Publications by authors named "Patrice Rosengrave"

12 Publications

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Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis.

Free Radic Biol Med 2021 Nov 21. Epub 2021 Nov 21.

Department of Pathology and Biomedical Science, University of Otago, Christchurch, PO Box 4345, Christchurch, 8140, New Zealand. Electronic address:

Background: Septic shock is a life-threatening dysregulated response to severe infection and is associated with elevated oxidative stress. We aimed to assess protein carbonyls in critically ill patients with different sources of sepsis and determine the effect of vitamin C intervention on protein carbonyl concentrations.

Methods: Critically ill patients with septic shock (n = 40) were recruited, and sources of sepsis and ICU severity scores were recorded. The patients were randomised to receive either intravenous vitamin C (100 mg/kg body weight/day) or placebo infusions. Blood samples were collected at baseline and daily for up to three days for measurement of cell counts, vitamin C concentrations, protein carbonyls, C-reactive protein, and myeloperoxidase concentrations.

Results: Protein carbonyl concentrations increased 2.2-fold in the cohort over the duration of the study (from 169 to 369 pmol/mg protein; p = 0.03). There were significant correlations between protein carbonyl concentrations and ICU severity scores (APACHE III r = 0.47 and SOFA r = 0.37; p < 0.05) at baseline. At study admission, the patients with pneumonia had nearly 3-fold higher protein carbonyl concentrations relative to the patients with other sources of sepsis (435 vs 157 pmol/mg protein, p < 0.0001). The septic patients had deficient vitamin C status at baseline (9.8 ± 1.4 μmol/L). This increased to 456 ± 90 μmol/L following three days of intravenous vitamin C intervention. Vitamin C intervention did not attenuate the increase in protein carbonyl concentrations.

Conclusions: Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis. The reasons for this are currently unclear and may indicate a mechanism unique to pulmonary sources of sepsis. Intravenous vitamin C administration did not attenuate the increase in protein carbonyls over time.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.11.029DOI Listing
November 2021

Neutrophils Isolated from Septic Patients Exhibit Elevated Uptake of Vitamin C and Normal Intracellular Concentrations despite a Low Vitamin C Milieu.

Antioxidants (Basel) 2021 Oct 13;10(10). Epub 2021 Oct 13.

Department of Intensive Care Medicine, Christchurch Hospital, Private Bag 4710, Christchurch 8140, New Zealand.

Vitamin C (ascorbate) plays an important role in neutrophil function and is accumulated by the cells either directly via vitamin C transporters (SVCT) or indirectly following oxidation to dehydroascorbic acid. Septic patients are known to have significantly depleted plasma ascorbate status, but little is known about the ascorbate content of their circulating cells. Therefore, we assessed the ascorbate concentrations of plasma, leukocytes and erythrocytes from septic patients and compared these to healthy controls. Non-fasting blood samples were collected from healthy volunteers ( = 20) and critically ill patients with sepsis ( = 18). The ascorbate content of the plasma and isolated neutrophils and erythrocytes was measured using HPLC and plasma myeloperoxidase concentrations were determined using ELISA. Ex vivo uptake of ascorbate and dehydroascorbic acid by neutrophils from septic patients was also assessed. Neutrophils isolated from septic patients had comparable intracellular ascorbate content to healthy volunteers (0.33 vs. 0.35 nmol/10 cells, > 0.05), despite significantly lower plasma concentrations than the healthy controls (14 vs. 88 µmol/L, < 0.001). In contrast, erythrocytes from septic patients had significantly lower intracellular ascorbate content than healthy controls (30 vs. 69 µmol/L, = 0.002), although this was 2.2-fold higher than the matched plasma concentrations in the patients ( = 0.008). Higher concentrations of myeloperoxidase, a source of reactive oxygen species, were observed in the septic patients relative to healthy controls (194 vs. 14 mg/mL, < 0.0001). In contrast to neutrophils from healthy volunteers, the neutrophils from septic patients demonstrated elevated uptake of extracellular ascorbate. Overall, neutrophils from septic patients exhibited comparable intracellular ascorbate content to those from healthy controls, despite the patients presenting with hypovitaminosis C. The mechanisms involved are currently uncertain, but could include increased generation of dehydroascorbic acid in septic patients, enhanced basal activation of their neutrophils or upregulation of their vitamin C transporters.
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http://dx.doi.org/10.3390/antiox10101607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533547PMC
October 2021

Ovarian fluid proteome variation associates with sperm swimming speed in an externally fertilizing fish.

J Evol Biol 2020 12 25;33(12):1783-1794. Epub 2020 Oct 25.

Department of Anatomy, University of Otago, Dunedin, New Zealand.

Sperm velocity is a key trait that predicts the outcome of sperm competition. By promoting or impeding sperm velocity, females can control fertilization via postcopulatory cryptic female choice. In Chinook salmon, ovarian fluid (OF), which surrounds the ova, mediates sperm velocity according to male and female identity, biasing the outcome of sperm competition towards males with faster sperm. Past investigations have revealed proteome variation in OF, but the specific components of OF that differentially mediate sperm velocity have yet to be characterized. Here we use quantitative proteomics to investigate whether OF protein composition explains variation in sperm velocity and fertilization success. We found that OF proteomes from six females robustly clustered into two groups and that these groups are distinguished by the abundance of a restricted set of proteins significantly associated with sperm velocity. Exposure of sperm to OF from females in group I had faster sperm compared to sperm exposed to the OF of group II females. Overall, OF proteins that distinguished between these groups were enriched for vitellogenin and calcium ion interactions. Our findings suggest that these proteins may form the functional basis for cryptic female choice via the biochemical and physiological mediation of sperm velocity.
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http://dx.doi.org/10.1111/jeb.13717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719593PMC
December 2020

There and back again: A sperm's tale.

Mol Reprod Dev 2020 04 5;87(4):395-398. Epub 2020 Feb 5.

Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.

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http://dx.doi.org/10.1002/mrd.23325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317830PMC
April 2020

Circulating myeloperoxidase is elevated in septic shock and is associated with systemic organ failure and mortality in critically ill patients.

Free Radic Biol Med 2020 05 5;152:462-468. Epub 2019 Nov 5.

Department of Intensive Care, Christchurch Hospital, Christchurch, New Zealand.

Background: Neutrophils are elevated in critically ill patients during the systemic inflammatory response to trauma and sepsis. The neutrophil-derived enzyme myeloperoxidase generates reactive oxygen species which can react with host tissue resulting in cell damage and dysfunction. Thus, elevated myeloperoxidase in the circulation may be associated with adverse patient outcomes.

Methods: Circulating myeloperoxidase concentrations were measured in a cohort of 44 critically ill patients, 55% of whom were diagnosed with septic shock, and 44 healthy controls. Intensive care mortality prediction scores (SOFA, SAPS, APACHE) and ICU and hospital mortality were obtained from the patients' clinical notes. Hematological and biochemical assessments included blood cell counts, lactate, alanine transaminase, creatinine, bilirubin, C-reactive protein, and PaO. Myeloperoxidase was measured using a commercial ELISA kit and cell free DNA was detected using SytoxGreen™ fluorescence staining.

Results: Myeloperoxidase concentrations were significantly higher in critically ill patients than control samples (234 ± 30 ng/ml versus 15 ± 4 ng/ml, p < 0.001), and were elevated in septic shock relative to non-septic patients (302 ± 42 ng/ml versus 156 ± 38 ng/ml, p = 0.02), despite neutrophil counts being comparable between the two subgroups (p = 0.6). Myeloperoxidase correlated with SOFA scores in the critically ill patients (r = 0.395, p = 0.02), and with markers of tissue dysfunction and injury such as lactate (r = 0.572, p < 0.001), log alanine transferase (r = 0.392, p = 0.016) and log cell free DNA (r = 0.371, p = 0.03). The subgroup of patients with higher than mean APACHE III scores (i.e. >78, n = 16) exhibited significantly elevated myeloperoxidase concentrations in the non-survivors compared with survivors (416 ± 59 ng/ml versus 140 ± 33 ng/mL, p = 0.001). Hospital mortality for the whole cohort was 27%; mortality in the high APACHE III subgroup was 38%, and when combined with higher than mean myeloperoxidase (i.e. >234 ng/mL), mortality increased to 71%.

Conclusions: Myeloperoxidase is associated with markers of tissue injury and systemic organ failure, particularly in septic patients. The enzyme is also associated with mortality in patients with higher APACHE III scores, and thus has potential as an additional diagnostic marker to improve mortality prediction.
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http://dx.doi.org/10.1016/j.freeradbiomed.2019.11.004DOI Listing
May 2020

Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes.

Crit Care 2017 Dec 11;21(1):300. Epub 2017 Dec 11.

Department of Intensive Care Medicine, Christchurch Hospital, Private Bag 4710, Christchurch, 8140, New Zealand.

Background: Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients.

Methods: Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients' daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model.

Results: Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d).

Conclusions: Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.
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http://dx.doi.org/10.1186/s13054-017-1891-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725835PMC
December 2017

Sperm competition risk drives rapid ejaculate adjustments mediated by seminal fluid.

Elife 2017 10 31;6. Epub 2017 Oct 31.

Department of Anatomy, University of Otago, Dunedin, New Zealand.

In many species, males can make rapid adjustments to ejaculate performance in response to sperm competition risk; however, the mechanisms behind these changes are not understood. Here, we manipulate male social status in an externally fertilising fish, chinook salmon (), and find that in less than 48 hr, males can upregulate sperm velocity when faced with an increased risk of sperm competition. Using a series of sperm manipulation and competition experiments, we show that rapid changes in sperm velocity are mediated by seminal fluid and the effect of seminal fluid on sperm velocity directly impacts paternity share and therefore reproductive success. These combined findings, completely consistent with sperm competition theory, provide unequivocal evidence that sperm competition risk drives plastic adjustment of ejaculate quality, that seminal fluid harbours the mechanism for the rapid adjustment of sperm velocity and that fitness benefits accrue to males from such adjustment.
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http://dx.doi.org/10.7554/eLife.28811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669631PMC
October 2017

Cryptic female choice enhances fertilization success and embryo survival in chinook salmon.

Proc Biol Sci 2016 Mar;283(1827):20160001

Department of Anatomy, University of Otago, Dunedin, New Zealand Allan Wilson Centre for Molecular Ecology and Evolution, Department of Anatomy University of Otago, Dunedin, New Zealand.

In this study, we investigated two potentially important intersexual postcopulatory gametic interactions in a population of chinook salmon (Oncorhynchus tshawytscha): (i) the effect of female ovarian fluid (OF) on the behaviour of spermatozoa during fertilization and (ii) the effects of multilocus heterozygosity (MLH) (as an index of male quality) and female-male genetic relatedness on sperm behaviour and male fertilization success when there is sperm competition in the presence of that OF. To do this, we conducted a series of in vitro competitive fertilization experiments and found that, when ejaculates from two males are competing for access to a single female's unfertilized eggs, fertilization success was significantly biased towards the male whose sperm swam fastest in the female's OF. Embryo survival--a measure of fitness--was also positively correlated with both sperm swimming speed in OF and male MLH, providing novel evidence that cryptic female choice is adaptive for the female, enhancing the early survival of her offspring and potentially influencing her fitness.
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http://dx.doi.org/10.1098/rspb.2016.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822462PMC
March 2016

Working mothers are disadvantaged by limited funding for health research.

N Z Med J 2014 Jul 18;127(1398):138-40. Epub 2014 Jul 18.

Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch, New Zealand.

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July 2014

Proteomic analysis of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid.

PLoS One 2014 4;9(8):e104155. Epub 2014 Aug 4.

Allan Wilson Centre for Molecular Ecology and Evolution and Department of Anatomy, University of Otago, Dunedin, New Zealand.

The ovarian, or coelomic, fluid that is released with the egg mass of many fishes is increasingly found to play an important role in several biological processes crucial for reproductive success. These include maintenance of oocyte fertility and developmental competence, prolonging of sperm motility, and enhancing sperm swimming speed. Here we examined if and how the proteome of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid varied among females and then sought to examine the composition of this fluid. Ovarian fluid in chinook salmon was analyzed using 1D SDS PAGE and LC-MS/MS tryptic digest screened against Mascot and Sequest databases. We found marked differences in the number and concentrations of proteins in salmon ovarian fluid across different females. A total of 174 proteins were identified in ovarian fluid, 47 of which were represented by six or more peptides, belonging to one of six Gene Ontology pathways. The response to chemical stimulus and response to hypoxia pathways were best represented, accounting for 26 of the 174 proteins. The current data set provides a resource that furthers our understanding of those factors that influence successful egg production and fertilisation in salmonids and other species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104155PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121310PMC
November 2015

Delineating the roles of males and females in sperm competition.

Proc Biol Sci 2013 Dec;280(1772):20132047

Disentangling the relative roles of males, females and their interactive effects on competitive fertilization success remains a challenge in sperm competition. In this study, we apply a novel experimental framework to an ideally suited externally fertilizing model system in order to delineate these roles. We focus on the chinook salmon, Oncorhynchus tshawytscha, a species in which ovarian fluid (OF) has been implicated as a potential arbiter of cryptic female choice for genetically compatible mates. We evaluated this predicted sexually selected function of OF using a series of factorial competitive fertilization trials. Our design involved a series of 10 factorial crosses, each involving two ‘focal’ rival males whose sperm competed against those from a single ‘standardized’ (non-focal) rival for a genetically uniform set of eggs in the presence of OF from two focal females. This design enabled us to attribute variation in competitive fertilization success among focal males, females (OF) and their interacting effects, while controlling for variation attributable to differences in the sperm competitive ability of rival males, and male-by-female genotypic interactions. Using this experimental framework, we found that variation in sperm competitiveness could be attributed exclusively to differences in the sperm competitive ability of focal males, a conclusion supported by subsequent analyses revealing that variation in sperm swimming velocity predicts paternity success. Together, these findings provide evidence that variation in paternity success can be attributed to intrinsic differences in the sperm competitive ability of rival males, and reveal that sperm swimming velocity is a key target of sexual selection.
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http://dx.doi.org/10.1098/rspb.2013.2047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813331PMC
December 2013

Chemical composition of seminal and ovarian fluids of chinook salmon (Oncorhynchus tshawytscha) and their effects on sperm motility traits.

Comp Biochem Physiol A Mol Integr Physiol 2009 Jan 19;152(1):123-9. Epub 2008 Sep 19.

School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand.

The relationships between the compositions of ovarian, seminal fluids and sperm function are not well known in teleostean fish species. The objective of the present study was to determine the concentration of the major inorganic ions (Na(+), K(+), Ca(2+), Mg, Cl(-)), osmolality, and pH of ovarian and seminal fluid of sexually mature chinook salmon (Oncorhynchus tshawytscha), and to determine if the composition of these fluids influences sperm motility traits (swimming speed, duration of forward mobility, swimming path trajectory, and percent motility). Cation concentrations and osmolality were significantly different in the two fluids. The ionic composition of ovarian fluid differed among individual females, and also among samples collected at different times through the spawning season. Carbonate and bicarbonate were the principal buffer ions in ovarian fluid, and its viscosity was considerably greater than that of water and was shear-dependent. The duration of forward motility (longevity) of spermatozoa, swimming speed, percent motility, and path trajectory were measured using milt from 10 males activated in the ovarian fluid from 7 females whose ion concentrations were known. No significant correlations were observed between the composition of the seminal fluid and sperm traits. However, in ovarian fluid, sperm longevity was negatively correlated with variation in [Ca(2+)] and [Mg(2+)], while percent motility increased with increasing [Mg(2+)]. These observations provide a possible chemical basis for cryptic female mate choice whereby female ovarian fluid differentially influences the behaviour of sperm from different males, and thus their fertilization success.
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http://dx.doi.org/10.1016/j.cbpa.2008.09.009DOI Listing
January 2009
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