William Diehl-Jones

Nutritional modulation of neonatal outcomes.

In humans, growth and development continues until early adulthood when bone, muscle, and nervous tissue reaches final stages of maturity. Adequate levels of nutritional intake and utilization are critical to optimize ongoing growth. The goal of nutritional therapy for premature or ill neonates has been to provide sufficient nutrients to allow growth to continue at rates seen in utero. Functional immaturity of the gut in the premature infant makes absorption and utilization of nutritional substrates difficult. Premature infants are at risk for developing necrotizing enterocolitis, a potentially lethal bowel disorder. The etiology of necrotizing enterocolitis is not well understood, and a number of theories of causation have been proposed. Breast milk, the optimal source of nutrition for the neonate, is believed to confer some protection against necrotizing enterocolitis. A number of breast milk components have been credited with antiinflammatory properties. Breast milk is recognized for its benefits, yet for preterm infants breast milk alone does not promote adequate growth. A number of breast milk supplements have been investigated to facilitate growth and development and to prevent necrotizing enterocolitis. This article addresses development of the fetal gastrointestinal system, focusing on the biological mediators for normal function and the role of human breast milk and its additives in optimizing neonatal growth. The possible etiologies of necrotizing enterocolitis are discussed in terms of the relationship between this disease and enteral feeding practices.

Antioxidant properties of breast milk in a novel in vitro digestion/enterocyte model.

Objectives: There is good evidence to suggest that human breast milk has antioxidant properties. Our primary goal was to investigate the antioxidant properties of human milk in a combined in vitro digestion/cell culture model that more closely replicates conditions in the gastrointestinal system of the preterm infant. Materials and Methods: An in vitro digestion model was developed that incorporates both gastric and intestinal phases, based on reported luminal pH, digestive enzyme levels, and transit times observed in preterm infants. To mimic the human intestinal mucosa, 2 cell lines—Caco-2BBE and HT29-MTX—were cocultured on Matrigel, an artificial basement membrane substrate. Intracellular oxidative stress was measured with 2 broadly selective oxidant-sensitive dyes, and oxidative DNA damage was assessed by means of single-cell gel electrophoresis. Results: Enterocyte differentiation and mucin secretion were observed by 14 seeding of cultures. Direct exposure to digested milk resulted in a loss of transepithelial electrical resistance; however, exogenous mucin mitigated this loss. Data suggested that both milk and digested milk alleviated oxidative stress in the coculture, and both reduced hydrogen peroxide–induced oxidative DNA damage, as demonstrated by the comet assay. Conclusions: Our results support the hypothesis that breast milk reduces oxidative stress in a cell culture model representative of the intestinal mucosa, and also confirmed the suitability of this combined in vitro digestion/cell culture system for investigating the physiologic effects of enteral nutrients such as breast milk, under conditions similar to those existing in the gastrointestinal system of the preterm infant.

The neonatal liver, Part 1: embryology, anatomy, and physiology.

The liver is the largest organ in the body and is critical to a number of metabolic, regulatory, and detoxification processes. These include the production of bile, metabolic processing of nutrients, synthesis and regulation of plasma proteins and glucose, and biotransformation of drugs and toxins.

In vitro exposure of a novel polyesterurethane graft to enzymes: a study of the biostability of the Vascugraft® arterial prosthesis

The biostability of the Vascugraft arterial prosthesis, a porous synthetic graft made by a novel spinning process from a unique poly(ester urethane) polymer, has been studied by means of an in vitro enzyme incubation technique. Samples of the Vascugraft were exposed to buffered solutions of collagenase and pancreatin, as well as the buffer solutions alone, for periods of up to 100 days at 37 +/- 1 degrees C. On removal and after cleaning, a number of different analytic methods, including X-ray photoelectron spectroscopy for chemical analysis (ESCA), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), size exclusion chromatography (SEC), scanning electron microscopy (SEM), interference microscopy, moisture content and contact angle measurements, were used to examine the changes in chemical structure and surface morphology of the samples. During incubation in both enzymes the molecular weight of the polyurethane appeared to decrease in the presence of enzyme but increase in the presence of buffer. Further microphase separation in the polyurethane material developed during incubation in buffer solutions. Such changes in microstructure were associated with increased surface hydrophilicity, increased moisture content and a significant improvement in the extent of order and preferred orientation of the hard segment domains within the fibres. In the sampling depth of about 5 nm, both enzymes decreased the carbonate group content at the surface of the prosthesis to as little as 40% of their original values. The results from ATR-FTIR and DSC demonstrated that this phenomenon was limited primarily to the soft segment phase. While the Vascugraft prosthesis did exhibit some limited chemical modifications on exposure to concentrated enzyme solutions, nevertheless such changes were confined to the surface layer of the polyurethane microfibres. The importance and significance of those results will be more adequately determined by in vivo investigation.

Nurse cell-oocyte interaction in the telotrophic ovary

Abstract The ultrastructural, immunocytochemical and electrophysiological aspects of the telotrophic ovariole are reviewed, using Rhodnius prolixus as the example. During embryonic development, multiple germ cells become established within each of the 7 ovarioles per ovary. The structural and functional polarity develops during post-embryonic development, resulting in the cytoskeletal-rich adult ovariole. Attention is focused on the cytoskeletal aspects, including microtubules, molecular motors and actin organization. Extracellular electric currents have been mapped using a 2-D vibrating probe. Experiments combining vibrating probe measurements with ion substitutions, channel blockers and inhibitors reveal that sodium and calcium ions are of particular importance. Sodium plays a role in the endocytic pathway essential to vitellogenesis. Calcium appears important to the currents around the tropharium and especially to transient currents at the apical area of the T oocyte. These appear to be associated with closure of the trophic cord. Currents around the T-1 oocyte reverse when the T oocyte loses connection to the tropharium, suggesting the currents may play a significant role in intra-ovariole regulation. Negatively charged and neutral microinjected beads are transported from the tropharium to the oocytes. The value of the telotrophic system to further study cytoplasmic transport and oogenesis is highlighted.

Retinopathy of Prematurity

This article briefly reviews the history of ROP followed by a discussion of the pathogenesis of this complex disorder. We describe the International Classification System for ROP and identify risk factors and screening recommendations. Finally, we discuss some of the measures that have been used in an attempt to both prevent and treat ROP.

The neonatal liver part II: Assessment and diagnosis of liver dysfunction.

The liver, the largest organ in the body, performs many essential functions, including the storage and filtration of blood, production of bile, regulation of plasma proteins and glucose, and biotransformation of drugs and toxins. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. Primary liver disease in neonates is rare; much of the liver dysfunction seen in the neonatal period is secondary to systemic illness such as sepsis or hypoxic injury. It is important for the clinician to have the skills and knowledge necessary to distinguish intrinsic liver disease from liver dysfunction resulting from extrahepatic causes. Early intervention to address the cause of dysfunction is critical to successful management of liver disease. This article reviews the assessment of liver function in neonates and examines the techniques used to diagnose liver dysfunction.

Pathogenesis and Prevention of Chronic Lung Disease in the Neonate

Often used interchangeably, chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) develops primarily in extremely low birth weight infants weighing <1000 g who receive prolonged oxygen therapy and or positive pressure ventilation. CLD, which occurs in as many as 30 percent of infants born weighing <1000 g, contributes significantly to the morbidity and mortality seen in very low birth weight infants. Despite extensive research aimed at identifying risk factors and devising preventative therapies, many questions about the etiology and pathogenesis of BPD remain. This article reviews the embryologic development of the lung and the pathogenesis of CLD or BPD. The authors discuss some of the measures that have been used in an attempt to both prevent and treat BPD.

The neonatal liver: Part III: Pathophysiology of liver dysfunction.

The liver, the largest organ in the body, is critical to a number of key metabolic functions. It also plays an important role in removing the waste products of metabolism (particularly ammonia) and in detoxifying drugs and other substances such as endogenous hormones and steroid compounds. In addition, the liver plays a major role in the production of clotting factors, plasma proteins, bile salts, and bilirubin. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. These often occur secondary to systemic illness, such as sepsis or hypoxic injury, or following the use of drugs or parenteral nutrition to treat other problems. Although rare, primary liver disease does occur in neonates and must be recognized promptly, with treatment initiated in a timely manner to prevent unnecessary sequelae. This article, the third in a series on the liver, examines causes of liver dysfunction in neonates, beginning with an overview of jaundice and hepatomegaly and moving to a discussion of specific diseases.

Myocardin regulates mitochondrial calcium homeostasis and prevents permeability transition

Myocardin is a transcriptional co-activator required for cardiovascular development, but also promotes cardiomyocyte survival through an unclear molecular mechanism. Mitochondrial permeability transition is implicated in necrosis, while pore closure is required for mitochondrial maturation during cardiac development. We show that loss of myocardin function leads to subendocardial necrosis at E9.5, concurrent with elevated expression of the death gene Nix. Mechanistically, we demonstrate that myocardin knockdown reduces microRNA-133a levels to allow Nix accumulation, leading to mitochondrial permeability transition, reduced mitochondrial respiration, and necrosis. Myocardin knockdown elicits calcium release from the endo/sarcoplasmic reticulum with mitochondrial calcium accumulation, while restoration of microRNA-133a function, or knockdown of Nix rescues calcium perturbations. We observed reduced myocardin and elevated Nix expression within the infarct border-zone following coronary ligation. These findings identify a myocardin-regulated pathway that maintains calcium homeostasis and mitochondrial function during development, and is attenuated during ischemic heart disease. Given the diverse role of Nix and microRNA-133a, these findings may have broader implications to metabolic disease and cancer.