Calcium Chloride in Neonatal Parenteral Nutrition Solutions with and without Added Cysteine: Compatibility Studies Using Laser and Micro-Flow Imaging Methodology.

BACKGROUND: Previous studies of compatibility of calcium chloride (CaCl2) and phosphates have not included particle counts in the range specified by the United States Pharmacopeia. Micro-flow imaging techniques have been shown to be comparable to light obscuration when determining particle count and size in pharmaceutical solutions. OBJECTIVE: The purpose of this study was to do compatibility testing for parenteral nutrition (PN) solutions containing CaCl2 using dynamic light scattering and micro-flow imaging techniques. METHODS: Solutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl2, and sodium phosphate (NaPhos) were compounded with and without cysteine. All solutions contained standard additives to neonatal PN solutions including dextrose, trace metals, and electrolytes. Control solutions contained no calcium or phosphate. Solutions were analyzed for particle size and particle count. Means of Z-average particle size and particle counts of controls were determined. Study solutions were compared to controls and United States Pharmacopeia (USP) Chapter 788 guidelines. The maximum amount of Phos that was compatible in solutions that contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined. Compatibility of these solutions was verified by performing analyses of 5 repeats of these solutions. Microscopic analyses of the repeats were also performed. RESULTS: Amounts of CaCl2 and NaPhos that were compatible in solutions containing 1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that could be added to TrophAmine solutions of > = 2.5% AA containing at least 10 mmol/L of CaCl2 was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount of NaPhos that could be added to solutions containing 10 mmol/L of CaCl2 to 10 mmol/L. CONCLUSION: Calcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus.

Calcium chloride in neonatal parenteral nutrition: compatibility studies using laser methodology.

INTRODUCTION: We have previously reported results of precipitation studies for neonatal parenteral nutrition solutions containing calcium chloride and sodium phosphate using visual methods to determine compatibility. The purpose of this study was to do further testing of compatibility for solutions containing calcium chloride using more sensitive methods. METHODS: Solutions of Trophamine (Braun Medical Inc, Irvine, CA) and Premasol (Baxter Pharmaceuticals, Deerfield, IL) were compounded with calcium chloride and potassium phosphate. Controls contained no calcium or phosphate. After incubation at 37° for 24 hours solutions without visual precipitation were analyzed to determine mean particle size using dynamic light scattering from a laser light source. RESULTS: Particle sizes were similar for control solutions and those without visual precipitation and a mean particle size <1000 nm. Compatible solutions were defined as those with added calcium and phosphate with no visual evidence of precipitation and mean particle size <1000 nm. In solutions containing 2.5-3% amino acids and 10 mmol/L of calcium chloride the maximum amount of potassium phosphate that was compatible was 7.5 mmol/L. CONCLUSION: Maximum amounts of phosphate that could be added to parenteral nutrition solutions containing Trophamine and calcium chloride were about 7.5-10 mmol/L less for a given concentration of calcium based upon laser methodology compared to visual techniques to determine compatibility. There were minor differences in compatibility when adding calcium chloride and potassium phosphate to Premasol versus Trophamine.

Disease-on-a-chip: mimicry of tumor growth in mammary ducts.

We present a disease-on-a-chip model in which cancer grows within phenotypically normal breast luminal epithelium on semicircular acrylic support mimicking portions of mammary ducts. The cells from tumor nodules developing within these hemichannels are morphologically distinct from their counterparts cultured on flat surfaces. Moreover, tumor nodules cocultured with the luminal epithelium in hemichannels display a different anticancer drug sensitivity compared to nodules cocultured with the luminal epithelium on a flat surface and to monocultures of tumor nodules. The mimicry of tumor development within the epithelial environment of mammary ducts provides a framework for the design and test of anticancer therapies.

Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice.

The GPR30, a former orphan GPCR, is a putative membrane estrogen receptor that can activate rapid signaling pathways such as extracellular regulated kinase (ERK) in a variety of cells and may contribute to estrogen's effects in the central nervous system. The distribution of GPR30 in the limbic system predicts a role for this receptor in the regulation of learning and memory and anxiety by estrogens. Though acute G-1 treatment is reported to be anxiogenic in ovariectomised female mice and in gonadally intact male mice, the effect of GPR30 activation is unknown in gonadectomised male mice. In this study, we show that an acute administration of G-1 to gonadectomised male mice, but not female mice, was anxiolytic on an elevated plus maze task, without affecting locomotor activity. In addition, though G-1 treatment did not regulate ERK, it was associated with increased estrogen receptor (ER)α phosphorylation in the ventral, but not dorsal, hippocampus of males. In the female, G-1 increased the ERK activation solely in the dorsal hippocampus, independent of state anxiety. This is the first study to report an anxiolytic effect of GPR30 activation in male mice, in a rapid time frame that is commensurate with non-genomic signaling by estrogen.

Ticagrelor: a novel reversible oral antiplatelet agent.

The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet medications that are used in addition to aspirin include the thienopyridines, clopidogrel and prasugrel, but there are several limitations to the use of these medications. Clopidogrel and prasugrel irreversibly bind to the P2Y12 receptor, creating a prolonged antiplatelet effect which can be undesirable when surgery is needed. Clopidogrel requires hepatic activation and produces variable platelet inhibition based on genetic polymorphisms. Prasugrel has more consistent platelet inhibition than clopidogrel but carries with it an increased risk of serious bleeds. Ticagrelor is a drug in a new chemical class that reversibly binds the P2Y12 receptor and noncompetitively blocks adenosine diphosphate-induced platelet activation. It was specifically designed to address the limitations of the available antiplatelet agents while maintaining comparable or better antiplatelet effects. It does not require metabolic activation and demonstrates greater platelet inhibition, a faster offset of action and comparable bleeding risk compared to clopidogrel. The pivotal PLATO (The Study of Platelet Inhibition and Patient Outcomes) trial in patients with an acute coronary syndrome demonstrated improved cardiovascular outcomes, including a reduction in myocardial infarctions and vascular events using ticagrelor as compared to clopidogrel with comparable rates of major bleeds. A puzzling finding from that trial was the lack of benefit with ticagrelor in patients enrolled from the United States, which has led to ticagrelor not being approved at this time in this country. The main adverse events with ticagrelor are bleeding and dyspnea, the latter of which is of unclear etiology and of unknown long-term clinical concern. In summary, ticagrelor is an exciting new oral antiplatelet drug that seems to be more efficacious than clopidogrel, with comparable safety. Whether issues of geographic disparities in response and the unusual side effect of dyspnea ultimately prove problematic has yet to be determined. Nonetheless, ticagrelor is a drug that has the potential to change the standard of care of patients with acute coronary syndromes.

Long-term, homologous prolactin, administered through ectopic pituitary grafts, induces hypothalamic dopamine neuron differentiation in adult Snell dwarf mice.

Pituitary prolactin (PRL) secretion is inhibited by dopamine (DA) released into the portal circulation from hypothalamic tuberoinfundibular DA (TIDA) neurons. Ames (df/df) and Snell (dw/dw) dwarf mice lack PRL, GH, and TSH, abrogating feedback and resulting in a reduced hypophysiotropic TIDA population. In Ames df/df, ovine PRL administration for 30 d during early postnatal development increases the TIDA neuron number to normal, but 30 d PRL treatment of adult df/df does not. The present study investigated the effects of homologous PRL, administered via renal capsule pituitary graft surgery for 4 or 6 months, on hypothalamic DA neurons in adult Snell dw/dw mice using catecholamine histofluorescence, tyrosine hydroxylase immunocytochemistry, and bromodeoxyuridine immunocytochemistry. PRL treatment did not affect TIDA neuron number in normal mice, but 4- and 6-month PRL-treated dw/dw had significantly increased (P < or = 0.01) TIDA (area A12) neurons compared with untreated dw/dw. Snell dwarfs treated with PRL for 6 months had more (P < or = 0.01) TIDA neurons than 4-month PRL-treated dw/dw, but lower (P < or = 0.01) numbers than normal mice. Periventricular nucleus (area A14) neuron number was lower in dwarfs than in normal mice, regardless of treatment. Zona incerta (area A13) neuron number was unchanged among phenotypes and treatments. Prolactin was unable to induce differentiation of a normal-sized A14 neuron population in dw/dw. Bromodeoxyuridine incorporation was lower (P < or = 0.01) in 6-month PRL-treated normal mice than in 6-month PRL-treated dwarfs in the subventricular zone of the lateral ventricle and in the dentate gyrus, and lower (P < or = 0.05) in 4-month untreated dwarfs than in 4-month untreated normal mice in the median eminence and the periventricular area surrounding the third ventricle. Thus, a PRL-sensitive TIDA neuron population exists in adult Snell dwarf mice when replacement uses homologous hormone and/or a longer duration. This finding indicates that there is potential for neuronal differentiation beyond early developmental periods and suggests plasticity within the mature hypothalamus.