Clinical Olfactory Working Group Consensus statement on the treatment of post infectious olfactory dysfunction

Background: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). Objective: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post–coronavirus 2019 cases) for both primary care practitioners and hospital specialists. Methods: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. Results: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. Conclusions: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options

Conditioned place avoidance of zebrafish (Danio rerio) to three chemicals used for euthanasia

Zebrafish are increasingly used as a vertebrate model organism for developmental and biomedical research. These fish are commonly euthanized at the end of an experiment with an overdose of tricaine methanesulfonate (TMS), but to date little research has assessed if exposure to this or other agents meets the criteria of a “good death”. Clove oil and metomidate hydrochloride are alternatives to TMS and have been approved for use in several countries. The aim of my thesis was to use a conditioned place avoidance paradigm to compare aversion to TMS, metomidate, and clove oil. Zebrafish showed a natural preference for the light environment (in a 900-s trial, they spend 95% of their time in the light compartment); by exposing them to anaesthetics in the light side of a light-dark box we were able to show a difference in preference after exposure. Conditioned place avoidance was less pronounced for fish exposed to metomidate and clove oil than for TMS; fish exposed to the former reduced the time spent in the preferred light side by 131 ± 68 s and 165 ± 97 s, respectively, versus a reduction of 591 ± 88 s for those exposed to the TMS. Complete rejection, where no attempted entries were made into the light side, were recorded after exposure to anaesthetics. Nine of 17 fish exposed to TMS did not re-enter the previously preferred side, versus 2 of 18 fish and 3 of 16 fish for metomidate and clove oil, respectively. These results suggest that the use of metomidate and clove oil are humane alternatives to TMS and should be considered when euthanizing zebrafish.Land and Food Systems, Faculty ofGraduat

Data from: Rat aversion to isoflurane versus carbon dioxide

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO2) is a humane alternative to euthanasia with CO2 alone, but little research has compared aversion to these agents. Albino rats were tested in a light/dark box where they had the choice between remaining in a dark compartment filling with isoflurane or CO2, or escaping to a lit compartment. Experiment 1 validated the procedure by confirming that rats responded to agent and light intensity. In Experiment 2, 9/16 and 0/16 rats remained in the dark compartment until recumbent when initially exposed to isoflurane and CO2, respectively. In Experiment 3, more rats remained in the dark compartment until recumbent during initial (10/16) versus re-exposure (1/16) to isoflurane. These results indicate that initial exposure to CO2 is more aversive than isoflurane, and that re-exposure to isoflurane is more aversive than initial exposure. We conclude that sedation with isoflurane is a refinement over euthanasia with CO2 alone for rats that have not been previously exposed to inhalant anaesthetics

Time spent in dark compartment during gas exposure

This data was collected in the UBC Centre for Disease Modelling from 2010-2011. Three experiments were carried out separately, with each tab in the excel file representing one experiment. There are two abbreviations: "ISO" represents isoflurane and "CO2" represents carbon dioxide

Conditioned Place Avoidance of Zebrafish (<i>Danio rerio</i>) to Three Chemicals Used for Euthanasia and Anaesthesia

<div><p>Zebrafish are becoming one of the most used vertebrates in developmental and biomedical research. Fish are commonly killed at the end of an experiment with an overdose of tricaine methanesulfonate (TMS, also known as MS-222), but to date little research has assessed if exposure to this or other agents qualifies as euthanasia (i.e. a “good death”). Alternative agents include metomidate hydrochloride and clove oil. We use a conditioned place avoidance paradigm to compare aversion to TMS, clove oil, and metomidate hydrochloride. Zebrafish (n = 51) were exposed to the different anaesthetics in the initially preferred side of a light/dark box. After exposure to TMS zebrafish spent less time in their previously preferred side; aversion was less pronounced following exposure to metomidate hydrochloride and clove oil. Nine of 17 fish exposed to TMS chose not to re-enter the previously preferred side, versus 2 of 18 and 3 of 16 refusals for metomidate hydrochloride and clove oil, respectively. We conclude that metomidate hydrochloride and clove oil are less aversive than TMS and that these agents be used as humane alternatives to TMS for killing zebrafish.</p></div

Mean and standard deviation for test doses of the three euthanasia agents.

<p>Mean±S.D. times to loss of equilibrium for three doses of TMS (n = 10), clove oil (n = 10), and metomidate hydrochloride (n = 10). These values were used to determine equipotent concentrations by graphical interpolation.</p

Number of fish choosing not to enter the light compartment after exposure to three euthanasia agents.

<p>Complete rejection was defined as no attempted entries into the previously preferred light compartment. Fish were tested following exposure to TMS (n = 17), clove oil (n = 16), and metomidate hydrochloride (n = 18).</p

Total time spent in the ‘preferred’ compartment pre- and post- exposure to three euthanasia agents.

<p>Total time spent (s) in the light compartment, preferred by all fish before exposure to TMS (a; n = 17), clove oil (b; n = 16), and metomidate hydrochloride (c; n = 18). Times spent are also shown after exposure to these agents. The black bar represents the median. Each square dot shows the value of a single fish. Duplicate values are superimposed.</p

Diagram of testing apparatus.

<p>The testing apparatus, consisting of a light and dark side identical in size. During the initial preference determination period (a) we simply monitored the time spent on the two-sides of the tank (all fish tested preferred the light side). Fish were then exposed to one of three anaesthetics while in the light side of the tank (b). Once fish recovered we re-tested preference (following the identical procedure as used in panel a) with the apparatus once again free of anaesthetics (c).</p