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Article ; Online: Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats.

Izes, Aaron M / Yu, Jane / Norris, Jacqueline M / Govendir, Merran

2021 Volume 40, Issue 1, Page(s) 322–330

Abstract: Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological ... ...

Abstract	Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient's immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Betacoronavirus ; COVID-19 ; Cats ; Coronavirus Infections/drug therapy ; Coronavirus Infections/veterinary ; Feline Infectious Peritonitis/drug therapy ; Immunologic Factors/therapeutic use ; Pandemics/veterinary ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/veterinary ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Immunologic Factors
Keywords	covid19
Language	English
Publishing date	2021-04-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	754161-2
ISSN	1875-5941 ; 0165-2176
ISSN (online)	1875-5941
ISSN	0165-2176
DOI	10.1080/01652176.2020.1845917
Database	MEDical Literature Analysis and Retrieval System OnLINE

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Intrinsic clearance rate of O-desmethyltramadol (M1) by glucuronide conjugation and phase I metabolism by feline, canine and common brush-tailed possum microsomes.

Izes, Aaron M / Kimble, Benjamin / Govendir, Merran

Xenobiotica; the fate of foreign compounds in biological systems

2019 Volume 50, Issue 7, Page(s) 776–782

Abstract: Quantitative aspects of in vitro phase II glucuronidative metabolism of O-desmethyltramadol (O-DSMT or M1), the active metabolite of the analgesic drug tramadol, by feline, canine and common brush-tailed possum hepatic microsomes are described.Whilst ... ...

Abstract	Quantitative aspects of in vitro phase II glucuronidative metabolism of O-desmethyltramadol (O-DSMT or M1), the active metabolite of the analgesic drug tramadol, by feline, canine and common brush-tailed possum hepatic microsomes are described.Whilst previous studies have focused on the phase I conversion of tramadol to M1, this is the first report in which the phase II glucuronidative metabolic pathway of M1 has been isolated by an in vitro comparative species study.Using the substrate depletion method, microsomal phase II glucuronidative in vitro intrinsic clearance (Clint) of M1 was determined.The in vitro Clint (mean ± SD) by pooled common brush-tailed possum microsomes was 9.9 ± 1.7 μL/min/mg microsomal protein whereas the in vitro Clint by pooled canine microsomes was 1.9 ± 0.07 μL/min/mg microsomal protein. The rate of M1 depletion by feline microsomes, as measured solely by high pressure liquid chromatography, was too slow to determine. Liquid chromatography-mass spectrometry identified O-DSMT glucuronide in samples generated from all three species' microsomes, although the amount detected under the feline condition was minimal.This study indicates that M1 likely undergoes in vitro phase II glucuronidation by canine and common brush-tailed possum microsomes and, to a minor extent, by feline microsomes. The rate of depletion of M1 by phase I metabolism was also undertaken.When incubated with phase I co-factors and common brush-tailed possum microsomes or canine microsomes, M1 had an in vitro Clint of 47.6 and 22.8 μL/min/mg microsomal protein, respectively. However, due to a lack of CYP2B-like activity in the feline liver, unsurprisingly, M1 did not deplete when incubated with feline microsomes. Consequently, major M1 elimination pathways, using feline microsomes, were not determined."
MeSH term(s)	Animals ; Cats ; Dogs ; Glucuronides/metabolism ; Humans ; Metabolic Clearance Rate ; Microsomes/metabolism ; Tramadol/analogs & derivatives ; Tramadol/metabolism ; Trichosurus/metabolism
Chemical Substances	Glucuronides ; O-demethyltramadol (2WA8F50C3F) ; Tramadol (39J1LGJ30J)
Language	English
Publishing date	2019-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	120287-x
ISSN	1366-5928 ; 0049-8254
ISSN (online)	1366-5928
ISSN	0049-8254
DOI	10.1080/00498254.2019.1697014
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats.

Izes, Aaron M / Kimble, Benjamin / Norris, Jacqueline M / Govendir, Merran

PloS one

2020 Volume 15, Issue 8, Page(s) e0236754

Abstract: The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma ... ...

Abstract	The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay's lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%).
MeSH term(s)	Animals ; Blood Proteins/genetics ; Caliciviridae Infections/drug therapy ; Caliciviridae Infections/veterinary ; Caliciviridae Infections/virology ; Calicivirus, Feline/drug effects ; Calicivirus, Feline/pathogenicity ; Cats ; Coronavirus, Feline/drug effects ; Coronavirus, Feline/pathogenicity ; Feline Infectious Peritonitis/blood ; Feline Infectious Peritonitis/drug therapy ; Feline Infectious Peritonitis/virology ; Mefloquine/pharmacology ; Protein Binding/drug effects
Chemical Substances	Blood Proteins ; Mefloquine (TML814419R)
Keywords	covid19
Language	English
Publishing date	2020-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0236754
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats

Izes, Aaron M / Yu, Jane / Norris, Jacqueline M / Govendir, Merran

Veterinary quarterly. 2020 Jan. 1, v. 40, no. 1

2020

Abstract	Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient’s immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.
Keywords	Feline coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; adenosine ; cats ; feline infectious peritonitis ; humans ; immune response ; immune system ; immunosuppression ; pandemic ; patients ; proteinase inhibitors ; therapeutics ; virulence ; viruses
Language	English
Dates of publication	2020-0101
Size	p. 322-330.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	754161-2
ISSN	1875-5941 ; 0165-2176
ISSN (online)	1875-5941
ISSN	0165-2176
DOI	10.1080/01652176.2020.1845917
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 4127: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats.

Aaron M Izes / Benjamin Kimble / Jacqueline M Norris / Merran Govendir

PLoS ONE, Vol 15, Iss 8, p e

2020 Volume 0236754

Abstract	The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay's lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%).
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats

Aaron M. Izes / Jane Yu / Jacqueline M. Norris / Merran Govendir

Veterinary Quarterly, Vol 40, Iss 1, Pp 322-

2020 Volume 330

Abstract	Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient’s immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.
Keywords	cat ; feline ; feline infectious peritonitis ; fip ; feline infectious peritonitis virus ; therapeutics ; treatment ; sars-cov-2 ; Veterinary medicine ; SF600-1100
Subject code	630
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats

Izes, Aaron M. / Yu, Jane / Norris, Jacqueline M. / Govendir, Merran

Veterinary Quarterly

2020 , Page(s) 1–13

Keywords	General Veterinary ; covid19
Language	English
Publisher	Informa UK Limited
Publishing country	uk
Document type	Article ; Online
ZDB-ID	754161-2
ISSN	1875-5941 ; 0165-2176
ISSN (online)	1875-5941
ISSN	0165-2176
DOI	10.1080/01652176.2020.1845917
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula).

Izes, Aaron Michael / Kimble, Benjamin / Norris, Jacqueline Marie / Govendir, Merran

PloS one

2020 Volume 15, Issue 4, Page(s) e0230975

Abstract: Feline infectious peritonitis (FIP) is a systemic, fatal, viral-induced, immune-mediated disease of cats caused by feline infectious peritonitis virus (FIPV). Mefloquine, a human anti-malarial agent, has been shown to inhibit FIPV in vitro. As a first ... ...

Abstract	Feline infectious peritonitis (FIP) is a systemic, fatal, viral-induced, immune-mediated disease of cats caused by feline infectious peritonitis virus (FIPV). Mefloquine, a human anti-malarial agent, has been shown to inhibit FIPV in vitro. As a first step to evaluate its efficacy and safety profile as a potential FIP treatment for cats, mefloquine underwent incubation in feline, canine and common brush-tailed possum microsomes and phase I metabolism cofactors to determine its rate of phase I depletion. Tramadol was used as a phase I positive control as it undergoes this reaction in both dogs and cats. Using the substrate depletion method, the in vitro intrinsic clearance (mean ± S.D.) of mefloquine by pooled feline and common brush-tailed possum microsomes was 4.5 ± 0.35 and 18.25 ± 3.18 μL/min/mg protein, respectively. However, phase I intrinsic clearance was too slow to determine with canine microsomes. Liquid chromatography-mass spectrometry (LC-MS) identified carboxymefloquine in samples generated by feline microsomes as well as negative controls, suggesting some mefloquine instability. Mefloquine also underwent incubation with feline, canine and common brush-tailed possum microsomes and phase II glucuronidative metabolism cofactors. O-desmethyltramadol (ODMT or M1) was used as a positive control as it undergoes a phase II glucuronidation reaction in these species. The rates of phase II mefloquine depletion by microsomes by all three species were too slow to estimate. Therefore mefloquine likely undergoes phase I hepatic metabolism catalysed by feline and common brush-tailed possum microsomes but not phase II glucuronidative metabolism in all three species and mefloquine is not likely to have delayed elimination in cats with clinically normal, hepatic function.
MeSH term(s)	Animals ; Antimalarials/metabolism ; Antimalarials/pharmacokinetics ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacokinetics ; Caliciviridae Infections/drug therapy ; Caliciviridae Infections/metabolism ; Caliciviridae Infections/veterinary ; Calicivirus, Feline ; Cats ; Coronavirus, Feline ; Dogs ; Drug Repositioning/veterinary ; Feline Infectious Peritonitis/drug therapy ; Feline Infectious Peritonitis/metabolism ; Feline Infectious Peritonitis/virology ; In Vitro Techniques ; Mefloquine/metabolism ; Mefloquine/pharmacokinetics ; Metabolic Clearance Rate ; Microsomes, Liver/metabolism ; Species Specificity ; Trichosurus/metabolism
Chemical Substances	Antimalarials ; Antiviral Agents ; Mefloquine (TML814419R)
Keywords	covid19
Language	English
Publishing date	2020-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0230975
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats

Izes, Aaron M / Yu, Jane / Norris, Jacqueline M / Govendir, Merran

Vet Q

Abstract	Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient's immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #900144
Database	COVID19

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Article: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats

Izes, Aaron M / Kimble, Benjamin / Norris, Jacqueline M / Govendir, Merran

PLoS One

Abstract	The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay's lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%).
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #712730
Database	COVID19

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