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Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency
Summary objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated wi...
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| Published in: | Clinical endocrinology (Oxford) 2002-04, Vol.56 (4), p.449-455 |
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| creator | Smith, J. C. Lang, D. McEneny, J. Evans, L. M. Scanlon, M. F. Young, I. Davies, J. |
| description | Summary
objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated with adult GHD.
design and patients In a randomized, double‐blind, placebo‐controlled study we investigated the effects of GH replacement on low‐density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age‐ and sex‐matched healthy controls were also studied.
measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper‐catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin‐based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.
results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P |
| doi_str_mv | 10.1046/j.1365-2265.2002.01493.x |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71645958</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71645958</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4333-440ff94bb99d904fe5e3966c15bafb62aca3b9e33ac33a07444a5c20f61629783</originalsourceid><addsrcrecordid>eNqNkE-P1CAYxonRuOPqVzBc9NYKhdLh4MGM46zJZjRG45FQ-rLD2KEV2uz06ieXOs3u1QOB8Pye98-DEKYkp4SLd8ecMlFmRSHKvCCkyAnlkuXnJ2j1IDxFK8IIyYgQ_Aq9iPFICCnXpHqOriiVQlSsWqE_W2vBDBF3Fu9ucOdx63rX4B5Cd3aNHlz60r7BHsYhdP3BtTiOiwpJSXp2Bx5CQv0dNrrXxg0Tdh4fpr7r3TC6QYcJ62ZsU597NxzmTg1YZxx4M71Ez6xuI7xa7mv049P2--Ymu_2y-7z5cJsZzhjLOCfWSl7XUjaScAslsLSFoWWtbS0KbTSrJTCmTTqk4pzr0hTECioKWa3ZNXp7qduH7vcIcVAnFw20rfbQjVFVVPBSljO4voAmdDEGsKoP7pR2UJSoOX91VHPMao5Zzfmrf_mrc7K-XnqM9QmaR-MSeALeLICORrc2aG9cfORYVVVyTRP3_sLduxam_x5Abbb7-ZX82cXv4gDnB78Ov9Q8R6l-7neK7XcfJf32VTH2F9kWsi8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71645958</pqid></control><display><type>article</type><title>Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency</title><source>Wiley</source><creator>Smith, J. C. ; Lang, D. ; McEneny, J. ; Evans, L. M. ; Scanlon, M. F. ; Young, I. ; Davies, J.</creator><creatorcontrib>Smith, J. C. ; Lang, D. ; McEneny, J. ; Evans, L. M. ; Scanlon, M. F. ; Young, I. ; Davies, J.</creatorcontrib><description><![CDATA[Summary
objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated with adult GHD.
design and patients In a randomized, double‐blind, placebo‐controlled study we investigated the effects of GH replacement on low‐density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age‐ and sex‐matched healthy controls were also studied.
measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper‐catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin‐based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.
results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P < 0·01) and higher triglyceride concentrations (2·3 ± 1·5 vs. 1·1 ± 0·7 mmol/l, P < 0·001) but lower HDL cholesterol (1·1 ± 0·3 mmol/l vs. 1·4 ± 0·4 mmol/l, P < 0·01), lower levels of HPOs (0·72 ± 0·35 vs. 0·92 ± 0·20 µm, P < 0·01) and lower basal (2·5 ± 1·5 vs. 4·5 ± 2·3 mV/5 × 105 neutrophils, P < 0·01) and peak post‐activation levels (23·2 ± 11·1 vs. 34·4 ± 15·6 mV/5 × 105 neutrophils, P < 0·01) of neutrophil O2− generation. GH replacement resulted in an increase in HPOs from 0·70 ± 0·39 to 0·86 ± 0·19 µm (P < 0·05), although there was no change in the lag time of LDL oxidation. Neutrophil O2− generating capacity was enhanced with a rise in basal O2− generation from 2·8 ± 1·4 to 5·4 ± 4·6 mV/5 × 105 neutrophils (P < 0·05) and in peak post‐activation O2− generation from 21·9 ± 9·5 to 35·8 ± 21·7 mV/5 × 105 neutrophils (P < 0·05). LDL cholesterol was reduced from 4·1 ± 0·8 mmol/l to 3·5 ± 0·8 mmol/l (P < 0·01). No significant changes in measured parameters occurred in the placebo group.
conclusions Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O2− generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro‐atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte–lipoprotein interactions.]]></description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1046/j.1365-2265.2002.01493.x</identifier><identifier>PMID: 11966737</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Biological and medical sciences ; Double-Blind Method ; Female ; Hormones. Endocrine system ; Human Growth Hormone - deficiency ; Human Growth Hormone - pharmacology ; Human Growth Hormone - therapeutic use ; Humans ; Hypopituitarism - blood ; Hypopituitarism - physiopathology ; Lipid Peroxidation - drug effects ; Lipoproteins, LDL - blood ; Male ; Medical sciences ; Middle Aged ; Neutrophils - drug effects ; Neutrophils - metabolism ; Oxidative Stress ; Pharmacology. Drug treatments ; Superoxides - blood</subject><ispartof>Clinical endocrinology (Oxford), 2002-04, Vol.56 (4), p.449-455</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4333-440ff94bb99d904fe5e3966c15bafb62aca3b9e33ac33a07444a5c20f61629783</citedby><cites>FETCH-LOGICAL-c4333-440ff94bb99d904fe5e3966c15bafb62aca3b9e33ac33a07444a5c20f61629783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13777981$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11966737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smith, J. C.</creatorcontrib><creatorcontrib>Lang, D.</creatorcontrib><creatorcontrib>McEneny, J.</creatorcontrib><creatorcontrib>Evans, L. M.</creatorcontrib><creatorcontrib>Scanlon, M. F.</creatorcontrib><creatorcontrib>Young, I.</creatorcontrib><creatorcontrib>Davies, J.</creatorcontrib><title>Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description><![CDATA[Summary
objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated with adult GHD.
design and patients In a randomized, double‐blind, placebo‐controlled study we investigated the effects of GH replacement on low‐density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age‐ and sex‐matched healthy controls were also studied.
measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper‐catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin‐based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.
results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P < 0·01) and higher triglyceride concentrations (2·3 ± 1·5 vs. 1·1 ± 0·7 mmol/l, P < 0·001) but lower HDL cholesterol (1·1 ± 0·3 mmol/l vs. 1·4 ± 0·4 mmol/l, P < 0·01), lower levels of HPOs (0·72 ± 0·35 vs. 0·92 ± 0·20 µm, P < 0·01) and lower basal (2·5 ± 1·5 vs. 4·5 ± 2·3 mV/5 × 105 neutrophils, P < 0·01) and peak post‐activation levels (23·2 ± 11·1 vs. 34·4 ± 15·6 mV/5 × 105 neutrophils, P < 0·01) of neutrophil O2− generation. GH replacement resulted in an increase in HPOs from 0·70 ± 0·39 to 0·86 ± 0·19 µm (P < 0·05), although there was no change in the lag time of LDL oxidation. Neutrophil O2− generating capacity was enhanced with a rise in basal O2− generation from 2·8 ± 1·4 to 5·4 ± 4·6 mV/5 × 105 neutrophils (P < 0·05) and in peak post‐activation O2− generation from 21·9 ± 9·5 to 35·8 ± 21·7 mV/5 × 105 neutrophils (P < 0·05). LDL cholesterol was reduced from 4·1 ± 0·8 mmol/l to 3·5 ± 0·8 mmol/l (P < 0·01). No significant changes in measured parameters occurred in the placebo group.
conclusions Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O2− generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro‐atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte–lipoprotein interactions.]]></description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Hormones. Endocrine system</subject><subject>Human Growth Hormone - deficiency</subject><subject>Human Growth Hormone - pharmacology</subject><subject>Human Growth Hormone - therapeutic use</subject><subject>Humans</subject><subject>Hypopituitarism - blood</subject><subject>Hypopituitarism - physiopathology</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Lipoproteins, LDL - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>Oxidative Stress</subject><subject>Pharmacology. Drug treatments</subject><subject>Superoxides - blood</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNqNkE-P1CAYxonRuOPqVzBc9NYKhdLh4MGM46zJZjRG45FQ-rLD2KEV2uz06ieXOs3u1QOB8Pye98-DEKYkp4SLd8ecMlFmRSHKvCCkyAnlkuXnJ2j1IDxFK8IIyYgQ_Aq9iPFICCnXpHqOriiVQlSsWqE_W2vBDBF3Fu9ucOdx63rX4B5Cd3aNHlz60r7BHsYhdP3BtTiOiwpJSXp2Bx5CQv0dNrrXxg0Tdh4fpr7r3TC6QYcJ62ZsU597NxzmTg1YZxx4M71Ez6xuI7xa7mv049P2--Ymu_2y-7z5cJsZzhjLOCfWSl7XUjaScAslsLSFoWWtbS0KbTSrJTCmTTqk4pzr0hTECioKWa3ZNXp7qduH7vcIcVAnFw20rfbQjVFVVPBSljO4voAmdDEGsKoP7pR2UJSoOX91VHPMao5Zzfmrf_mrc7K-XnqM9QmaR-MSeALeLICORrc2aG9cfORYVVVyTRP3_sLduxam_x5Abbb7-ZX82cXv4gDnB78Ov9Q8R6l-7neK7XcfJf32VTH2F9kWsi8</recordid><startdate>200204</startdate><enddate>200204</enddate><creator>Smith, J. C.</creator><creator>Lang, D.</creator><creator>McEneny, J.</creator><creator>Evans, L. M.</creator><creator>Scanlon, M. F.</creator><creator>Young, I.</creator><creator>Davies, J.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200204</creationdate><title>Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency</title><author>Smith, J. C. ; Lang, D. ; McEneny, J. ; Evans, L. M. ; Scanlon, M. F. ; Young, I. ; Davies, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4333-440ff94bb99d904fe5e3966c15bafb62aca3b9e33ac33a07444a5c20f61629783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Hormones. Endocrine system</topic><topic>Human Growth Hormone - deficiency</topic><topic>Human Growth Hormone - pharmacology</topic><topic>Human Growth Hormone - therapeutic use</topic><topic>Humans</topic><topic>Hypopituitarism - blood</topic><topic>Hypopituitarism - physiopathology</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Lipoproteins, LDL - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>Oxidative Stress</topic><topic>Pharmacology. Drug treatments</topic><topic>Superoxides - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, J. C.</creatorcontrib><creatorcontrib>Lang, D.</creatorcontrib><creatorcontrib>McEneny, J.</creatorcontrib><creatorcontrib>Evans, L. M.</creatorcontrib><creatorcontrib>Scanlon, M. F.</creatorcontrib><creatorcontrib>Young, I.</creatorcontrib><creatorcontrib>Davies, J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, J. C.</au><au>Lang, D.</au><au>McEneny, J.</au><au>Evans, L. M.</au><au>Scanlon, M. F.</au><au>Young, I.</au><au>Davies, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2002-04</date><risdate>2002</risdate><volume>56</volume><issue>4</issue><spage>449</spage><epage>455</epage><pages>449-455</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract><![CDATA[Summary
objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated with adult GHD.
design and patients In a randomized, double‐blind, placebo‐controlled study we investigated the effects of GH replacement on low‐density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age‐ and sex‐matched healthy controls were also studied.
measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper‐catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin‐based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.
results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P < 0·01) and higher triglyceride concentrations (2·3 ± 1·5 vs. 1·1 ± 0·7 mmol/l, P < 0·001) but lower HDL cholesterol (1·1 ± 0·3 mmol/l vs. 1·4 ± 0·4 mmol/l, P < 0·01), lower levels of HPOs (0·72 ± 0·35 vs. 0·92 ± 0·20 µm, P < 0·01) and lower basal (2·5 ± 1·5 vs. 4·5 ± 2·3 mV/5 × 105 neutrophils, P < 0·01) and peak post‐activation levels (23·2 ± 11·1 vs. 34·4 ± 15·6 mV/5 × 105 neutrophils, P < 0·01) of neutrophil O2− generation. GH replacement resulted in an increase in HPOs from 0·70 ± 0·39 to 0·86 ± 0·19 µm (P < 0·05), although there was no change in the lag time of LDL oxidation. Neutrophil O2− generating capacity was enhanced with a rise in basal O2− generation from 2·8 ± 1·4 to 5·4 ± 4·6 mV/5 × 105 neutrophils (P < 0·05) and in peak post‐activation O2− generation from 21·9 ± 9·5 to 35·8 ± 21·7 mV/5 × 105 neutrophils (P < 0·05). LDL cholesterol was reduced from 4·1 ± 0·8 mmol/l to 3·5 ± 0·8 mmol/l (P < 0·01). No significant changes in measured parameters occurred in the placebo group.
conclusions Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O2− generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro‐atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte–lipoprotein interactions.]]></abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11966737</pmid><doi>10.1046/j.1365-2265.2002.01493.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences Double-Blind Method Female Hormones. Endocrine system Human Growth Hormone - deficiency Human Growth Hormone - pharmacology Human Growth Hormone - therapeutic use Humans Hypopituitarism - blood Hypopituitarism - physiopathology Lipid Peroxidation - drug effects Lipoproteins, LDL - blood Male Medical sciences Middle Aged Neutrophils - drug effects Neutrophils - metabolism Oxidative Stress Pharmacology. Drug treatments Superoxides - blood |
| title | Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency |
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