Device for the Capture and Extraction of Waste Anesthetic Gas

Background: Leaks occur often throughout the process of delivering inhaled anesthesia prior to and during surgery. Leaks typically occur around the patient’s mouth, nose, and eyes. Potent inhaled anesthetics (PIAs) include halothane, sevoflurane, desflurane, and isoflurane. All PIAs, to one degree or another, pose hazards to human health. PIAs are associated with reproductive toxicity, spontaneous miscarriages in pregnant persons as well as an increased risk of congenital abnormalities in offspring. In other words, PIAs are thought to be both abortifacients as well as teratogens. PIAs are also associated with hepatotoxicity, neurotoxicity, cognitive impairment, as well as increased incidence of malignancy. Methods: Preliminary interviews with stakeholders were conducted to assess the desirability, viability, and utility of a product to trap and remove waste anesthetic gas (WAG) from the perifacial region before it diffuses into the ambient air. We used wearable detector badges (similar to a dosimeter) from Assay Technology Inc. for qualitative measurements of WAG levels in several operating rooms. We used low-fidelity mockups for early prototyping, FDM and SLA 3D printing techniques, and urethane casts for high-fidelity working prototypes. We also performed real-time simulations using a visible aerosol agent in order to record and study the efficacy of our device. Results: We found dramatically elevated levels of sevoflurane in the operating room, with our highest readings at ~10x NIOSH permissible exposure limits. With our visual simulation we saw a markedly reduced flow of WAG into the surrounding air. Conclusions: Our device adequately addresses a significant and unaddressed issue in healthcare and shows viability from an economic standpoint as well. We are currently designing a study to further evaluate levels of WAG and exploring potential studies with live anesthetic agents

Scavenger of Waste Anesthetic

Waste anesthetic gases (WAGs) are associated with spontaneous miscarriages in pregnant persons, an increased risk of congenital abnormalities, hepatotoxicity, neurotoxicity, and cognitive impairment. Through monitoring anesthesiologists we found levels of WAGs to be 5-10x the current standard inside the OR. Currently, no solutions exist for the mitigation of WAG release. Remora is a solution to removing WAGs that fits on top of existing anesthesia masks. A flexible skirt is joined to a rigid ring, which deforms under hand pressure to facilitate effective hand-to-mask placement. The suction system is plugged into an unused suction port to create an area under the anesthesia mask that is depressurized, creating circumferential suction around the mask. The negative pressure gradient between the Remora-mask unit and room air pulls WAGs into the gap between the anesthesia mask and Remora, and then into the anesthesia machine\u27s suction system. From there, WAGs are exhausted into the air handling system which receives other waste gases. Using visible gas we were able to show how much WAGs may be escaping during induction and the amount Remora was able to scavenge. While we were unable to quantify our results, we were able to qualitatively show that the amount of gas was significantly less once Remora was turned on. Our hope is to perform further studies to prove that with the use of Remora the concentration of WAGs will decrease in the OR and decrease the negative side effects associated with WAGs

Caspase Inhibitors of the P35 Family Are More Active When Purified from Yeast than Bacteria

Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a “reactive site loop” within the P35 protein, which ultimately leaves cleaved P35 covalently bound to the caspase's active site. We observed that AcP35 purifed from Saccharomyces cerevisae inhibited caspase activity more efficiently than AcP35 purified from Escherichia coli. This differential potency was more dramatic for another P35 family member, MaviP35, which inhibited human caspase 3 almost 300-fold more potently when purified from yeast than bacteria. Biophysical assays revealed that MaviP35 proteins produced in bacteria and yeast had similar primary and secondary structures. However, bacterially produced MaviP35 possessed greater thermal stability and propensity to form higher order oligomers than its counterpart purified from yeast. Caspase 3 could process yeast-purified MaviP35, but failed to detectably cleave bacterially purified MaviP35. These data suggest that bacterially produced P35 proteins adopt subtly different conformations from their yeast-expressed counterparts, which hinder caspase access to the reactive site loop to reduce the potency of caspase inhibition, and promote aggregation. These data highlight the differential caspase inhibition by recombinant P35 proteins purified from different sources, and caution that analyses of bacterially produced P35 family members (and perhaps other types of proteins) may underestimate their activity

A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier

BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases

Unusual Structures, Phase Behavior, and Fluorescent Properties of 3-phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine and Its’ ZnCl2 Complex

The synthesis and single crystal structures of 3-phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine (L1) and its complex with ZnCl2 are reported. L1 exhibits supercooling, with a difference in melting and solidification points of over 100 oC. The complex [L1ZnCl2] has a room-to-low temperature single crystal-to-crystal phase transition in the solid state, while a birefringent fluid phase mixed with crystalline domains is observed at high temperatures. Significant fluorescence enhancement is observed upon formation of the ZnCl2 complex

A conserved role for non-neural ectoderm cells in early neural development

During the early steps of head development, ectodermal patterning leads to the emergence of distinct non-neural and neural progenitor cells. The induction of the preplacodal ectoderm and the neural crest depends onwell-studied signalling interactions between the non-neural ectoderm fated to become epidermis and the prospective neural plate. By contrast, the involvement of the non-neural ectoderm in the morphogenetic events leading to the development and patterning of the central nervous systemhas been studied less extensively. Here,we show that the removal of the rostral non-neural ectoderm abutting the prospective neural plate at late gastrulation stage leads, in mouse and chick embryos, to morphological defects in forebrain and craniofacial tissues. In particular, this ablation compromises the development of the telencephalon without affecting that of the diencephalon. Further investigations of ablated mouse embryos established that signalling centres crucial for forebrain regionalization, namely the axial mesendoderm and the anterior neural ridge, form normally. Moreover, changes in cell death or cell proliferation could not explain the specific loss of telencephalic tissue. Finally, we provide evidence that the removal of rostral tissues triggers misregulation of the BMP, WNT and FGF signalling pathways that may affect telencephalon development. This study opens new perspectives on the role of the neural/non-neural interface and reveals its functional relevance across higher vertebrates.status: publishe