PMC:7204663 / 7591-8845 JSONTXT

{"project":"LitCovid-PubTator","denotations":[{"id":"83","span":{"begin":51,"end":63},"obj":"Chemical"},{"id":"84","span":{"begin":195,"end":213},"obj":"Chemical"},{"id":"85","span":{"begin":239,"end":251},"obj":"Chemical"},{"id":"86","span":{"begin":337,"end":350},"obj":"Chemical"},{"id":"87","span":{"begin":401,"end":413},"obj":"Chemical"},{"id":"88","span":{"begin":500,"end":512},"obj":"Chemical"},{"id":"89","span":{"begin":636,"end":648},"obj":"Chemical"}],"attributes":[{"id":"A83","pred":"tao:has_database_id","subj":"83","obj":"MESH:D017963"},{"id":"A84","pred":"tao:has_database_id","subj":"84","obj":"MESH:D006886"},{"id":"A85","pred":"tao:has_database_id","subj":"85","obj":"MESH:D017963"},{"id":"A86","pred":"tao:has_database_id","subj":"86","obj":"MESH:D010743"},{"id":"A87","pred":"tao:has_database_id","subj":"87","obj":"MESH:D017963"},{"id":"A88","pred":"tao:has_database_id","subj":"88","obj":"MESH:D017963"},{"id":"A89","pred":"tao:has_database_id","subj":"89","obj":"MESH:D017963"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

{"project":"2_test","denotations":[{"id":"32389720-7558665-48149098","span":{"begin":352,"end":354},"obj":"7558665"},{"id":"32389720-12441132-48149099","span":{"begin":358,"end":360},"obj":"12441132"},{"id":"32389720-11499789-48149100","span":{"begin":364,"end":366},"obj":"11499789"},{"id":"32389720-8957238-48149101","span":{"begin":370,"end":372},"obj":"8957238"},{"id":"32389720-25155592-48149102","span":{"begin":438,"end":440},"obj":"25155592"},{"id":"32389720-25155592-48149103","span":{"begin":1089,"end":1091},"obj":"25155592"},{"id":"32389720-431047-48149104","span":{"begin":1095,"end":1097},"obj":"431047"},{"id":"32389720-12243724-48149105","span":{"begin":1101,"end":1103},"obj":"12243724"},{"id":"32389720-1030706-48149106","span":{"begin":1107,"end":1109},"obj":"1030706"},{"id":"T35193","span":{"begin":352,"end":354},"obj":"7558665"},{"id":"T71814","span":{"begin":358,"end":360},"obj":"12441132"},{"id":"T86676","span":{"begin":364,"end":366},"obj":"11499789"},{"id":"T46347","span":{"begin":370,"end":372},"obj":"8957238"},{"id":"T79422","span":{"begin":438,"end":440},"obj":"25155592"},{"id":"T99834","span":{"begin":1089,"end":1091},"obj":"25155592"},{"id":"T30874","span":{"begin":1095,"end":1097},"obj":"431047"},{"id":"T42597","span":{"begin":1101,"end":1103},"obj":"12243724"},{"id":"T58158","span":{"begin":1107,"end":1109},"obj":"1030706"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

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{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T2","span":{"begin":555,"end":560},"obj":"Body_part"},{"id":"T3","span":{"begin":854,"end":859},"obj":"Body_part"}],"attributes":[{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T7","span":{"begin":788,"end":796},"obj":"Disease"}],"attributes":[{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0006591"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T67","span":{"begin":100,"end":109},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T68","span":{"begin":149,"end":151},"obj":"http://purl.obolibrary.org/obo/CLO_0001407"},{"id":"T69","span":{"begin":253,"end":254},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T70","span":{"begin":297,"end":306},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T71","span":{"begin":358,"end":360},"obj":"http://purl.obolibrary.org/obo/CLO_0053733"},{"id":"T72","span":{"begin":375,"end":376},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T73","span":{"begin":414,"end":423},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T74","span":{"begin":555,"end":566},"obj":"http://www.ebi.ac.uk/efo/EFO_0000296"},{"id":"T75","span":{"begin":765,"end":771},"obj":"http://purl.obolibrary.org/obo/UBERON_0001630"},{"id":"T76","span":{"begin":765,"end":771},"obj":"http://purl.obolibrary.org/obo/UBERON_0005090"},{"id":"T77","span":{"begin":765,"end":771},"obj":"http://www.ebi.ac.uk/efo/EFO_0000801"},{"id":"T78","span":{"begin":765,"end":771},"obj":"http://www.ebi.ac.uk/efo/EFO_0001949"},{"id":"T79","span":{"begin":788,"end":796},"obj":"http://purl.obolibrary.org/obo/UBERON_0002072"},{"id":"T80","span":{"begin":854,"end":865},"obj":"http://www.ebi.ac.uk/efo/EFO_0000296"},{"id":"T81","span":{"begin":985,"end":994},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T82","span":{"begin":1078,"end":1087},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T83","span":{"begin":1179,"end":1188},"obj":"http://purl.obolibrary.org/obo/GO_0005764"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T52","span":{"begin":14,"end":17},"obj":"Chemical"},{"id":"T53","span":{"begin":51,"end":63},"obj":"Chemical"},{"id":"T54","span":{"begin":195,"end":213},"obj":"Chemical"},{"id":"T55","span":{"begin":239,"end":251},"obj":"Chemical"},{"id":"T56","span":{"begin":337,"end":350},"obj":"Chemical"},{"id":"T57","span":{"begin":401,"end":413},"obj":"Chemical"},{"id":"T58","span":{"begin":500,"end":512},"obj":"Chemical"},{"id":"T59","span":{"begin":636,"end":648},"obj":"Chemical"}],"attributes":[{"id":"A52","pred":"chebi_id","subj":"T52","obj":"http://purl.obolibrary.org/obo/CHEBI_24870"},{"id":"A53","pred":"chebi_id","subj":"T53","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A54","pred":"chebi_id","subj":"T54","obj":"http://purl.obolibrary.org/obo/CHEBI_5801"},{"id":"A55","pred":"chebi_id","subj":"T55","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A56","pred":"chebi_id","subj":"T56","obj":"http://purl.obolibrary.org/obo/CHEBI_16247"},{"id":"A57","pred":"chebi_id","subj":"T57","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A58","pred":"chebi_id","subj":"T58","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A59","pred":"chebi_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}

{"project":"LitCovid-sentences","denotations":[{"id":"T62","span":{"begin":0,"end":214},"obj":"Sentence"},{"id":"T63","span":{"begin":215,"end":374},"obj":"Sentence"},{"id":"T64","span":{"begin":375,"end":442},"obj":"Sentence"},{"id":"T65","span":{"begin":443,"end":596},"obj":"Sentence"},{"id":"T66","span":{"begin":597,"end":809},"obj":"Sentence"},{"id":"T67","span":{"begin":810,"end":968},"obj":"Sentence"},{"id":"T68","span":{"begin":969,"end":1254},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"When the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations."}