Environmental life-cycle inventory of detergent-grade surfactant sourcing and production

Life-cycle inventories were compiled to characterize natural resource requirements and environmental emissions associated with the sourcing and production of selected, detergent-grade surfactants and surfactant feedstocks. Petrochemical surfactant types examined were linear alkylbenzene sulfonate, alcohol sulfate (AS), alcohol ethoxylate (AE) and alcohol ethoxylate sulfate (AES). Oleochemical surfactants derived from palm oil, palm kernel oil and inedible tallow were AS, AE, AES and (for palm oil and tallow) methyl ester sulfonate. It was determined that natural resource requirements were primarily related to the source of feedstock and secondarily to surfactant type. Likewise, the composition and mass of atmospheric, aqueous and solid emissions were principally determined by feedstock source. Energy requirements varied as a function of both feedstock and surfactant type. The inventories do not support fundamental shifts in surfactant usage or feedstock sourcing on the basis of environmental concerns, as no single surfactant or feedstock was identified as superior across all resource and emissions criteria examined. The data provide baselines for evaluating opportunities for resource optimization, pollution prevention and waste minimization within each production technology surveyed.     

The in vitro and in vivo investigation of inhaled migraine therapies using a novel aerosol delivery system consisting of an air pressurized capsule device (APCD) in combination with a pMDI spacer for endotracheal dosing into beagle dogs

Abstract

Context: Aerosol delivery to animals in preclinical settings has historically been very challenging, requiring the use of techniques, such as intratracheal instillation and dry powder insufflation, that are somewhat invasive, inefficient and not representative of clinical inhalation.

Objective: The objective of this work is to develop a system to deliver dry powder to dogs in an efficient and effective manner for the study of new anti-migraine compounds in development.

Materials and methods: The new device uses a metered aliquot of a dry gas to force dry powder drug from a pre-filled HPMC capsule into an AeroChamber® spacer for subsequent inhalation by the animal.

Results: The delivery of two invesigational migraine drugs via the new device was assessed in vitro using abbreviated Andersen cascade impaction and showed the device is capable of generating a reproducible delivered dose of up to ～68% with more than 50% of the dose in the respirable range. In vivo studies have also been performed showing that this device effectively delivered the migraine drugs to spontaneously breathing dogs using a proprietary validated dog inhalation model.

Discussion: Results confirmed that the air pressurized capsule device (APCD) was effective in delivering the APIs to lungs of the animals. The in vivo data verified the advantages of inhaled delivery over oral delivery for this class of drugs and were used to establish the cardiopulmonary and respiratory side effect liability profile for these compounds.

Conclusions: This work has demonstrated the utility of this device for quick and accurate screening of prospective drug candidates, representing a significant improvement in ease of use and reprodicibility over current delivery methods.     

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.     

Phase 1B ventricular arrhythmia in the dog: localized reentry within the mid-myocardium

Our aim was to investigate the relationships between defensiveness and repression, on the one hand, and self-reported stressor exposure and resting blood pressure, on the other hand. In addition, different operationalizations of defensiveness and repression were compared. Participants were 310 male and 90 female employees representing a wide range of occupations. Before a medical examination, all subjects completed questionnaires measuring defensiveness, anxiety, repression, daily hassles, and life events. After controlling for potentially confounding variables, multiple regression analyses revealed an inverse association between defensiveness and self-reported number of daily hassles and a positive link between defensiveness and resting systolic blood pressure. In general, the interaction between defensiveness and anxiety (representing repression) did not add to the predictive power of defensiveness and anxiety alone. The results support the notion that defensive individuals tend to underreport problems, while exhibiting elevated resting blood pressures.