Physiology最新文献

{"title":"Physiological Knowledge Loss in Fourth-Year Nursing Students","authors":"Raj Narnaware, Sharlini Purani, M. Neumeier","doi":"10.1152/physiol.2024.39.s1.2307","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2307","url":null,"abstract":"There is a growing concern that nursing students struggle to retain adequate physiological knowledge throughout their program to meet their entry to practice competencies. However, how much and what knowledge is lost and when this occurs over a four-year undergraduate Bachelor of Science in Nursing program remains to be evaluated. Moreover, physiological knowledge retention has not been studied as extensively as anatomical knowledge retention in health care disciplines, including nursing programs (Narnaware, Y., 2021). Most of these studies are conducted after graduation (Aari et al., 2004) or focused on very limited systems (Pourshanazari et al., 2013). The present study aims to evaluate the level of physiological knowledge loss by nursing students in the fourth year between completing their physiology course in first-year nursing and fourth-year Critical Care nursing course . To evaluate physiological knowledge loss in the fourth year, nursing students were quizzed on ten organ systems using the online quizzing platform- Kahoot. Approximately nine to eleven knowledge and comprehension-level multiple-choice questions were delivered via kahoot. Then, these scores were compared to first-year quiz scores on the same content to determine overall knowledge loss over three years. Using SPSS II, the data was analyzed, and means were compared using 2-sample t-tests. The scores are described for each organ system by reporting the mean and standard deviation (±SD) with statistical significance set at P < 0.05 for all tests. The mean score of questions from all organ systems in year one was 62.89 ± 10.49 (±SD). Comparing that score to matched test items evaluated in the Critical Care course, there is a decrease in the overall mean score from 62.89 ± 10.49 (±SD) to 47.69 ± 8.23 (±SD). This equates to a 15.2% knowledge loss or 84.8% retention rate within three years. Organ-specific knowledge loss was highest for fluid and electrolytes (30.7%), hormones (28.6%), defences (22.5%), and reproductive physiology (22.5%), followed by renal physiology (19.7%). Knowledge loss was comparatively lower for blood (15.9%), inflammation (11.2%), vascular (7.5%) and respiratory physiology (4.7%). However, this loss was lowest for digestive physiology (-3.7%). The results of this study demonstrate a lower level of knowledge loss overall, with variations in loss being system-specific. The level of knowledge loss in the present study was significantly lower than previously reported in medical and allied health students (Pourshanazari et al., 2013) and lowest than anatomical knowledge retention levels in the same population (Narnaware and Neumeier, 2021). However, compared to the third year, knowledge loss in the fourth year is not significantly different (Narnaware et al., 2021). Applied for Teaching Physiology Section- Travel Fellowship Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Interleukin-6 in Regulating Glomerular Filtration Rate during Angiotensin II and High Salt Conditions","authors":"Mark Hatcher, Rong Duan, Dexter Lee","doi":"10.1152/physiol.2024.39.s1.1923","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1923","url":null,"abstract":"Previous results demonstrate that interleukin-6 (IL-6) increases mean arterial pressure (MAP) during Angiotensin II (Ang II)-salt hypertension. In addition, albumin excretion was lower in IL-6 knockout mice (KO) when compared to wild-type (WT). This study investigated the role of IL-6 on regulating glomerular filtration rate (GFR), renal plasma flow (RPF) and MAP in WT and IL-6 KO mice treated with a slow pressor dose of Ang II (200 ng/kg/min) +/- 6% high-salt (HS) diet. Male C57BL6 and IL-6 KO mice (12 weeks old) were treated with Ang II +/- 6% HS diet for 12 – 14 days. Mean arterial pressure, RPF and GFR were measured in anesthetized mice. MAP was 130 ± 7 mmHg and 91 ± 4 mmHg in control WT and IL-6 KO mice, respectively. Ang II treatment increased MAP in WT (153 ± 5 mmHg) and no change in IL-6 KO (83 ± 4 mmHg) mice. Ang II + 6% HS increased MAP to 150 ± 11 mmHg in WT and 93 ± 4 mmHg in IL-6 KO mice. Baseline RPF was 1822 ± 229 and 1912 ± 402 ml/min/g in control WT and IL-6 KO mice, respectively. Ang II treatment increased RPF in WT (3156 ± 753 ml/min/g), while lowering RPF in IL-6 KO (1648 ± 422 ml/min/g) mice. RPF during Ang II + 6% HS treatment was decreased in WT (1095 ± 305 ml/min/g) and IL-6 KO (1133 ml/min/g) mice. GFR was 756 ± ml/min/g and 788 ± ml/min/g in control WT and IL-6 KO mice, respectively. Ang II increased GFR in WT (1009 ± 63 ml/min/g) and no change in IL-6 KO (756 ± 23 ml/min/g). Ang II + 6% HS increased GFR in WT (1095 ± 146 ml/min/g) and no change in GFR of IL-6 KO (540 ± 207 ml/min/g) mice. Our results suggest that IL-6 reduces MAP during baseline, Ang II, and Ang II + 6% HS. The absence of IL-6 prevented increases in MAP, RPF and GFR during Ang II treatment. Our data also suggest that IL-6 contributes to increased MAP and GFR during Ang II + 6% HS treatment. K01HL092593-05. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of pulmonary artery mechanical testing","authors":"Mahin Gadkari, K. Suresh, Lakshmi Santhanam","doi":"10.1152/physiol.2024.39.s1.746","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.746","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is an incurable disease with mortality within 3 years in 28-55% of high-risk patients. The progression of PAH has been known to be associated with increased vascular stiffness and vascular remodeling. Recent studies have suggested that increased stiffness may in fact be a driver for some of the metabolic abnormalities observed during PAH. To gain more insights into this relationship, we need to quantify the differences in mechanical properties of healthy and hypertensive pulmonary arteries. The stress-strain relationship is the gold standard for the ex-vivo stiffness measurement of arteries. This is obtained by obtaining force vs. distension data by tensile testing and using sample dimensions, i.e. length, lumen diameter, and wall thickness, to calculate engineering stress and strain. While this approach is well-optimized for large muscular arteries, it has not been used to test pulmonary arteries as their thin walls and low basal tone make it challenging to make precise measurements of sample wall thickness and lumen diameter. Thus, the goals of this study were to: 1) establish a reliable protocol for rat pulmonary artery tensile testing and 2) quantify the differences in stiffness between hypertensive and healthy pulmonary arteries. First, a methodology to improve the fidelity of determining the lumen diameter and wall thickness was developed. Using this approach, we observed that the modulus was negatively correlated with the length of the vessel segment tested. This suggests that vessel length should be standardized to perform reliable comparisons between groups. Next, we performed tensile tensing on both control and hypertensive pulmonary arteries, after standardizing vessel segment lengths. We initially modeled this tensile testing data using a one-term exponential equation and we observed that intact hypertensive arteries were ~2.7 times stiffer than control arteries at low strain (strain = 0.8). Whereas at high strain (strain = 2.8) intact and decellularized hypertensive arteries were 20 and 29 times stiffer than control arteries respectively. To better capture the viscoelastic properties of both, the cellular and ECM components of the vessels we also fit the tensile testing data using a two-term exponential equation. Using this two-term exponential model, we observed that hypertensive vessels were 2.2 times stiffer than the controls at normal hoop stress (20 kPa), and at the hypertensive hoop stress (66 kPa) the diseased vessels showed less variability in stiffness as compared to the controls. These findings and the methods developed in this study will be helpful in conducting and analyzing experiments to investigate the relationship between changes in biomechanical signals and the progression of PAH. R01HL151530 (KS), R01HL126514 (LS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additiona","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141138629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breath-by-breath Analysis of a Rat Model of Pompe Disease Exposes Deficits in High-frequency Behaviors","authors":"Alyssa Mickle, Sabhya Rana, Ethan S. Benevides, Barry Byrne, David D. Fuller, Erica Dale","doi":"10.1152/physiol.2024.39.s1.901","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.901","url":null,"abstract":"Pompe disease (PD) is caused by a loss of function of the enzyme acid-α-glucosidase (GAA) leading to glycogen accumulation, neuromuscular dysfunction, and breathing failure. Here, we characterized longitudinal changes in breathing of GAA null ( Gaa−/−) rats on a breath-by-breath basis using a novel respiratory event detection algorithm. Adult Pompe (n = 5) and Sprague Dawley (n = 5) rats were implanted with chronic diaphragm EMG electrodes. Once a month from 4-10 months of age, full body plethysmography with concurrent EMG was used to record respiratory waveforms under room air and hypoxia. Waveforms were analyzed by the Adjustable Baselines Respiratory Analysis Program (ABRAP) algorithm. An adaptive threshold identified “respiratory events” defined as crossings of a threshold set between the recent maxima and minima of the waveform. After event identification, a range of waveform characteristics are calculated and tagged to that event. Averages of each characteristic were taken for all events and then analyzed based on respiratory rate in breaths/minute (bpm): low (<120 bpm, ‘quiet breathing’), medium (between 120 and 240 bpm) and high (>240 bpm, ‘high frequency sniffng’). In room air, Pompe rats had a lower breathing rate than wildtype rats by month 10 (173 vs 285 bpm, standard error of the difference (SE of diff.) 37, p=0.03). This decrease in frequency was driven by the high rate events as there were no differences in the mean rate of low rate events at month 10 (80 vs 83 bpm, SE of diff. 3) while the frequency of high rate events was significantly lower by 9 months (mo 9: 393 vs 440 bpm, SE of diff. 16, p=0.04, mo 10: 383 vs 440 bpm, SE of diff. 17, p=0.008). Not only was the breathing frequency of high-rate events impaired in Pompe rats, but there was a trend towards decrease in the proportion of events falling in the high rate category indicating less time spent in high rate breathing behaviors (mo 4: 52 vs 59%, SE of diff. 6, mo 10: 25 vs 52%, SE of diff. 9) with a concomitant increase in the proportion of low frequency events. Additionally, there was a main effect of genotype on the latency between diaphragm activation and onset of inspiratory flow during hypoxia with Pompe rats having a longer latency across all months and frequency bands. This difference was most pronounced in the medium (44 vs 29 ms, SE of diff. 4 ms, p=0.003) frequency events. Active expiration was impaired in Pompe animals with peak post-event airflow (maximum positive pressure reached before the next inspiratory effort) blunted across all months. This effect was pronounced in the high frequency events (0.16 mL vs 0.24 mL, SE of diff. 0.01, p=0.0001). These deficits in high frequency events are consistent with progressive neuromuscular diaphragm weakness. We conclude that comprehensive analyses of all respiratory events over extended recording periods enables detection of altered breathing behaviors that may be missed when assessing only short periods of quiet breat","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141143001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Dependent Regulation of Mucin Gene Transcription and Goblet Cell Secretion Machinery Following Intra-Airway IL-13 in Mice with Conditional Loss of Club Cell Creb1","authors":"Mariana Sponchiado, Amy Fagan, Luz Mata, Angelina L. Bonilla, Pedro Trevizan Bau, Sreekala Prabhakaran, Leah R. Reznikov","doi":"10.1152/physiol.2024.39.s1.2053","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2053","url":null,"abstract":"IL-13 is an important effector molecule in allergic asthma, converting secretoglobin-positive club cells into mucin-secreting goblet cells and promoting mucin hypersecretion. IL-13-mediated conversion of club cells to goblet cells requires decreased gene expression of forkhead box A2 ( FOXA2) and increased gene expression of SAM pointed domain containing ETS transcription factor ( SPDEF). In addition, IL-13-mediated mucin hypersecretion may include modulation of purinergic and muscarinic receptors that control basal and stimulated mucus secretion, respectively. We recently found that the cAMP response element-binding protein (CREB), a ubiquitous transcription factor, directly binds to FOXA2 and modulates mucus secretion mechanisms in mice. Here we tested the hypothesis that conditional loss of club cell Creb1 in murine airways modulates the pro-mucin effects of IL-13. Loss of club cell Creb1 augmented IL-13-mediated increases in gene expression of the major gel-forming secreted mucins Muc5ac and Muc5b in male murine airways, with no effect on IL-13-mediated increases in Muc5ac and Muc5b in female murine airways. Examination of mucin secretion mechanisms revealed that IL-13 decreased muscarinic 3 receptor ( M3R) mRNA expression in male murine airways, whereas loss of club cell Creb1 prevented this, resulting in a significant treatment by genotype interaction. Interestingly, in female airways, a main effect of genotype was observed, with loss of club cell Creb1 reducing M3R mRNA expression in the airway. Examination of the purinergic receptor P2Y ( P2ry2) mRNA revealed a main treatment effect for IL-13 to increase P2ry2 expression in male murine airways with no impact of loss of club cell Creb1. In the females, IL-13 increased P2ry2 mRNA in both genotypes, with loss of club cell Creb1 significantly blunting the effect of IL-13 on P2ry2 mRNA. Lastly, we examined goblet cell density and mucin secretion mechanisms using Alcian Blue-PAS staining post in vivo stimulation with a muscarinic agent. We found no major effect of treatment or genotype in the density of goblet cells containing acidic mucins in either male or female airways. In contrast, both males and females showed IL-13-mediated increases in the density of goblet cells containing neutral mucins that was not impacted by genotype. Our preliminary findings suggest that loss of club cell Creb1 decreases molecular mucin secretion mechanisms in male and female airways, and increases Muc5ac and Muc5b mRNA in male airways, though a corresponding genotype-dependent increase in goblet cell density post cholinergic stimulation was not observed. Thus, we conclude that loss of club cell Creb1 causes changes to molecules important for IL-13-mediated mucin hypersecretion, without apparent functional benefit or detriment to the murine airway. This work was supported by the National Institutes of Health (OD026582, HL152101), the Cystic Fibrosis Foundation (REZNIKO20I0, REZNIKO19I0), the Katie Rose Foundation ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing, Chronic Stress Exposure Is Related to Impaired Vascular Endothelial Function Among Young Adults Irrespective of Subjective Appraisal of Stressor Severity","authors":"Alyssa S. Carlson, Laura E. Schwager, Sara Diesel, Jenna Adamowicz, Jordan Harris, Mark Flores, E. Thomas","doi":"10.1152/physiol.2024.39.s1.712","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.712","url":null,"abstract":"Introduction: Chronic stress is associated with cardiovascular morbidity independently of traditional cardiovascular risk factors. Vascular endothelial function (VEF) is predictive of cardiovascular risk and is reduced in response to transient and chronic psychosocial stress. While dominant stress theories (i.e., differential exposure model) posit that stress exposure explains health disparities, it has also been hypothesized that the subjective experience of these stressors — or stress appraisal — may also influence the effects of stress exposure on health. The purpose of this study was to investigate the associations of ongoing, chronic stress exposure and stress appraisal on VEF in young adults. Our hypothesis was that ongoing, chronic stress exposure, rather than stress appraisal, would be more strongly and inversely associated with VEF. We further conceptualized that stress appraisal would moderate the association between stress exposure and VEF. Methods: In 64, healthy young adults (75% Female; age = 25 ± 5 y), we assessed cumulative, chronic stress exposure with a measure that quantified ongoing exposure to 8 specific stressors over the last 12 months. For each chronic stress exposure reported, participants rated the perceived stressor severity using a 3-point Likert scale ( 1 = not upsetting, 2 = somewhat upsetting, 3 = very upsetting). The number of stressors was used as the indicator of ongoing, chronic stress exposure, while the average stressor severity was used as the indicator of stress appraisal. We assessed VEF using the brachial artery flow mediated dilation (FMD) technique normalized to the shear rate stimulus (%·[s1×10−2]) quantified as shear rate area under the curve. Using partial correlations, we examined relations among ongoing, chronic stress exposure and stress appraisal versus VEF, independently of sex. We then conducted an exploratory moderation analysis to assess whether stress appraisal moderated the effect of ongoing, chronic stress exposure on VEF. Results: Ongoing, chronic stress exposure (r=-0.32, p<0.05), but not stress appraisal (r=-0.13, p=0.34) was related to VEF. Further, stress appraisal did not significantly moderate the association between ongoing, chronic stress exposure and VEF (p=0.69). However, the direct effect of ongoing, chronic stress exposure was statistically significant (β = -0.51; p=0.009), whereas the effect of stress appraisal was not (p=0.79), confirming our initial correlation analyses. Conclusions: Our findings indicate that ongoing, chronic stress exposure, rather than the subjective appraisal of this stress, significantly predicts impaired vascular endothelial function among young adults. Thus, our findings provide initial evidence indicating that stressor exposure is suffcient to increase cardiovascular risk independently of the perceived severity of the stressor(s) among young adults. However, the strength of our moderation analysis is limited by sample size, and future larger-scale st","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial function in lungs of rats with different susceptibilities to hyperoxia-induced Acute Respiratory Distress Syndrome (ARDS)","authors":"Pardis Taheri, Ranjan Dash, Devanshi Dave, Anne Clough, E. Jacobs, Said Audi","doi":"10.1152/physiol.2024.39.s1.969","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.969","url":null,"abstract":"Objective: Rat exposure to hyperoxia is a well-established model of human ARDS. Adult rats exposed to hyperoxia (100% O2) die from respiratory failure within 60-72 hours. However, rats preconditioned by exposure to >95% O2 for 48 hrs followed by a 24-hr “rest period” in room air (H-T) acquire tolerance of the otherwise lethal effects of exposure to 100% O2. In contrast, rats preconditioned by exposure to 60% O2 for 7 days (H-S) become more susceptible to 100% O2. The objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Methods: Adult rats were exposed to room air (normoxia), >95% O2 for 48 hrs followed by exposure to room air for 24 hrs (H-T), or 60% O2 for 7 days (H-S). Mitochondria were isolated from lung tissue and used to assess mitochondrial bioenergetics. Expressions of electron transport chain complexes were measured in lung tissue homogenate using western blot. Isolated perfused lungs (IPL) were used to determine pulmonary vascular endothelial filtration coeffcient ( Kf) as a measure of pulmonary vascular permeability, and lung tissue mitochondrial membrane potential (ΔΨm). Results: Western blot shows decreased (38%) complex I expression, but increased (70%) complex V expression in H-T lung tissue homogenate compared to normoxia. Complex I expression decreased (43%) in H-S lung tissue homogenate. State 3 oxidative phosphorylation (OxPhos) capacity (Vmax) and respiratory control ratio decreased in mitochondria isolated from H-S lungs. Vmax increased in mitochondria of H-T lungs. Time for ΔΨm repolarization following ADP-stimulated depolarization increased in mitochondria isolated from H-S lungs. IPL studies revealed that tissue ΔΨm is unchanged in H-S and H-T lungs compared to normoxics. Furthermore, complex I plays the dominant role in ΔΨm in H-T and normoxia lungs with no contribution from complex II, whereas complex II has a larger contribution to ΔΨm in H-S lungs than in H-T or normoxia. Kf increased (+178%) in H-S, but not H-T lungs. Discussion: For H-T lungs, decreased complex I expression is countered by increased complex V expression, which could also account for increased Vmax. This along with high tissue glutathione content protects mitochondria from stress such as exposure to 100% O2. For H-S lungs, the effect of decreased complex I expression on lung tissue ΔΨm is countered by a larger contribution from complex II. However, higher dependency of ΔΨm on complex II could lead to higher mitochondrial oxidant production since complex II is the main source of oxidants in rat lungs. This along with decreased Vmax and increased Kf make H-S rats more susceptible to stress such as exposure to 100% O2. These results are clinically relevant since exposure to hyperoxia is a primary therapy for patients with ARDS, and ventilation with 60% O2 is often required for prolonged periods of time, particularly with COVID-19. This study was funded by NHLBI grant 2R15HL129209-03, Department of Veterans Affairs Merit R","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent ethanol vapor exposure enhances ferroptosis following repeated mild traumatic brain injury in the frontal lobe of adolescent rats; potential role of mitochondrial dysregulation","authors":"Xavier Chapa, Sydney Vita, Nick Gilpin, Scott Edwards, Liz Simon, Patricia Molina","doi":"10.1152/physiol.2024.39.s1.2038","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2038","url":null,"abstract":"Adolescents involved in sports have increased risk of traumatic brain injuries (TBI), and frequently participate in binge alcohol consumption in comparison to non-athletic peers. Recovery from a TBI requires substantial energy, and effcient metabolic activity, which depend on intact mitochondria structure and function. Alcohol impairs mitochondrial function, including mitochondrial dynamics and metabolism); that may ultimately lead to cell death. Among cell death pathways, the iron-dependent programmed cell death known as ferroptosis; which has been shown to be predominant in TBI is especially sensitive to changes in mitochondrial energy production. Whether alcohol affects TBI-associated alterations in mitochondrial function and promotes ferroptosis is not known. The aim of this study was to determine how alcohol contributes to repeated-mild TBI (rmTBI)-induced alterations in mitochondrial function (dynamics & metabolism) and ferroptosis signaling in the prefrontal cortex of adolescent male rats. Adolescent male Wistar rats were randomly assigned to i) Sham + Air (control), ii) Sham + ethanol (EtOH), iii) rmTBI + Air, or iv) rmTBI + EtOH. Starting on postnatal day 45, the animals received 3 days of intermittent EtOH vapor exposure (14 hrs on/10 hrs off). Twenty-four hours after the final EtOH exposure, animals were given an mTBI or sham procedure. This sequence was repeated for four cycles. Seven days after the final rmTBI, animals were euthanized, and brains excised for analysis, specifically the frontal lobe. Our preliminary results demonstrate that mitochondrial fusion protein, OPA1, expression was not altered in the PFC by either rmTBI or by EtOH exposure alone. However, rmTBI+EtOH resulted in a significant increase in OPA1 expression. EtOH exposure produced a significant increase in COX-IV (a subunit of ETC complex IV) expression. However, COX-IV expression was not significantly different between rmTBI or rmTBI + EtOH and controls. Mitochondrial complex I activity was not altered by rmTBI, EtOH, or rmTBI + EtOH. Expression of transferrin receptor (TfR1), a specific marker of ferroptosis was significantly increased by rmTBI and EtOH this effect was further exacerbated in the rmTBI + EtOH group. Overall, our study shows that the combination of rmTBI with EtOH exposure affects OPA1-mediated mitochondrial fusion. Additionally, exposure to EtOH increases complex IV expression. Moreover, both rmTBI and EtOH exposure independently triggered signaling pathways associated with ferroptosis, and this effect was synergistically increased when with rmTBI+ EtOH. These findings underscore the intricate interplay between EtOH exposure and rmTBI, influencing crucial mitochondrial proteins and markers of ferroptosis in the frontal lobe of the adolescent rat brain. Further research is needed to fully comprehend the underlying mechanisms and implications of these observations. This research was supported by NIH/NIAAA R01 AA025792 (PEM, NWG) & T32 AA007577 (PEM)","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone Supplementation Improves the Maternal Syndrome of Superimposed Preeclampsia in the Dahl Salt Sensitive Rats","authors":"Christy Chambers, Michael Franks, Ariel Harrell, N. Campbell, Sarah Safir, T. Turner, Jan M. Williams","doi":"10.1152/physiol.2024.39.s1.1358","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1358","url":null,"abstract":"Introduction: Preeclampsia (PE) is characterized by new onset of hypertension after 20 weeks of gestation. It affects 5-7% of all pregnancies in the U.S., and is associated with reduced fetal weight, inflammation and hypertension (HTN). Importantly, 30% of HTN disorders in pregnancy are caused by chronic HTN that is present prior to pregnancy which increases the risk of superimposed PE (SIPE). The mechanisms responsible for the pathogenesis of PE and SIPE are unclear and currently the only treatment is early delivery of the fetus. Progesterone is important for the establishment and maintenance of pregnancy. We have previously shown that progesterone supplementation with 17-hydroxyprogesterone caproate (17-OHPC) improves inflammation, fetal weight and blood pressure in the preclinical RUPP rat model of PE, however the mechanism for this in SIPE is still unknown. Hypothesis: This study was designed to test the hypothesis that 17-OHPC reduces inflammation while improving maternal blood pressure in the preclinical pregnant Dahl Salt Sensitive (DS) rat model of SIPE. Methods: 17-OHPC (3.32mg/kg) or vehicle (Saline) was administrated intraperitoneally on gestation day (GD) 15 to normal pregnant (NP) Sprague-Dawley (SD) and pregnant Dahl Salt Sensitive (DS) rats. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Vevo Doppler Ultrasound and carotid catheters were inserted. On GD 19, mean arterial blood pressure (MAP) and samples were collected. All data are expressed as mean ± standard error means (SEM). Results: MAP was 105±5 mmHg in SD+ Saline rats (n=7) and 105±4 mmHg in SD+17-OHPC rats (n=4), 137±3 mmHg in DS + Saline rats (p<0.05, n=11), which improved to 125±4 mmHg in DS+17-OHPC rats (p<0.05, n=7). Pup and Placenta weights were 2.1± 0.1 g, 0.6 ± 0.1 g in SD + saline rats and significantly reduced to 1.4±0.1 g, 0.5±0.1 g in DS+ Saline rats (p<0.05). Neither placental weight nor pup weight was affected by 17-OHPC. UARI was 0.5 ±0.1 in SD+ Saline rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=4), 0.7±0.1 in DS+Saline rats (n=6, p<0.05), which reduced to 0.5±0.1 in DS+17-OHPC (n=7, p<0.05). TNF-alpha levels were 3.0±1.0 pg/mL in SD+ Saline rats, 11.0±1.2 in DS + Saline rats, which reduced to 4.1±1.6 in DS+17-OHPC (n=4, p<0.05). Importantly, circulating and placental CD4+ T cells were 9.3±3.7 % Gate and 6.4± 1.6 % Gate in SD+ Saline rats (n=4), 38.9 ±2.9 % Gate and 33.1±4.3 % Gate in DS + Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 % Gate and 3.4±1.2 % Gate in DS + 17-OHPC. Conclusion: Collectively, our findings demonstrate that 17-OHPC reduces inflammation and hypertension in the Dahl Salt Sensitive rat model of SIPE. Supported by NIH P20GM121334. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Circulating Extracellular Vesicles from Adults with Spinal Cord Injury on Pulmonary Artery Endothelial Cell Function","authors":"Samuel T. Ruzzene, Hannah K. Fandl, Hannah L. Cardenas, Vinicius P. Garcia, Jared James Greiner, A. J. Park, Christopher A. DeSouza","doi":"10.1152/physiol.2024.39.s1.1951","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1951","url":null,"abstract":"Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. Despite an improved understanding of the neurological and physical consequences associated with SCI, factors that initiate, promote and accelerate cardiopulmonary disease are poorly understood. It has become apparent that the increased incidence of pulmonary disorders in adults with chronic SCI is not solely due to worsening of traditional risk factors, but also involves ill-defined factors. Several studies have implicated circulating endothelial cell-derived microvesicles (EMVs) in the etiology of cardiopulmonary diseases. We have previously reported that circulating EMVs are elevated in adults with chronic SCI and the expression of their microRNA cargo promotes disease. Reduction in pulmonary nitric oxide (NO) bioavailability and increased endothelin (ET)-1 production underly many cardiopulmonary disorders associated with SCI. The experimental aim of this study was to determine the effect of EMVs isolated from adults with chronic tetraplegic SCI on pulmonary endothelial cell NO and ET-1 production. As part of an ongoing study, circulating EMVs (CD144-PE) were isolated (flow cytometry) from 7 non-injured adults (all male; age: 38±4 yr) and 7 motor complete SCI adults with tetraplegic SCI (male; 44±5 yr). All subjects were free of overt cardiometabolic disease. Human pulmonary artery endothelial cells (HPAECs) were cultured and separately treated with EMVs from each subject for 24 hr. Expression of intracellular NO and ET-1 proteins of interest was determined by capillary electrophoresis immunoassay. Circulating EMV concentrations were significantly higher (~200%) in SCI vs non-injured (154±36 vs 54±7 EMV/μL). Expression of p-eNOS (Ser1177), the primary activation site for eNOS, was ~30% lower (96.0±2.3 vs 140.7±8.9 AU; p<0.01) and p-eNOS (Thr495), primary inhibitory site, ~40% higher (40.7±1.7 vs 28.8±3.1 AU; p<0.01) in cells treated with EMVs from SCI vs non-injured. As a result, NO production was ~20% lower (6.5±0.3 vs 8.3±0.7 μmol/L; P=0.03) in HPAECs treated with EMVs from adults with SCI. SCI-associated EMVs also significantly increased (~70%) the expression of Big ET-1 (60.6±3.6 vs 36.1±2.7 AU) resulting in enhanced endothelial ET-1 production (884.0±22.9 vs 778.7±18.0 pg/mL). In conclusion, EMVs harvested from adults with SCI markedly reduced eNOS activation and NO production and increased ET-1 synthesis and release in pulmonary endothelial cells in vitro. Circulating EMVs represent a potential mechanistic factor underlying pulmonary disorders and increased disease risk with SCI. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}