Exclusively breastmilk‐fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

Background: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. Objectives: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively. Patients/Methods: Prospective, multi-center, observational study in preterm infants born <33 weeks’ gestation. Blood samples and dietary history were collected before hospital discharge, and post discharge at 2-3 months corrected age. Outcome measures were serum VK1, PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants post-discharge. Results: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies. Conclusions: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency

Effect of a binge-like dosing regimen of methamphetamine on dopamine levels and tyrosine hydroxylase expressing neurons in the rat brain.

Methamphetamine, an amphetamine derivative, is a powerful psychomotor stimulant and commonly used drug of abuse. This study examined the effect of binge-like methamphetamine (MA) dosing (4 × 4 mg/kg, s.c., 2 h apart) on regional dopamine and dopaminergic metabolite levels in rat brain at a range of early time points after final dose (2-48 h). Body temperature was elevated when measured 2 h after the last dose. MA increased dopamine levels in the frontal cortex 2 and 24 h after the last dose. The dopamine level was also increased in the amygdala at 24 h. No change was observed in the striatum at any time point, but levels of the dopamine metabolite DOPAC were markedly reduced at 24 and 48 h. Tyrosine hydroxylase expression is induced downstream of dopamine activity, and it is the rate limiting enzyme in dopamine synthesis. The effect of MA binge-like dosing on the volume of tyrosine hydroxylase containing cell bodies and the area fraction of tyrosine hydroxylase containing fibres was also assessed. MA increased the area fraction of tyrosine hydroxylase fibres in the frontal cortex and reduced the volume of tyrosine hydroxylase containing cell bodies 2 h after last dose in the ventral tegmental area and the substantia nigra. An increase in cell body volume in the substantia nigra was observed 48 h after treatment. These findings collectively highlight the importance of the dopaminergic system in methamphetamine induced effects, identify the frontal cortex, amygdala and striatum as key regions that undergo early changes in response to binge-like methamphetamine dosing and provide evidence of time-dependent effects on the cell bodies and fibres of tyrosine hydroxylase expressing neurons

Effect of a binge-like dosing regimen of methamphetamine on dopamine levels and tyrosine hydroxylase expressing neurons in the rat brain.

Methamphetamine, an amphetamine derivative, is a powerful psychomotor stimulant and commonly used drug of abuse. This study examined the effect of binge-like methamphetamine (MA) dosing (4 × 4 mg/kg, s.c., 2 h apart) on regional dopamine and dopaminergic metabolite levels in rat brain at a range of early time points after final dose (2-48 h). Body temperature was elevated when measured 2 h after the last dose. MA increased dopamine levels in the frontal cortex 2 and 24 h after the last dose. The dopamine level was also increased in the amygdala at 24 h. No change was observed in the striatum at any time point, but levels of the dopamine metabolite DOPAC were markedly reduced at 24 and 48 h. Tyrosine hydroxylase expression is induced downstream of dopamine activity, and it is the rate limiting enzyme in dopamine synthesis. The effect of MA binge-like dosing on the volume of tyrosine hydroxylase containing cell bodies and the area fraction of tyrosine hydroxylase containing fibres was also assessed. MA increased the area fraction of tyrosine hydroxylase fibres in the frontal cortex and reduced the volume of tyrosine hydroxylase containing cell bodies 2 h after last dose in the ventral tegmental area and the substantia nigra. An increase in cell body volume in the substantia nigra was observed 48 h after treatment. These findings collectively highlight the importance of the dopaminergic system in methamphetamine induced effects, identify the frontal cortex, amygdala and striatum as key regions that undergo early changes in response to binge-like methamphetamine dosing and provide evidence of time-dependent effects on the cell bodies and fibres of tyrosine hydroxylase expressing neurons

Functionality of NGF-protected PC12 cells following exposure to 6-hydroxydopamine

6-Hydroxydopamine (6-OHDA) is often used in models of Parkinson’s disease since it can selectively target and kill dopaminergic cells of the substantia nigra. In this study, pre-treatment of PC12 cells with nerve growth factor (NGF) inhibited apoptosis and necrosis by 6-OHDA, including caspase activity and lactate dehydrogenase release. Notably, cells exposed to 6-OHDA in the presence of NGF were subsequently capable of proliferation (when replated without NGF), or neurite outgrowth (with continued presence of NGF). Following 7 days growth in the presence of NGF, expression of bIII tubulin and tyrosine hydroxylase and increased intracellular catecholamines was detectable in PC12 cells, features characteristic of functional dopaminergic neurons. NGF-pre-treated PC12 cells retained expression of bIII-tubulin and tyrosine hydroxylase, but not catecholamine content following 6-OHDA exposure. These data indicate that NGF-protected cells maintained some aspects of functionality and were subsequently capable of proliferation or differentiation. Ó 2006 Elsevier Inc. All rights reserved

Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively. PATIENTS/METHODS: Prospective, multi-center, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and post discharge at 2-3 months corrected age. Outcome measures were serum VK1 , PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants post-discharge. RESULTS: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency