Correction: Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis (original) (raw)
Related papers
PloS one, 2017
A host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis. In this context, the aim of our study was to characterize the activity of TNAP on Toll-like receptor (TLR) agonists and assess the concentrations of plasma ALP during late-onset sepsis in preterm newborns. Recombinant human TNAP was incubated with microbial products and phosphate release was measured by malachite green assay. Plasma ALP activity was measured serially in a cohort of preterm (N = 129) infants at high risk of late-onset s...
Ontogeny of alkaline phosphatase activity in infant intestines and breast milk
BMC Pediatrics
Background: Necrotizing enterocolitis (NEC) is a devastating disease of intestinal inflammation that primarily affects premature infants. A potential risk factor for necrotizing enterocolitis is exposure of the premature neonatal intestine to environmental bacteria and their proinflammatory products such as lipopolysaccharide. The metalloenzyme alkaline phosphatase (ALP) has been shown to reduce lipopolysaccharide-mediated inflammation. Additionally, premature rat pups have reduced alkaline phosphatase activity and expression as compared to full term pups. To explore the possibility that the human premature neonatal intestine has a paucity of alkaline phosphatase activity, we measured endogenously produced intestinal alkaline phosphatase activity in meconium as a function of gestational age. To test whether breast milk could serve as a source of exogenous alkaline phosphatase to the neonatal intestine through ingestion, we measured alkaline phosphatase activity in breast milk across a range of time points post-birth. Methods: Alkaline phosphatase activity was quantified in 122 meconium samples from infants of gestational ages ranging from 24 to 40 weeks and in 289 breast milk samples collected from 78 individual mothers between days 2-49 post-birth. Results: We observed a strong positive correlation between the meconium alkaline phosphatase activity and gestational age, with preterm infants having lower meconium alkaline phosphatase activities than early term or term infants. Breast milk alkaline phosphatase activity was highest in the first week post-birth, with peak alkaline phosphatase activity at day 2 post-birth, followed by relatively low alkaline phosphatase activity in weeks 2-7. Conclusions: Our results are consistent with the two major risk factors for necrotizing enterocolitis development, preterm birth and lack of breast milk feeding, both contributing to a paucity of alkaline phosphatase activity and impaired capacity to detoxify proinflammatory bacterial products such as lipopolysaccharide.
Neonatal Sepsis: Current Issues
Neonatal sepsis is an entity of worldwide concern. It is peculiar in that it is not a circumscribed disease. It is a scourge both in developed and developing countries as it has been recognised as one of the greatest causes of perinatal mortality. In 2005, it was estimated that about 1.6 million neonatal deaths in developing countries were caused by neonatal infections[1]. In these countries, neonatal infections were found to cause 34 out of 1000 deaths compared to 5 out of 1000 neonatal deaths in developed countries[2]. It was found to be the sixth greatest cause of death neonates in the United States in 2011[3]. Among major causes of neonatal death are perinatal asphyxia and prematurity[1]. Despite decades of history on the subject, a definition has yet to be established for neonatal sepsis. Over the years, the definition has included the isolation of a causative microorganism (bacteria, fungi, virus) from clinical samples obtained from the baby. Loosely, it is a term used to designate a systemic condition of bacterial, viral, or fungal (yeast) origin that is associated with haemodynamic changes and other clinical manifestations and results in substantial morbidity and mortality[4]. In 2005, the International Paediatric Sepsis Consensus Conference defined sepsis as a “systemic inflammatory response syndrome (SIRS) in the presence of or as a result of suspected or proven 5infection.”[5] New born infants are predisposed to infections which lead to sepsis and the reason for this is discernible in the nature of their immune systems. The immune system of the new born is greatly devoid of several components and those which are present are largely underdeveloped[3]. This state leaves them susceptible/vulnerable to infections by a host of organisms which range from viruses, fungi, bacteria et cetera[3].
New use of alkaline phosphatase in neonatology
Romanian Journal of Medical Practice
Background. Alkaline phosphatase is an enzyme that catalyzes the hydrolysis of esters in an alkaline environment. Four isoenzymes have been identified in the human body: placental alkaline phosphatase (PLALP isoenzyme), intestinal alkaline phosphatase (IAP), hepatic/bone/renal alkaline phosphatase (L/B/K ALP) and germ cell alkaline phosphatase (GCALP). The uses of ALP in neonatology have been intensively studied, and associations have been demonstrated between elevated alkaline phosphatase levels and hypocalcemia and hypophosphatemia in premature infants, the onset of early osteopenia and the occurrence of necrotizing enterocolitis. Objective. The current study aimed to demonstrate the correlation between elevated alkaline phosphatase levels in blood from the umbilical cord and elevated transcutaneous bilirubin levels that indicated phototherapy. Material and methods. The study included 250 term newborns within 01-06.2018 and 31 had indication for phototherapy, and 219 without indication for phototherapy, in a tertiary maternity hospital in Bucharest, Romania. Alkaline phosphatase was determined in the umbilical cord serum. Results. The values of the alkaline phosphatase were from 145 to 417 U/l for the newborns without phototherapy and the treated group was beetween 320 and 602 U/l. The values of the alkaline phosphatase were not influenced by the birth weight, Apgar score, and gender. Conclusions. Alkaline phosphatase may represent a predictive marker for the need for phototherapy in term neonates, but further extended studies are required on larger groups of patients.
Early-onset neonatal sepsis and risk factors in the preterm infants
Perinatal Journal
Preterm bebeklerde erken bafllang›çl› sepsis ve risk faktörleri Amaç: Çal›flman›n amac›, preterm yenido¤an bebeklerde erken bafllang›çl› sepsise yol açan risk faktörlerini ve bakteriyel mikro-organizmalar› tespit etmekti. Yöntem: Aç›k uçlu çal›flma, Ocak-Aral›k 2015 tarihleri aras›nda Podgorica, Karada¤'daki Üniversite Klinik Merkezi, Çocuk Has-tal›klar› Enstitüsü, Neonatoloji Merkezi'nde prospektif olarak yürütüldü. Bulgular: Çal›flmaya baflvuran 653 bebekten (427 miad, 226 preterm), sepsis tan›s› alm›fl 71 bebek (32 sepsisli miad yenido¤an [%7.5] ve 39 sepsisli preterm yenido¤an [%17.3]) çal›flmaya dahil edildi. Sepsisli 44 yenido¤anda kan kültürü sonucu pozitifti (20 miad, 24 preterm). Yirmi dört preterm bebekten, erken bafllang›çl› sepsis 8 olguda (dominant patojen E. coli) ve geç bafllang›çl› sepsis 16 olguda (dominant patojenler Klebsiella pneumoniae ve Staphylococcus CoN) tespit edildi. Prematüre do¤um ve düflük do¤um a¤›rl›¤›, neonatal sepsis için en yayg›n risk faktörleri olarak belirlendi. Maternal preeklampsi, erken membran rüptürü ve perinatal asfiksi de, preterm yenido¤an bebeklerde erken bafllang›çl› neonatal sepsis için önemli risk faktörleri olarak belirlendi. Sonuç: Verilerimiz, prematüre do¤um ve düflük do¤um a¤›rl›¤›-n›n, maternal preeklampsi, erken membran rüptürü ve perinatal asfiksi ile birlikte sepsis için en yayg›n risk faktörleri oldu¤unu göstermektedir.
Aim: To examine the risk factors and the clinical-bacteriological profile of early sepsis in newborns in the neonatal intensive care unit. Study Design: An observational / descriptive. Place and duration: In the Pediatric Unit II of Services Hospital Lahore for one year duration from March 2019 to March 2020. Material and methods: Relevant data of maternal risk factors was collected by taking history from mothers and consulting their case records. All infants developing clinical signs/symptoms of sepsis within 7 days of birth with positive blood cultures or supported by at least 2 laboratory parameters were diagnosed to have early onset neonatal sepsis (EONS). Data was analyzed by using SPSS version 19. Results: Among 2620 live births, 82 neonates were diagnosed as a case of EONS (Incidence 31.3/1000 live births), female to male ratio was 1:1.5 and maximum numbers of cases were in 0-3 day's age group (54.8%). Majority of cases (60.9%) came from low socioeconomic group. Among neonates with EONS 48.8% & 75.6 were low birth weight and preterm respectively. Culture proven cases were only 17.1%. It is noted that among those who developed EONS 71.9% were neonates considered to be at risk for sepsis due to presence of maternal and neonatal risk factors. Prolonged rupture of membranes and foul smelling liquor were the most significant perinatal risk factors. The most important comorbidities were Hyperbilirubinemia (26.8%), metabolic acidosis (19.5%) & DIC (14.6%). In this study, the mortality rate was 7.3%. Klebsiella pneumoniae and Pseudomonas were the commonest causative organisms found in culture positive cases (42.8%). Conclusion: Information on the detection of risk factors and the clinical and bacteriological profile of EONS can lead to early diagnosis and rapid therapeutic interventions that minimize mortality and morbidity in newborns.
Alkaline Phosphatase as a Treatment of Sepsis-Associated Acute Kidney Injury
Journal of Pharmacology and Experimental Therapeutics, 2013
Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.