Serum caffeine concentrations in preterm infants: a retrospective study.

Therapeutic drug monitoring is generally unnecessary in caffeine treatment for apnea of prematurity, as serum caffeine concentrations in preterm infants are normally markedly lower than those at which caffeine intoxication occurs. However, several studies have reported preterm infants having developed toxicity. This retrospective observational study, conducted at a tertiary center in Kagawa, Japan, aimed to evaluate the correlation between the maintenance dose and serum caffeine concentrations and determine the maintenance dose leading to suggested toxic caffeine levels. We included 24 preterm infants (gestational age, 27 ± 2.9 weeks; body weight, 991 ± 297 g) who were treated with caffeine citrate for apnea of prematurity between 2018 and 2021, and 272 samples were analyzed. Our primary outcome measure was the maintenance dose leading to suggested toxic caffeine levels. We found a positive correlation between caffeine dose and serum caffeine concentrations (p < 0.05, r = 0.72). At doses of ≥ 8 mg/kg/day, 15% (16/109) of patients had serum caffeine concentrations above the suggested toxic levels. Patients who receive doses ≥ 8 mg/kg/day risk reaching the suggested toxic serum caffeine levels. It remains unclear whether suggested toxic caffeine concentrations are detrimental to neurological prognosis. Further investigation is required to understand the clinical effects/outcomes of high serum levels of caffeine and to obtain long-term neurodevelopmental follow-up data.

Quantitative effects of bilirubin structural photoisomers on the measurement of direct bilirubin via the vanadate oxidation method.

BACKGROUND: Exposing blood serum samples to ambient white light-emitting diode (WLED) light may accelerate bilirubin photoisomer production. We previously demonstrated the quantitative effect of bilirubin configurational isomers (BCI) on direct bilirubin (DB) value using the vanadate oxidation method. However, the effects of bilirubin structural photoisomers (BSI) remain unclear. METHODS: In Study 1, the relationship between WLED irradiation time and BSI production was examined. Serum samples from five neonates were irradiated with WLED light for 0, 10, 30, 60 and 180 min. Bilirubin isomer concentration and BSI production rates were calculated. In Study 2, we performed quantitative investigation of BSI effect on DB values: Differences in DB, BCI and BSI values before and after irradiation were calculated as ⊿DB, ⊿BCI and ⊿BSI, respectively. Assuming the coefficient of BCI affecting DB values was 'a', relational expression was ⊿DB = a*⊿BSI + 0.19*⊿BCI. Serum samples from 15 neonates were irradiated with green LED light for 10 and 30 s. The respective bilirubin isomer levels were measured, and the coefficient was derived. RESULTS: In Study 1, the median BSI production rate was 0.022 mg/dL per min in specimens with an unconjugated bilirubin concentration of 10.88 mg/dL. In Study 2, assuming that ⊿DB-0.19*⊿BCI was Y and ⊿BSI was X, the relational expression was Y = 0.34X-0.03 (R2 = 0.87; p < .01) and a = 0.34. CONCLUSIONS: Under ambient WLED light, serum sample generated 1.3 mg/dL BSIs in 1 h. Approximately 34% (0.44 mg/dL) of BSI concentrations was measured as DB when using the vanadate oxidation method according to the above equation.

Cisplatin-induced activation of TGF-ß signaling contributes to drug resistance.

Growing evidence suggests an association between epithelial-mesenchymal transition (EMT), a hallmark of tumor malignancy, and chemoresistance to a number of anti-cancer drugs. However, the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear. To address this issue, we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts. In these clones, the epithelial marker E-cadherin was downregulated, whereas the mesenchymal marker N-cadherin was upregulated. Moreover, the expression of EMT-related transcription factors, including Slug, was elevated. On the other hand, the upregulation of other mesenchymal marker Vimentin was weak, suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones. These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-ß (TGF-ß) receptor kinase inhibitors, indicating that TGF-ß signaling is involved in cisplatin-induced the mesenchymal-like phenotypic changes. Moreover, cisplatin was observed to enhance the secretion of TGF-ß into the culture media without influencing TGF-ß gene transcription. These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-ß secretion, ultimately resulting in drug resistance.

Hybrid molecule between platanic acid and LCL-161 as a yes-associated protein degrader.

Dysregulated yes-associated protein (YAP) is involved in several malignant cancers. However, discovering a druggable YAP inhibitor(s) is difficult because YAP itself does not have any enzymatic activity. In such cases, targeted protein degradation strategies based on hybrid molecules that bind to the target protein and an E3 ubiquitin ligase are useful for suppressing proteins that exhibit aberrant activation and/or excessive expression. Upon screening YAP-interacting small compounds, we identified HK13, a platanic acid, as a novel compound that interacts with YAP. Next, we synthesized hybrid compounds of platanic acid and LCL-161, which reportedly shows a high affinity for cIAP, one of E3 ubiquitin ligases. Among these compounds, HK24 possessed the ability to inhibit the growth of YAP overexpressing NCI-H290 cells. This inhibitory activity may be mediated by YAP degradation, although HK24 exhibited weak YAP degradation. Furthermore, we confirmed involvement of proteasome pathway in HK24-dependent YAP degradation by culturing NCI-H290 cells in the presence of a proteasome inhibitor. Therefore, it is possible that platanic acid is a potential candidate for molecular medicine targeting YAP.

Fetal and neonatal bilirubin metabolism.

Human fetal and neonatal bilirubin metabolism is centered on 4Z,15Z-bilirubin IXα (BR) due to the extremely low BR conjugating capacity of the liver. BR is a unique, highly lipophilic substance with physiological and toxic effects in the cell membranes of organs and body tissues. The fetus excretes BR through the placenta to the maternal circulation. After birth, BR is thought to act as an antioxidant against the increase in reactive oxygen species caused by the rapid increase in oxygen concentration during the adaptation process from in amniotic fluid to in air. However, bilirubin encephalopathy is a toxic effect of bilirubin. Due to the lipophilic nature of BR, it must be bound to a carrier to be distributed to various parts of the body by hydrophilic blood. This carrier of BR is human serum albumin (HSA). In humans, BR can be excreted efficiently after undergoing photochemical reactions upon high affinity binding to HSA. HSA also plays an important role in the prevention of bilirubin encephalopathy. This review focuses on the developmental and physiological role of bilirubin metabolism during the fetal and neonatal periods.

Furosemide clearance in very preterm neonates early in life: A pilot study using scavenged samples.

BACKGROUND: Furosemide is an off-label drug, frequently used as a diuretic in neonates with oliguria and/or edema. Its clearance in preterm neonates is lower than in term neonates or children. We aimed, herein, to clarify furosemide clearance (CL) in very preterm (VP) neonates (<28 weeks' gestation) within the first 2 weeks of life and identify the factors predictive of the pharmacokinetics (PK) parameters, such as CL. METHODS: Furosemide was administered at 0.5 or 1 mg/kg in a 0.5-h infusion via a syringe pump; blood samples were drawn from an artery or vein after the intravenous injection. The serum furosemide concentration was measured using high-performance liquid chromatography. The PK parameters were then analyzed using Bayesian estimation. RESULTS: Thirteen blood samples were obtained from 10 VP neonates after intravenous injection. The mean postconceptional age and mean postnatal days at exposure to furosemide were 26.9 weeks and 7.1 days, respectively. The estimated mean CL was 16.5 mL/kg/h. The mean distribution volume (Vd) and elimination half-life (t1/2) were 0.37 L/kg and 15.3 h, respectively. Furosemide CL was negatively associated with serum creatinine (SCr) [CL = 84.2 - 67.1 × SCr (mg/dL)]. CONCLUSIONS: Very preterm neonates within the first 2 weeks of life had a higher CL than subjects in other preterm neonatal studies. The SCr level was the sole parameter influencing furosemide CL and might serve as a good index for furosemide dosing in VP neonates.

Endothelial-specific depletion of TGF-ß signaling affects lymphatic function.

BACKGROUND: Transforming growth factor (TGF)-ß is a multifunctional cytokine involved in cell differentiation, cell proliferation, and tissue homeostasis. Although TGF-ß signaling is essential for maintaining blood vessel functions, little is known about the role of TGF-ß in lymphatic homeostasis. METHODS: To delineate the role of TGF-ß signaling in lymphatic vessels, TßRIIfl/fl mice were crossed with Prox1-CreERT2 mice to generate TßRIIfl/fl; Prox1-CreERT2 mice. The TßRII gene in the lymphatic endothelial cells (LECs) of the conditional knockout TßRIIiΔLEC mice was selectively deleted using tamoxifen. The effects of TßRII gene deletion on embryonic lymphangiogenesis, postnatal lymphatic structure and drainage function, tumor lymphangiogenesis, and lymphatic tumor metastasis were investigated. RESULTS: Deficiency of LEC-specific TGF-ß signaling in embryos, where lymphangiogenesis is active, caused dorsal edema with dilated lymphatic vessels at E13.5. Postnatal mice in which lymphatic vessels had already been formed displayed dilation and increased bifurcator of lymphatic vessels after tamoxifen administration. Similar dilation was also observed in tumor lymphatic vessels. The drainage of FITC-dextran, which was subcutaneously injected into the soles of the feet of the mice, was reduced in TßRIIiΔLEC mice. Furthermore, Lewis lung carcinoma cells constitutively expressing GFP (LLC-GFP) transplanted into the footpads of the mice showed reduced patellar lymph node metastasis. CONCLUSION: These data suggest that TGF-ß signaling in LECs maintains the structure of lymphatic vessels and lymphatic homeostasis, in addition to promoting tumor lymphatic metastasis. Therefore, suppression of TGF-ß signaling in LECs might be effective in inhibiting cancer metastasis.

A survey of the reactivity of in vitro diagnostic bilirubin reagents developed in Japan using artificially prepared bilirubin materials: A comparison of synthetic delta, unconjugated, and taurine-conjugated bilirubin.

BACKGROUND: In vitro diagnostic bilirubin reagents based on oxidation with bilirubin oxidase or vanadic acid for total and direct-reacting bilirubin are widely used in Japan; however, their reactivity to unconjugated and conjugated bilirubin and delta bilirubin has not been completely disclosed by manufacturers. We used artificially prepared bilirubin materials to investigate the reactivity with four in vitro diagnostic bilirubin reagents. METHODS: Porcine unconjugated bilirubin solution, chemically synthesized ditaurobilirubin solution, and chemically synthesized delta bilirubin solution were used as surrogates of naturally occurring unconjugated bilirubin, conjugated bilirubin, and delta bilirubin, respectively. The total bilirubin and direct-reacting bilirubin concentrations were measured by three bilirubin oxidase methods and one vanadic acid method, and the observed concentrations were compared with those obtained by the diazo-based reference measurement procedure. RESULTS: The unconjugated bilirubin and delta bilirubin concentrations were similar when any of the four in vitro diagnostic bilirubin reagents were used during total bilirubin measurement. This was consistent with reference measurement procedure and exhibited a converged inter-method variation. Compared with reference measurement procedure, significantly low ditaurobilirubin concentrations were observed by the in vitro diagnostic bilirubin reagents despite the converged inter-method variation. In delta bilirubin measurement, some reagents reacted doubtfully with unconjugated bilirubin, while showed lower ditaurobilirubin concentrations than its corresponding total bilirubin concentration. Reactivity with delta bilirubin was different for each method including reference measurement procedure. Some reagents were developed to react less with delta bilirubin and others to strongly react with delta bilirubin. CONCLUSIONS: We revealed the reactivity of IVD-TB and IVD-DB reagents to artificially prepared bilirubin materials, and their consistency with reference measurement procedure. The delta bilirubin data results vary depending on the reagents used.

Involvement of miR-3180-3p and miR-4632-5p in palmitic acid-induced insulin resistance.

Insulin resistance is defined as a failure to trigger the activation of the PI3K-AKT pathway by normal levels of insulin; therefore, it is well linked to metabolic disorders. Although multiple mechanisms contribute to insulin resistance, one major cause is elevated concentrations of plasma free fatty acids, which are known to suppress insulin signaling. However, the underlying mechanism is still elusive. Here, we found that palmitic acid increased the expression of two miRNAs, miR-3180-3p and miR-4632-5p, in HepG2 cells. Transfection of HepG2 cells with miR-3180-3p or miR-4632-5p reduced insulin-induced activation of the PI3K-AKT pathway. Moreover, palmitic acid or two miRNAs inhibited insulin-induced phosphorylation of Tyr612 on IRS-1 without affecting insulin receptor activation. Therefore, two miRNAs are suggested to be involved in palmitic acid-induced insulin resistance through suppression of insulin-induced IRS-1 phosphorylation. Identification of miR-3180-3p and miR-4632-5p targets could provide valuable information for the development of therapeutic drugs for type 2 diabetes.

Characteristics of bilirubin photochemical changes under green light-emitting diodes in humans compared with animal species.

Phototherapy using light-emitting diodes (LEDs) centered on the green spectrum, which has a high cyclobilirubin production rate, was as effective as that centered on the blue spectrum for neonatal hyperbilirubinemia. There are no reports of species differences in bilirubin photochemical changes in this spectrum, and the characteristics of bilirubin photochemical changes in humans must be elucidated to proceed with the development of new light sources that include these spectra. This report describes the characteristic photochemical kinetics of bilirubin under green-spectrum LEDs in human, rat, rabbit, dog, pig, sheep, bovine and chicken serum albumin and rhesus monkey serum. These albumin-bilirubin complex solutions were irradiated by green LEDs, and the time-course changes in bilirubin photoisomers were measured by high-performance liquid chromatography. The cyclobilirubin production rates in humans, pigs, and monkeys were significantly higher than those in other species. The rate constant of (EZ)-cyclobilirubin production from (EZ)-bilirubin 'k' was significantly higher in humans and monkeys than in other species. In conclusion, bilirubin photochemical kinetics under green spectrum LEDs in humans were characterized by a high cyclobilirubin production rate at a low substrate concentration. The bilirubin photochemical kinetics in monkeys were similar to those in humans.

Effects of bilirubin configurational photoisomers on the measurement of direct bilirubin by the vanadate oxidation method.

BACKGROUND: Direct-reacting bilirubin concentrations measured using vanadate chemical oxidation method do not exactly match the conjugated bilirubin concentration. One of the causes is the effect of bilirubin photoisomers. However, the quantitative evaluation of the effects of these photoisomers has not been sufficiently conducted. In particular, the influence of bilirubin configurational isomers on direct bilirubin is the most critical factor. METHODS: Sixteen residual serum samples were used. For quantitative analysis based on the change in direct bilirubin and bilirubin configurational isomer, samples were irradiated via blue light-emitting diodes to suppress the production of bilirubin structural isomers. Total bilirubin and direct bilirubin concentrations were measured using the vanadate chemical oxidation method. Concentrations of 4Z,15Z-bilirubin IXα and its photoisomers were measured using high-performance liquid chromatography. The sum of 4Z,15E-bilirubin IXα and 4E,15Z-bilirubin IXα was notated as bilirubin configurational isomer, and the differences between the measured values of the irradiated and non-irradiated samples were calculated and notated as ΔDB and ΔBCI. RESULTS: In non-irradiated and irradiated samples, total bilirubin and direct bilirubin concentrations were 10.73 mg/dL with significant a decrease to 10.60 mg/dL and 0.69 mg/dL with a significant increase to 0.78 mg/dL, while bilirubin configurational isomer values were 1.00 mg/dL and 1.52 mg/dL, respectively. The linear regression equation revealed a significant positive correlation of Y = 0.187X-0.006 between ΔDB (Y) and ΔBCI (X). CONCLUSION: Applying the vanadate chemical oxidation method affected approximately 19% of the bilirubin configurational isomer concentration for direct bilirubin. Extreme caution is necessary when interpreting the measured values of samples indicative of unconjugated hyperbilirubinaemia.

Narciclasine is a novel YAP inhibitor that disturbs interaction between YAP and TEAD4.

Yes-associated protein (YAP) is involved in development, cell growth, cell size, and homeostasis and plays a key role in the progression of various cancers. Among them, constitutive activation of YAP can often be observed in malignant mesothelioma, which arises in the pleura, peritoneum, and pericardium because of inactivation of the Hippo pathway. To date, however, only less-effective treatments such as chemotherapy, radiation therapy, and surgery are available for patients with malignant mesothelioma. In this study, we identified narciclasine as a novel YAP inhibitor that prevents YAP from interacting with TEAD4 because it competes with TEAD4 for binding to YAP. Furthermore, narciclasine could perturb the cell growth and colony formation of malignant mesothelioma NCI-H290 cells in addition to inhibiting their growth in nude mice. Therefore, narciclasine might be a potential seed for a novel antitumor drug against malignant mesothelioma and other cancers in which hyperactivation and/or overexpression of YAP are observed.

Environmental and soil characteristics in Ephedra habitats of Uzbekistan.

In Uzbekistan, Ephedra distachya L., E. equisetina Bunge, E. foliata Boiss. ex C. A. Mey., E. lomatolepis Schrenk, and E. strobilacea Bunge show species specificity for habitat environments and physical and chemical characteristics of habitat soils. Furthermore, the relationship between soil characteristics and ephedrine and pseudoephedrine contents was examined. E. distachya was found growing from 80 to 200 m above sea level (a.s.l) in the Plateau Ustyurt on the desert steppe of cliffs on soil having relatively higher loss on ignition (19.8-33.8%) and water-soluble cations (Ca2+, 5.14-133.13; Mg2+, 0.85-3.18; and Na+, 2.27-8.33 mmol/100 g dry soil weight) than for other Ephedra habitats. E. strobilacea was found growing on the flat sandy Kyzylkum desert at 94 m a.s.l. and had habitat soil that was the driest with the lowest loss on ignition (2.9%) and highest Na+ (9.05 mmol/100 g dry soil weight) of all the Ephedra habitat soils. On dry steppe from 1054 to 1819 m a.s.l., E. foliata, E. lomatolepis, and E. equisetina formed not only a single community but also a complex community on constantly collapsing sandy gravel slope with relatively higher Ca2+ (3.40-17.44 mmol/100 g dry soil weight) soil content. Notably, E. equisetina grew on the dry steppe of constantly collapsing sandy gravel slopes, in rocky areas, on sandy gravel floodplains of rivers, and on stable humus soil at the base of coniferous trees in a wide range of habitats from dry steppe to coniferous forest zones at altitudes ranging from 1392 to 1819 m a.s.l., as reflected in the greater variability than for other Ephedra habitats in the parameters of loss on ignition (1.4-34.8%), pH (7.1-9.6), NO3- (0.08-35.17 mmol/100 g dry soil weight), Ca2+ (0.24-17.44 mmol/100 g dry soil weight), Mg2+ (not detected-1.25 mmol/100 g dry soil weight), and Na+ (0.13-5.19 mmol/100 g dry soil weight). Ephedrine alkaloids were not detectable in E. strobilacea, E. foliata, and E. lomatolepis. Almost all E. distachya contained only pseudoephedrine (1.25-1.59% of dry weight, %DW), while E. equisetina contained from 1.31 to 2.05%DW ephedrine and from 1.29 to 2.80%DW pseudoephedrine. Ephedrine and pseudoephedrine in E. equisetina showed a statistically significant negative correlation with soil Cl- and Mg2+, respectively.

Smad7 Enhances TGF-ß-Induced Transcription of c-Jun and HDAC6 Promoting Invasion of Prostate Cancer Cells.

Transforming growth factor ß (TGF-ß) enhances migration and invasion of cancer cells, causing life-threatening metastasis. Smad7 expression is induced by TGF-ß to control TGF-ß signaling in a negative feedback manner. Here we report an additional function of Smad7, i.e., to enhance TGF-ß induction of c-Jun and HDAC6 via binding to their regulatory regions, promoting migration and invasion of prostate cancer cells. Lysine 102 in Smad7 is crucial for binding to specific consensus sites in c-Jun and HDAC6, even when endogenous Smad2, 3, and 4 were silenced by siRNA. A correlation between the mRNA expression of Smad7 and HDAC6, Smad7 and c-Jun, and c-Jun and HDAC6 was found in public databases from analyses of prostate cancer tissues. High expression of Smad7, HDAC6, and c-Jun correlated with poor prognosis for patients with prostate cancer. The knowledge that Smad7 can activate transcription of proinvasive genes leading to prostate cancer progression provides clinically relevant information.

Physical and chemical characteristics of soils in Ephedra gerardiana and E. pachyclada habitats of Kali Gandaki Valley in Central Nepal.

In the Kali Gandaki Valley in Central Nepal, Ephedra gerardiana and E. pachyclada show species specificity for physical and chemical characteristics of soils. Here, the relationship between soil characteristics and ephedrine and pseudoephedrine contents was examined. E. gerardiana grew in moist alpine scrub and upper alpine meadow from 3735 to 4156 m a.s.l., while E. pachyclada grew in the lower Caragana steppe and dry alpine scrub from 2629 to 3671 m a.s.l. The soil texture of E. gerardiana and E. pachyclada collection sites were classified as loam or sandy loam mainly composed of sand and silt. Loss on ignition (%) of soil in E. gerardiana habitats (28.4-35.0%) was markedly higher than for that in E. pachyclada habitats (14.2-17.2%). E. pachyclada soil (pH 8.4-9.2) was more alkaline than that for E. gerardiana (pH 8.5). The five ions (Cl-, SO42-, Ca2+, Mg2+, and Na+) in soil of E. pachyclada (Cl-, 0.01-18.97 mmol/100 g dry soil weight; SO42-, 1.95-83.33; Ca2+, 3.79-77.91; Mg2+, 1.28-27.9; Na+, 0.94-34.49) were markedly higher than those of E. gerardiana (Cl-, 0.18-0.29; SO42-, 0.07-0.08; Ca2+, 4.19-4.59; Mg2+, 0.22-0.58; Na+, 0.93-1.40). The main factor contributing to strongly alkali soils for each species was different between E. gerardiana and E. pachyclada: CaCO3 for E. gerardiana and CaSO4, MgSO4, NaCl, or a combination of these for E. pachyclada. The total ephedrine and pseudoephedrine content in E. gerardiana and E. pachyclada ranged from 1.67-1.88%DW and 1.95-4.80%DW, respectively. Both E. gerardiana and E. pachyclada were amenable for use a raw material source for extraction of ephedrine and pseudoephedrine, and the ephedrine content of both species showed a statistically significantly positive correlation with Mg2+ and Na+ contents of the soil.

Dissociation of the AhR/ARNT complex by TGF-ß/Smad signaling represses CYP1A1 gene expression and inhibits benze[a]pyrene-mediated cytotoxicity.

Cytochrome P450 1A1 (CYP1A1) catalyzes the metabolic activation of polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and is transcriptionally regulated by the aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex upon exposure to PAHs. Accordingly, inhibition of CYP1A1 expression reduces production of carcinogens from PAHs. Although transcription of the CYP1A1 gene is known to be repressed by transforming growth factor-ß (TGF-ß), how TGF-ß signaling is involved in the suppression of CYP1A1 gene expression has yet to be clarified. In this study, using mammalian cell lines, along with shRNA-mediated gene silencing, CRISPR/Cas9-based genome editing, and reporter gene and quantitative RT-PCR assays, we found that TGF-ß signaling dissociates the B[a]P-mediated AhR/ARNT heteromeric complex. Among the examined Smads, Smad family member 3 (Smad3) strongly interacted with both AhR and ARNT via its MH2 domain. Moreover, hypoxia-inducible factor 1α (HIF-1α), which is stabilized upon TGF-ß stimulation, also inhibited AhR/ARNT complex formation in the presence of B[a]P. Thus, TGF-ß signaling negatively regulated the transcription of the CYP1A1 gene in at least two different ways. Of note, TGF-ß abrogated DNA damage in B[a]P-exposed cells. We therefore conclude that TGF-ß may protect cells against carcinogenesis because it inhibits CYP1A1-mediated metabolic activation of PAHs as part of its anti-tumorigenic activities.

Hour-specific nomogram for transcutaneous Bilirubin in newborns in Myanmar.

BACKGROUND: Neonatal hyperbilirubinemia is a significant health problem in Myanmar, and the rate of kernicterus is also higher than in developed countries. Non-invasive methods for early detection and treatment of hyperbilirubinemia are urgently needed. In this study, we used transcutaneous bilirubin (TcB) measurements to develop an hour-specific TcB nomogram for the effective management of hyperbilirubinemia in Myanmar newborns. METHODS: The bilirubin levels of neonates born in Central Women Hospital in Yangon, Myanmar were measured three times a day within 72 h after birth using a transcutaneous bilirubinometer. An hour-specific TcB nomogram was created based on the data. RESULTS: Participants were 512 infants (287 boys, 225 girls) born in Central Women's Hospital in Yangon. The mean (±SD) gestational age was 38.4 ± 1.2 weeks; birthweight was 3078 ± 412 g. A total of 3,039 plots were obtained, and the TcB nomogram was created with smoothed percentile curves (97.5th, 50th, and 2.5th percentiles) for 0-72 h after birth. CONCLUSIONS: An hour-specific TcB nomogram was successfully created to manage hyperbilirubinemia in Myanmar newborns.

Developmental changes in urinary coproporphyrin ratio in premature infants.

BACKGROUND: Premature infants have a high concentration of conjugated bilirubin in their blood, although they have a poor glucuronide conjugation of bilirubin. This may be due to developmental changes in the function of adenosine triphosphate binding cassette subfamily C member 2, which is involved in the cellular export of conjugated bilirubin. In the present study, we examined the developmental changes in the urinary coproporphyrin I/(urinary coproporphyrin I+ urinary coproporphyrin III) ratio (UCP (I/ [I + III])), a known biomarker for adenosine triphosphate binding cassette subfamily C member 2 function, in premature infants. METHOD: Twenty-one premature infants born between 25 and 32 weeks of gestation were included in the study. Urine samples were collected within 24 h of birth, and at 1 week and 3-4 weeks after birth. The samples were analyzed by high-performance liquid chromatography to calculate UCP (I/ [I + III]) to examine its association with postnatal age and corrected gestational age. Subjects were excluded if they had liver dysfunction, cholestasis, urinary tract infection, or chromosomal abnormalities. RESULTS: The average UCP (I/ [I + III]) within 24 h of birth, at 1 week, and at 3-4 weeks after birth was 0.84, 0.61, and 0.65, respectively. The UCP (I/ [I + III]) within 24 h of birth was significantly higher than that measured at 1 week or 3-4 weeks after birth. There was no significant correlation between UCP (I/ [I + III]) and the corrected gestational age. CONCLUSION: The UCP (I/ [I + III]) was higher within 24 h of birth. It decreased 1 week after birth and remained low without any significant changes for up to 4 weeks after birth.

Green light-emitting diode phototherapy for neonatal hyperbilirubinemia: Randomized controlled trial.

BACKGROUND: The main photochemical pathway in phototherapy for neonatal hyperbilirubinemia is the production and elimination (in bile or urine) of cyclobilirubin, which is a structural photoisomer of bilirubin, and which is most efficiently produced by green light. Green light-emitting diode (LED) phototherapy, however, has not been evaluated in the clinical setting because it is not recommended in American Academy of Pediatrics guidelines. We therefore compared the efficacy of green LED phototherapy and blue LED phototherapy in patients with neonatal hyperbilirubinemia. METHODS: In this prospective randomized controlled trial, neonates with hyperbilirubinemia were randomly allocated to a green LED or blue LED phototherapy group. Both groups underwent 24 h of phototherapy, and blood was sampled before and after 24 h of phototherapy. Total serum bilirubin (TSB) was measured using enzymatic methods and bilirubin photoisomers were measured on high-performance liquid chromatography. RESULTS: Thirty-four infants were randomized (green, n = 16; blue, n = 18). TSB decreased significantly from 15.3 ± 1.5 to 13.9 ± 1.5 mg/dL in the green LED group (P < 0.01) and from 16.2 ± 1.3 to 14.5 ± 1.7 mg/dL in the blue LED group (P < 0.01) after 24 h of phototherapy. No significant difference was found in TSB reduction after phototherapy between the groups. CONCLUSIONS: Both light sources produced a significant reduction in TSB, indicating clinical effectiveness.