured with a Dräger Jaundice Meter JM-103 on the covered hipbone. Agreement between TSB and TcB levels was assessed before, during, and after PT. True negative and corresponding false negative percentages were calculated using different TcB cut-off levels. Data are presented as mean (±SD). We obtained 856 paired TcB and TSB levels in 109 preterm infants (66 boys, gestational age 29.4 ± 1.6 weeks and birth weight 1282 g ± 316 g). We found that the difference between TSB and TcB before PT was significantly lower, 44 (±36) μmol/L, than the difference during and after PT, 61 (±29) μmol/L and 63 (±25) μmol/L, respectively; P < 0.01. Blood sampling could be reduced by 42%, with 2% false negatives, when 50 μmol/L was added to the TcB level at 70% of the PT threshold. Our conclusion is that phototherapy enhances underestimation of TSB by TcB in preterms, even if measured on unexposed skin. The use of specific TcB cut-off levels substantially reduces the need for TSB measurements.
| S-EPMC6568417 | biostudies-literature
Project description:The kinetics for the quantitatively important reaction: (Formula: see text) that is, the photochemical interconversion between bilirubin and its geometric and structural photoisomers bound to human serum albumin in aqueous solution when various wavelengths of monochromatic light were used, were assayed by h.p.l.c. In order to clarify the wavelength-dependence of the relative rate constants in the individual steps, a light-source with a half-bandwidth of 10 nm was used at increments of 20 nm, in the range from 410 nm to 550 nm. We describe for the first time studies on the wavelength-dependence of rate constants in geometric and structural photoisomerization reactions in vitro of (ZZ)-bilirubin or (EZ)-bilirubin bound to human serum albumin, especially the relative rate constants of cyclization of (EZ)-bilirubin into (EZ)-cyclobilirubin. Because studies in vitro have demonstrated that the wavelengths from 350 to 450 nm are mutagenic, the results obtained indicated that the safest and ideal light-source for phototherapy is green light of 510 nm, which keeps (ZE)-bilirubin concentrations as low as possible, as shown by a maximal value of k2 at 510 nm and a relatively low value of k1 at 510 nm. This light-source still ensures the substantial absorption of (ZZ)-bilirubin, which is the precursor of (EZ)-bilirubin, the intermediate in (EZ)-cyclobilirubin formation and, furthermore, as shown by the maximal value of k5 and a considerable value of k4 at 510 nm, promotes the cyclization of (EZ)-bilirubin derived from (ZZ)-bilirubin even though k3 at 510 nm also shows a peak value.
| S-EPMC1146781 | biostudies-other
Project description:Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum.
| S-EPMC4914990 | biostudies-literature
Project description:Lumirubin is the most prevalently excreted hydrophilic bilirubin photoisomer in phototherapy for neonatal jaundice caused by excess hydrophobic unconjugated bilirubin (ZZ-bilirubin). We developed a simple method to estimate the amount of lumirubin by monitoring the reverse photoisomerization of lumirubin to ZZ-bilirubin. Although lumirubin formation was long considered irreversible, exposure to blue light in the presence of the fluorescent protein UnaG, which binds specifically and tightly to ZZ-bilirubin, enables the reverse photoisomerization of lumirubin. This reaction was first detected using a fluorescence assay of neonatal urine sampled during phototherapy and purified lumirubin. The phenomenon of reverse photoisomerization of lumirubin was validated using liquid chromatography-mass spectrometry, which confirmed that lumirubin is reconverted to ZZ-bilirubin in the presence of UnaG. Analyses of 20 urine samples from 17 neonates revealed a significant correlation (correlation coefficient [r] = 0.978; 95% confidence interval 0.867-0.979; P < .001) between lumirubin and ZZ-bilirubin concentration before and after reverse photoisomerization. In general, the rate of photo-reconversion of lumirubin to ZZ-bilirubin is approximately 40%. In conclusion, we demonstrate here that lumirubin can be photo-reconverted to ZZ-bilirubin via exposure to blue light in the presence of UnaG. Utilizing this approach, urinary lumirubin levels can be estimated using an easy-to-perform fluorescence assay.
| S-EPMC9276810 | biostudies-literature
Project description:BackgroundNeonatal jaundice is a common condition occurring in 60%-80% of all healthy-term and late-preterm neonates. In the majority of cases, neonatal jaundice resolves spontaneously and causes no harm; however, in some neonates, significant hyperbilirubinemia can develop and lead to kernicterus jaundice, a serious neurological disease. Phototherapy (PT) is the preferred treatment for jaundice; however, to be effective, PT devices need to have a broad light emission surface to generate no or little heat and to provide an optimal wavelength and light intensity (420-490 nm and ≥30 µW/cm²/nm, respectively).ObjectiveThis study aimed to investigate the feasibility, safety, and level of satisfaction of parents and health care teams with the BUBOlight device, an innovative alternative to conventional hospital PT, in which luminous textiles have been incorporated in a sleeping bag.MethodsThis interventional, exploratory, simple group, nonrandomized, single-center trial will be conducted at Lille Hospital. In total, 10-15 neonates and their parents will be included to obtain evaluable data from 10 parent-neonate pairs. Neonates weighing more than 2500 g at birth and born with ≥37 weeks of amenorrhea that required PT in accordance with the guidelines of the National Institute For Health and Clinical Excellence will receive one 4-hour session of illumination. Total serum bilirubin and transcutaneous bilirubin levels were obtained at the start and 2 hours after the end of PT. Cutaneous and rectal temperatures, heart rate, and oxygen saturation will be measured at the beginning and during PT. The number of subjects is therefore not calculated on the basis of statistical assumptions. We aim to obtain a minimum proportion of 90% (ie, 9 of 10) of the neonates included, who have been able to undergo 4-hour PT without unacceptable and unexpected toxicities. We will calculate the mean, median, quartiles, minimum and maximum values of the quantitative parameters, and the frequency of the qualitative parameters. The rate of patients with no unacceptable and unexpected toxicities (ie, the primary endpoint) will be calculated.ResultsThe first patient is expected to be enrolled at the end of 2020, and clinical investigations are intended for up to June 2021. The final results of this study are expected to be available at the end of 2021.ConclusionsOur findings will provide insights into the safety and feasibility of a new PT device based on light-emitting fabrics for the treatment of newborn jaundice. This new system, if proven effective, will improve the humanization of neonatal care and help avoid mother-child separation.Trial registrationClinicalTrials.gov NCT04365998; https://clinicaltrials.gov/ct2/show/NCT04365998.International registered report identifier (irrid)PRR1-10.2196/24808.
| S-EPMC8188309 | biostudies-literature
Project description:Bilirubin (BR) is the main end-product of the hemoglobin catabolism. For decades, its photophysics has been mainly discussed in terms of ultrafast deactivation of the excited state in solution, where, indeed, BR shows a very low green emission quantum yield (EQY), 0.03%, resulting from an efficient nonradiative isomerization process. Herein, we present, for the first time, unique and exceptional photophysical properties of solid-state BR, which amend by changing the type of crystal, from a closely packed α crystal to an amorphous loosely packed β crystal. BR α crystals show a very bright red emission with an EQY of ca. 24%, whereas β crystals present, in addition, a low green EQY of ca. 0.5%. By combining density functional theory (DFT) calculations and time-resolved emission spectroscopy, we trace back this dual emission to the presence of two types of BR molecules in the crystal: a "stiff" monomer, M1, distorted by particularly strong internal H-bonds and a "floppy" monomer, M2, having a structure close to that of BR in solution. We assign the red strong emission of BR crystals to M1 present in both the α and β crystals, while the low green emission, only present in the amorphous (β) crystal, is interpreted as M2 emission. Efficient energy-transfer processes from M2 to M1 in the closely packed α crystal are invoked to explain the absence of the green component in its emission spectrum. Interestingly, these unique photophysical properties of BR remain in polar solvents such as water. Based on these unprecedented findings, we propose a new model for the phototherapy scheme of BR inside the human body and highlight the usefulness of BR as a strong biological fluorescent probe.
| S-EPMC8389986 | biostudies-literature