Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeine, theophylline, theobromine, and paraxanthine administered to animals and humans distribute in all body fluids and cross all biological membranes. They do not accumulate in organs or tissues and are extensively metabolized by the liver, with less than 2% of caffeine administered excreted unchanged in human urine. Dose-independent and dose-dependent pharmacokinetics of caffeine and other dimethylxanthines may be observed and explained by saturation of metabolic pathways and impaired elimination due to the immaturity of hepatic enzyme and liver diseases. While gender and menstrual cycle have little effect on their elimination, decreased clearance is seen in women using oral contraceptives and during pregnancy. Obesity, physical exercise, diseases, and particularly smoking and the interactions of drugs affect their elimination owing to either stimulation or inhibition of CYP1A2. Their metabolic pathways exhibit important quantitative and qualitative differences in animal species and man. Chronic ingestion or restriction of caffeine intake in man has a small effect on their disposition, but dietary constituents, including broccoli and herbal tea, as well as alcohol were shown to modify their plasma pharmacokinetics. Using molar ratios of metabolites in plasma and/or urine, phenotyping of various enzyme activities, such as cytochrome monooxygenases, N-acetylation, 8-hydroxylation, and xanthine oxidase, has become a valuable tool to identify polymorphisms and to understand individual variations and potential associations with health risks in epidemiological surveys.
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PMID:Pharmacokinetics and metabolism of natural methylxanthines in animal and man. 2085 93

Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A(1) and A(2). Recent evidences suggest that A(2A) receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.
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PMID:Apnea of prematurity: pathogenesis and management strategies. 2112 67

The kidney plays a central role in the clearance of drugs. However, renal drug handling entails more than glomerular filtration and includes tubular excretion and reabsorption, and intracellular metabolization by cellular enzyme systems, such as the Cytochrome P450 isoenzymes. All these processes show maturation from birth onwards, which is one of the reasons why drug dosing in children is not simply similar to dosing in small adults. As kidney development normally finishes around the 36th week of gestation, being born prematurely will result in even more immature renal drug handling. Environmental effects, such as extra-uterine growth restriction, sepsis, asphyxia, or drug treatments like caffeine, aminoglycosides, or non-steroidal anti-inflammatory drugs, may further hamper drug handling in the kidney. Dosing in preterm neonates is therefore dependent on many factors that need to be taken into account. Drug treatment may significantly hamper postnatal kidney development in preterm neonates, just like renal immaturity has an impact on drug handling. The restricted kidney development results in a lower number of nephrons that may have several long-term sequelae, such as hypertension, albuminuria, and renal failure. This review focuses on the interplay between drugs and the kidney in premature neonates.
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PMID:The interplay between drugs and the kidney in premature neonates. 2421 83

Caffeine, standard treatment for apnea of prematurity, improves brainstem auditory processing. We hypothesized that caffeine also improves cortical differentiation of complex speech sounds. We used event-related potential methodology to measure responses to speech-sound contrasts in 45 intensive care neonates, stratified by cumulative exposure as no-, low-, and high-caffeine groups. Sound differentiation in the low-caffeine group and near-term no-caffeine infants was similar with repeated measures analysis of variance controlling for gestational and postnatal age. However, a generalized estimating equation approach demonstrated that, at equivalent postnatal age, differentiation was reduced in the high-caffeine (gestational age 25 weeks) compared to the low-caffeine group (gestational age 28 weeks), reflecting the importance of maturity at birth (Z = 2.77, P < .006). We conclude that caffeine improves measures of auditory processing associated with improved neurodevelopmental outcomes in preterm infants. However, current usage of caffeine for apnea of prematurity cannot fully compensate for the effects of brain immaturity on speech sound processing.
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PMID:Effects of caffeine treatment for apnea of prematurity on cortical speech-sound differentiation in preterm infants. 2493 76

Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment-two-dimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSC-derived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECM promoted increased expression of calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC-derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease.
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PMID:Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. 2739 82

Retinopathy of Prematurity (ROP) is a preventable neovascular retinal disease with a lifetime impact on vision and ocular morbidities. Retinal vessel immaturity and oxygen therapy, influenced or modulated by several risk factors including oxidative stress, intermittent hypoxia and desaturations, inflammation, infection, malnutrition, retinal growth factor deficiencies or excesses, and others are determinant factors of pathologic retinal angiogenesis and ROP. These factors are pharmacologic targets for prevention and/or rescue therapy. These drugs, include intravitreal anti-vascular endothelial growth factor drugs, erythropoietin, ocular propranolol, caffeine, antioxidants, insulin-like growth factor-I, and omega 3 poly-unsaturated fatty acids, and are promising therapies to prevent ROP, but require further studies. Topical ocular non-steroidal anti-inflammatory drugs (NSAIDs) target inflammatory cascade but the best, safest, and most effective ocular NSAID and formulation remain to be developed. Timing of drug intervention appears critical. Moreover, the complex interactions of the various pathophysiologic mechanisms resulting in aberrant angiogenesis thence ROP strongly suggest that drug combinations and synergisms may be required for effective prevention of ROP and a lifetime of blindness.
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PMID:Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity. 3115 20

Bronchopulmonary dysplasia (BPD) is among the most severe complications of very premature birth. Clinical and laboratory studies indicate that lung immaturity, inflammatory lung injury, and disordered lung repair are the primary mechanisms responsible for the development of BPD. Caffeine, initiated within the first 10 days after birth, is one of few drug therapies shown to significantly decrease the risk of BPD in very low birth weight infants. This benefit is likely derived, at least in part, from reduced exposure to positive airway pressure and supplemental oxygen with caffeine therapy. Additional cardiorespiratory benefits of caffeine that may contribute to the lower risk of BPD include less frequent treatment for a PDA, improved pulmonary mechanics, and direct effects on pulmonary inflammation, alveolarization, and angiogenesis. Routine administration of caffeine is indicated in the vast majority of very low birth weight infants. However, current preventative strategies including widespread use of caffeine do not avert BPD in all cases. As such, there is continued need for novel methods to further reduce the risk of BPD in very low birth weight infants.
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PMID:What is bronchopulmonary dysplasia and does caffeine prevent it? 3316 65


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