Does wearing a noseclip during inhalation improve lung deposition?

Using nebulization, only a small proportion of the dose reaches the lungs, while the remainder is swallowed, exhaled into the atmosphere, or remains in the nebulizer. It was the purpose of this study to investigate whether wearing a noseclip during inhalation can improve lung deposition. Relative lung deposition was compared by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. The SCG absorption half-life allows one to differentiate indirectly between a more or less peripheral deposition. Ten CF patients (9-18 years old) inhaled, under routine conditions, a solution containing 20 mg of SCG in a randomized crossover design through a mouthpiece, without and with a noseclip being worn. Following inhalation without and with a noseclip, no statistically significant difference was seen in the amount of SCG excreted in urine (0.9 +/- 0.4 mg vs. 1.0 +/- 0.5 mg; p = 0.402) and absorption half-life (93 +/- 25 min vs. 113 +/- 36 min; p = 0.083). In conclusion, wearing a noseclip during inhalation under conditions relevant to practice does not increase the amount deposited into the lungs of CF patients and, also, there has been no indication of a more peripheral lung deposition.     

Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye.

In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore profiled urinary [(14)C]-metabolites and NAT2 genotype in eight human subjects following treatment with a dark-shade oxidative hair dye containing [(14)C]-para-phenylenediamine (PPD). Genotyping identified three subjects as slow, and five subjects as intermediate NAT2 acetylators. Within 24 h after treatment, the study subjects excreted a mean total of 0.43+/-0.24% of the applied [(14)C] in the urine, where five different metabolites were found. The major urinary metabolites were concluded to be N-mono-acetylated and N,N'-diacetylated PPD. They were present in all urine samples and amounted to 80-95% of the total urinary [(14)C]. Another metabolite, possibly a glucuronic acid conjugate, was found in 6/8 urine samples at 5-13% of the total urinary [(14)C]. All metabolites appeared to be related to PPD, no evidence of the presence of high-molecular weight dye-intermediates or corresponding metabolites was found. The metabolite profile in the study subjects showed no significant differences between the NAT2 intermediate and NAT2 slow acetylator subgroups. Urine of NAT2 slow acetylators contained N-mono-acetylated-PPD at 42.2+/-10.2% and N,N'-di-acetylated-PPD at 54.1+/-7.6% of total urinary radioactivity, while the corresponding values of intermediate acetylators were 46.0+/-8.9% and 45.7+/-9.9%, respectively. Overall, our results suggest that the human acetylation rate of PPD after topical application is independent of the NAT2 genotype status, most likely due to metabolism by epidermal NAT1 prior to systemic absorption.     

Promises and pitfalls of untargeted metabolomics

Metabolomics is one of the newer omics fields, and has enabled researchers to complement genomic and protein level analysis of disease with both semi-quantitative and quantitative metabolite levels, which are the chemical mediators that constitute a given phenotype. Over more than a decade, methodologies have advanced for both targeted (quantification of specific analytes) as well as untargeted metabolomics (biomarker discovery and global metabolite profiling). Untargeted metabolomics is especially useful when there is no a priori metabolic hypothesis. Liquid chromatography coupled to mass spectrometry (LC-MS) has been the preferred choice for untargeted metabolomics, given the versatility in metabolite coverage and sensitivity of these instruments. Resolving and profiling many hundreds to thousands of metabolites with varying chemical properties in a biological sample presents unique challenges, or pitfalls. In this review, we address the various obstacles and corrective measures available in four major aspects associated with an untargeted metabolomics experiment: (1) experimental design, (2) pre-analytical (sample collection and preparation), (3) analytical (chromatography and detection), and (4) post-analytical (data processing).     

Financial incentives,timing of births,and infant health: a closer look into the delivery room

As a result of strong financial incentives created by the German parental leave reform on January 1, 2007, some 1000 births have been shifted from the last days of 2006 to the first days of 2007, especially by working mothers. This fact is already described in the literature, yet there is no evidence as to the mechanisms and only scarce evidence regarding the effects on newborn health. I use new data to study the timing of C-sections and the induction of births around the day the reform took effect. I estimate that postponed C-sections and inductions account for nearly 80 % of the pre-reform shortfall and nearly 90 % of the post-reform excess number of births. Despite concerns voiced by doctors before the reform, hardly any evidence can be found for detrimental health effects of those shifts, as measured by changes in gestational age, birth weight, APGAR scores, neonatal mortality, or hospitalization.     

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences,and Regulation by Paclitaxel

Voltage-gated sodium channels(Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion(hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7(~50% of total Nav expression) and lower expression of Nav1.8(~12%), whereas the mouse DRG has higher expression of Nav1.8(~45%) and lower expression of Nav1.7(~18%). To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel(0.1-1 μmol/L) for 24 h. Paclitaxel increased the Nav 1.7 but not Nav1.8 expression and also increased the transient Na~+ currents and action potential firing frequency in small-diameter(50 μm) hDRG neurons. Thus, the hDRG provides a translational model in which to study"human pain in a dish" and test new pain therapeutics.