bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of N‐acetylcysteine on contractile function and protein‐thiol oxidation in skeletal muscles of mdx mice
Authors: Pinniger Gavin Jon , Assan Evanna Binti , Terrill Jessica , Arthur Peter 
Published: June 2021

Duchenne Muscular Dystrophy (DMD) is a fatal X‐linked recessive disease characterized by severe muscle weakness. We hypothesized that oxidation of skeletal muscle proteins such as myosin contributes to dystrophic muscle weakness seen in DMD boys and dystrophic mdx mice and that this muscle weakness will be attenuated by treatment with the antioxidant N‐acetylcysteine (NAC).Six week old mdx mice and non‐dystrophic, C57 mice were treated with 2% NAC in drinking water for six weeks and compared to untreated mdx and C57 mice. Grip strength and body weight were measured weekly during the treatment period. After six weeks of treatment, the 12 week old mice were anaesthetized (sodium pentobarbitone; 40 mg/kg; IP) and the extensor digitorum longus (EDL) muscles were excised for analysis of contractile function and protein thiol‐oxidation.In mdx mice, NAC treatment significantly increased normalized grip strength and maximum specific force in isolated EDL muscles (NAC = 13.1 ± 1.2 N/cm2; Untreated = 9.8 ± 0.8 N/cm2, p<0.05), and significantly reduced myosin protein‐thiol oxidation (NAC = 10.6 ± 0.8 %; Untreated = 13.7 ± 0.8 %, p<0.05). In non‐dystrophic C57 mice, NAC treatment significantly increased normalized grip strength by 36%, but had no significant effect on maximum specific force or myosin protein‐thiol oxidation in EDL muscles.These data suggest that oxidative stress contributes to contractile dysfunction in dystrophic muscle via modification of thiol groups on the contractile protein myosin. Furthermore, this muscle weakness may be ameliorated with the anti‐oxidant, NAC.
KCa channels and EETs: major contributors to cutaneous thermal hyperemia
Authors: Brunt Vienna E , Minson Christopher T 
Published: June 2021

While it is accepted NO is responsible for ~60% of the plateau in cutaneous thermal hyperemia, a large portion of the response remains unknown. We sought to determine whether the remaining ~40% could be attributed to EDHFs via KCa channels, and whether the epoxyeicosatrienoic acids (EETs), derived via cytochrome P450, were the predominant EDHF active in the response. Four microdialysis fibers were placed in the forearm skin of 20 subjects. In Protocol 1 (n=10): (1) Control, (2) L‐NAME, (3) KCa channel inhibitor, tetraethylammonium (TEA), and (4) L‐NAME + TEA; in Protocol 2 (n=10): (1) Control, (2) L‐NAME, (3) cytochrome P450 inhibitor, sulfaphenazole, and (4) L‐NAME + Sulfaphenazole. Local heating to 42°C was performed and skin blood flow was measured with Laser Doppler flowmetry. All data are presented as % maximal cutaneous vascular conductance (CVC). All drug sites attenuated plateau CVC from the control site (85±2%) to 79±3% with sulfaphenazole, 71±3% with TEA, 39±3% with L‐NAME, 23±2% with L‐NAME + sulfaphenazole, and 13±2% with L‐NAME + TEA (not different from baseline). Furthermore, the initial peak was just 17±2% with L‐NAME + TEA. These data suggest EDHFs are responsible for the remaining 40% of the plateau phase, as administration of TEA in combination with L‐NAME abolished the majority of hyperemia. These data also suggest that EETs contribute to about half of the EDHF response.Supported by NIH Grant HL081671
The effect of voluntary hypocapnic hyperventilation on thermoregulatory responses in exercising humans
Authors: Fujii Naoto , Honda Yasushi , Komura Ken , Tsuji Bun , Sugihara Akira , Watanabe Kazuhito , Kondo Narihiko , Nishiyasu Takeshi 
Published: June 2021

We tested the hypothesis that voluntary hypocapnic hyperventilation (VHH) attenuates thermoregulatory responses in exercising humans. 10 healthy active males performed cycling exercise at 120W (30°C, 50%RH) during 1) spontaneous breathing, 2) eucapnic voluntary hyperventilation, and 3) VHH. Cutaneous vascular conductance was evaluated as cutaneous red blood cell flux measured by laser‐Doppler flowmeter/mean arterial blood pressure at forearm (CVCforearm) and forehead (CVCforehead). Forearm sweat rate was measured by ventilated capsule method. Our results indicated that esophageal temperature (Tes) threshold for increases in CVCforearm and CVCforehead was significantly or tended to be higher, while slope relating Tes with CVCforearm was significantly or tended to be lower in VHH than in the other two conditions. Neither Tes threshold nor slope for sweat rate was different among conditions. These results suggest that in exercising humans, although VHH does not affect sweat response, it attenuates cutaneous vasodilation response, and this attenuation is greater for forearm than forehead skin.This study was supported by grants from the Ministry of Education, Science, and Culture of Japan. N. Fujii is the recipient of a research fellowship for young scientists from Japan Society of the Promotion of Science.
Cold air breathing during isometric handgrip: effect of healthy aging on coronary blood flow
Authors: Muller Matthew David , Gao Zhaohui , Mast Jessica , Blaha Cheryl , Drew Rachel C , Leuenberger Urs A. , Sinoway Lawrence I. 
Published: June 2021

Cold air inhalation and isometric exertion both trigger symptoms of angina, but the underlying causes are unknown. The current echocardiography‐based study sought to determine the effect of healthy aging on coronary blood flow velocity during a combined handgrip and cold air inhalation protocol (COLD+GRIP). Fifteen young (25±1 years) and eleven older (63±1 years) healthy subjects underwent a 2‐minute bout of isometric handgrip (30% MVC) while inspiring cold air (−15°C) through a custom system. Transthoracic echocardiography was used to measure coronary blood flow velocity in the LAD artery. Finometer‐derived mean arterial pressure (MAP), heart rate (HR), air temperature, and grip workload were monitored continuously. Unpaired t‐tests were used to assess group differences. Height, weight, BMI, grip workload, and resting HR were not different between groups. The change in HR during COLD+GRIP was significantly blunted in the older subjects (Δ=7±2 bpm) compared to younger subjects (Δ=20±3 bpm) while the change in MAP was not different between groups (OLD Δ=23±3 vs. YOUNG Δ=24±2 mmHg). The change in coronary blood flow velocity was also not different between groups (OLD Δ=5.3±1.1 vs. YOUNG Δ=6.8±2.1 cm/sec). In conclusion, healthy aging blunts the HR response to COLD+GRIP, which may act to prevent ischemia.This study supported by Wilderness Medical Society Grant (MDM), P01 HL096570 (LIS) and UL1 RR033184 (LIS)
Mitochondria function and structure in brown adipose tissue is influenced by maternal low salt intake during the perinatal period
Authors: Lopes Karen Lucasechi , Dos Santos Elisabete Alcantara , Furukawa Luzia Naoko Shinohara , Heimann Joel Claudio 
Published: June 2021

ObjectiveTo evaluate brown adipose tissue (BAT) structure and function in female offspring of dams fed low salt diet during the perinatal period.MethodsFemale Wistar rats were fed low (LS: 0.15%) or normal (NS: 1.3% NaCl) salt diet since 8 weeks of age. At 12 weeks of age they were mated. After weaning, all offspring, were fed standard chow. Body temperature (T) was measured during 24 hours in adult female offspring (oLS or oNS) exposed to a cold (C) or room temperature (RT) environment. Gene expression (GE) of uncoupling protein‐1 (UCP1). PPARγ (PP), PGC1α (PG) and FOX C2 (FO) and mitochondria surface area (MIT) by electron microscopy were analyzed in BAT. Serum coenzyme Q10 was measured by HPLC.Results(p<0.05, n=5/group): Compared to RT, during day time, T was lower in both offspring groups exposed to C. During night time, T was lower only in oNS exposed to C. Compared to oNS, GE of UCP1, PP and FO were lower (20%, 19%, and 57%, respectively) in oLS exposed to RT but not to C. GE of UCP1 and PG were higher (24% and 43%, respectively) in oLS exposed to C than in oLS exposed to RT. MIT was higher (76%) in oNS exposed to C than oNS exposed to RT. Compared to RT, Q10 was higher (110%) in oNS and lower (53%) in oLS exposed to C.ConclusionsLow salt intake during the perinatal period is associated with alterations in the response to cold exposure and of gene expression of factors related to energy metabolism in the offspring.Supported by FAPESP.
Local skin temperature alters cutaneous vasoconstrictor responses to a simulated hemorrhagic challenge while heat stressed
Authors: Pearson James , AI Lucas Rebekah , Crandall Craig G 
Published: June 2021

Tolerance to simulated hemorrhage is reduced with hyperthermia, due in part to inadequate cutaneous vasoconstriction. It is unclear how elevated skin temperatures, as experienced by soldiers on active duty, influence cutaneous vasoconstriction during simulated hemorrhage. 8 healthy males (34 ± 9 yr, 80.2 ± 4.2 kg) underwent a simulated hemorrhagic challenge via lower body negative pressure (LBNP) to pre‐syncope while heat stressed sufficient to increase core (Tcore Δ1.2 ± 0.2°C) and mean skin temperatures (Tsk mean 38.2 ± 0.7°C). Local skin temperatures at three forearm sites were held at 35.2±0.6°C, 38.2±0.2°C and 41.3± 0.7°C throughout heat stress and LBNP. At pre‐syncope mean arterial pressure declined (74±6 to 53 ± 8 mmHg P < 0.0001) while mean Tsk (38.2±0.7°C; P = 0.92) and local Tsk (35.1±0.8; 38.3±0.3 and 41.5±0.6°C; P > 0.05) were unchanged relative to heat stress baseline (i.e., pre‐LBNP). The magnitude of reduction in cutaneous vascular conductance during the final 90 seconds of LBNP from heat stress baseline was influenced by local Tsk (8% at ~35°C; 3% at ~38°C and 2% at ~42°C; P < 0.0001). In hyperthermic individuals the extent of cutaneous vasoconstriction during a simulated hemorrhage is dependent on skin temperature. In situations where a soldier's skin temperature exceeds 38°C, cutaneous vasoconstriction to a hemorrhagic challenge is likely negligible.NIH HL61388 and HL84072
Tolerance to a hemorrhagic challenge during heat stress is improved with inspiratory resistance breathing
Authors: Brothers R. Matthew , Ganio Matthew S. , Lucas Rebekah A. I. , Crandall Craig G 
Published: June 2021

The mechanism(s) by which heat stress alters blood pressure control and tolerance to a simulated hemorrhagic challenge is multifaceted; however, heat‐induced reductions in central blood volume play a key role. Inspiratory resistance breathing improves blood pressure control and tolerance during simulated hemorrhage in normothermic individuals. It is unknown if similar improvements occur with this maneuver in heat stress conditions. This study tested the hypothesis that inspiratory resistance breathing improves tolerance to simulated hemorrhage in individuals with elevated internal temperatures. On 2 separate days, 8 subjects performed a simulated hemorrhage challenge (lower body negative pressure, LBNP) to pre‐syncope following an increase in internal temperature of 1.5 °C. During one trial subjects breathed through an inspiratory impedance device set at 0 cmH20 of resistance (Sham) while on the other day the device was set at −7 cmH20 of resistance (Experimental). Tolerance was quantified as cumulative stress index (CSI). Subjects were more tolerant to the LBNP challenge during the Experimental protocol as indexed by a larger CSI (Sham: 520±306 mmHg × min; Experimental: 682±324 mmHg × min, P<0.01). These data indicate that inspiratory resistance breathing modestly improves tolerance to a simulated hemorrhagic challenge during heat stress.Support NIH‐HL61388 & HL84072
Simulation of expired nitrogen (N2) after inhaling argon (Ar) at 1 atmosphere
Authors: Cruz Julio Cesar 
Published: June 2021

Expired Ar and N2, after inhaling Ar, were obtained in 1965 and published in 1991 (Cruz. Respir. Physiol. 86:1,1991). However, only Ar data was used to develop a model of inhaled inert gases. Because expired N2 behaved differently than Ar, especially, after holding the breath at 10s and 20s, at the end of inspiration, N2 was ignored. After introducing a new equation where FAr is a function of lung volume and time (unpublished), I was able to understand how Ar was inhaled and distributed in the alveoli. I learned that the expired Ar was generated by uneven flows from parallel regions of the lung. Now, I'm presenting the simulated expirogram of N2 (Figure, heavy line) after inhaling in 2s, 1.9L of 21% O2, 79% Ar from FRC (4L) and exhaling in 3s to RV (1.4L). New concepts were introduced in mixing the inhaled gas with the expiratory reserve volume (ERV), by the mechanism of convection‐diffusion during inspiration (Caucha et al. Am. J. Respir. Crit. Care Med. 183: A5180, 2011). These concepts are here applied. At FRC, the amount of alveolar N2 (3.245L) was distributed from apex‐to‐base of the lung following West lung model. The amount of N2 in the ERV was 2.114L, which was mixed with the amount of Ar that reached the alveoli (1.165L). The simulated expired N2 (thin line) was insufficient to reach experimental N2 (symbols) because of the assumptions of the expired Ar used: VD=425ml and k value (50L−1) of the exponential equation, the latter produced a progressive decline of Ar from VD to ERV. In order to fit the experimental N2 data, it was necessary to reduce the VD to 370ml and k to 40L−1. In addition, it was added 101ml of alveolar N2 present in the RV that diffused to ERV during Ar inhalation. It is concluded that the N2 expirogram is not the mirror image of the Ar expirogram.Supported in part by the Centro de Enseñanza, Investigación y Servicios (CEIS).
Hyperthermia potentiates the IL‐6 mRNA response to LPS in C2C12 muscle cells
Authors: Welc Steven S , Chen Dan L. , Clanton Thomas L. 
Published: June 2021

In heat stroke and bacterial infection, skeletal muscles (SM) can be exposed simultaneously to hyperthermia (HT) and endotoxin. Both are potent stimuli of IL‐6 in SM. We hypothesized that when these stimuli act together they potentiate SM IL‐6 production, which could implicate a role for SM in whole body innate immune responses.Aims1) to treat C2C12 cells with LPS or LPS+HT (42°C) and compare IL‐6 mRNA at 1, 2, 3, and 6 h, 2) to compare IL‐6 protein between treatments, and 3) to compare the response of myoblasts (MYOB) and myotubes (MYOT) to these co‐stimuli. Cells were supplemented with LPS (1 ug/ml) and simultaneously exposed to 37°C or 42°C for 1 h, then harvested or allowed to recover at 37°C for 1, 2, or 5 h. In a separate experiment, MYOT were treated with LPS (1000, 100, 10, and 1 ng/ml) and the supernatant was sampled at 6 h and analyzed for IL‐6 protein. Significant up regulation of IL‐6 mRNA was seen in MYOB and MYOT in response to LPS (P<0.05). Furthermore, the addition of HT potentiated the increase of IL‐6 mRNA compared to LPS alone (P<0.05); the amplification spanned 3h (MYOB) and 6 h (MYOT). Interestingly, IL‐6 protein was either not different or attenuated in HT+LPS vs. LPS. Results further demonstrate that HT is a functional stimulus for IL‐6 mRNA, possibly part of the HSF‐initiated heat shock response. We speculate variations in IL‐6 protein are a consequence of translational inhibition associated with mild heat shock.Supported by: AHA #11GRNT7990119
Hypothalamic mechanisms relating to improvement of thermal tolerance in heat‐and‐exercise‐acclimated mice
Authors: Tokizawa Ken , Lin Chen-Hsien , Uchida Yuki , Sakakibara Shin-ichi , Nagashima Kei 
Published: June 2021

Repeated exposure to moderate heat improves heat tolerance and acclimation. Exercise induces the improvement more effectively than just being at rest. The underlying central mechanisms of those phenomena have remained unclear.Male mice were individually housed at 32°C (HE) or 25°C (NE). The mice in two groups had two‐different exercise conditions: with (EXE) and without (CON) access to running wheels. After eight weeks, the mice had a 2‐h exposure at 36°C.Core temperature and oxygen consumption were lower in HE groups than in NE groups. In the heat exposure of 36°C, core temperature was lower in EXE groups than in CON groups during the first 1 h of the exposure. Ki67‐immunoreactive cell, a marker of cell proliferation, was not observed in the hypothalamus in NE‐CON mice. However, the cells were found in medial preoptic nucleus and dorsomedial hypothalamus in NE‐EXE, HE‐CON, and HE‐EXE mice. cFos immunoreactive cell in the median and medial preoptic nucleus was greater in EXE groups than in CON groups.These results may indicate that daily exercise and long‐term exposure to mild heat, separately, are sufficient to improve heat tolerance and acclimation respectively, and their combined effect induces both improvements. Neurogenesis and neuronal reactivity in the hypothalamus may be responsible for these thermal adaptations.
Modeling Intracranial Pressure in Microgravity during Parabolic Flight
Authors: Bachman Larry Lee , Patterson Kevin G. , Hegstad Thomas M. , Grigoryan Edward A. , Sayad-Shah Mehria , Hargens Alan R. 
Published: June 2021

Some astronauts return from spaceflight with papilledema probably due to intracranial hypertension secondary to head‐ward fluid shifts.Study objectives were to determine (1) the feasibility of venous congestion as a mechanism contributing to elevated intracranial pressure (ICP), and (2) the angle of head‐down tilt (HDT) that best represents ICP measured in microgravity.Our student team constructed a physical model of neck and cranial circulations in accordance with average adult human proportions to produce pressures and flows equivalent to physiological norms while upright, supine and at various tilt angles. The model flew aboard two NASA parabolic flights in July 2011.Jugular venous pressure and ICP changed in parallel and linearly during partial gravities, but rose disproportionately in microgravity to the same magnitude regardless of arterial pressure, central venous pressure or flow rate, corresponding to values measured at 11±5º HDT. Venous flow resistance increased 300% in microgravity, possibly due to unique flow properties through collapsible vessels. Results suggest that venous pressures elevate ICP, and future crewmember studies should examine cervical venous pressures, flows and valve incompetence. Moreover, countermeasures should focus on lowering cranial venous pressures by facilitating cephalic venous return.Supported by NASA RGSFOP, CA Space Grant, and UCSD Dept of Ortho. Surg.
Pan‐omic Approaches to Study the Effects of Microgravity on Host Responses to Toxins
Authors: Waddy Edward , Chakraborty Nabarun , Gautam Aarti , Santos William , Hoke Allison , Jett Marti , Hammamieh Rasha 
Published: June 2021

Microgravity, as indicated by previous studies, enhances bacterial virulence but depresses a host's immunity cascade. Presumably, pathogenic insults occurring in space may trigger altered immunological pathways in host cells. Understanding this paradigm is essential to establishing proper wound care management. A host toxin model was designed to address this research hypothesis and was executed aboard the Space Transportation System (STS)‐135. Preparatory ground work focused on designing a bioreactor‐based experimental model that could be integrated with the Cell Culture Module (CCM); which is semi‐automated equipment that was previously operated in space.Human microvascular endothelial cells were inoculated in 6 bioreactors on the ground, and the CCM supported these cells for the first 10 d of flight. Four bioreactors batched in 2 were exposed to lipopolysaccharide (LPS), an endotoxin commonly found in gram‐negative bacteria, for two different time periods (4 h and 8 h). At the end of each time point the cells were fixed and maintained in a fixed state until after the STS‐135 landed.Molecular samples extracted from the retrieved cells were found to have good integrity. A high throughput pan‐omics study, followed by in silico data analysis, is underway to identify the genomic signatures and pathways, and disease footprints corresponding to microgravity induced immunity cascades.
Angiopoietins regulate capillary network in non‐obese type 2 diabetic muscle, but VEGF is not necessary for the angiogenic response to exercise
Authors: Fujino Hidemi , Kondo Hiroyo , Murakami Shinichiro , Fujita Naoto , Nagatomo Fumiko , Ishihara Akihiko 
Published: June 2021

PURPOSETo gain insight into the regulation of angiogenic process, we visualized the capillary network and evaluated the angiogenic and metabolic factors over the course of exercise training in non‐obese type 2 diabetes.METHODSThe Goto‐Kakizaki (GK) rats were randomly divided into an exercise training (T2DM+Ex) and a sedentary (T2DM), while the Wistar rats were used as a control (Con). T2DM+Ex rats were trained at a low‐intensity for 60 min on a treadmill 6 times a week for 3 weeks. The 3‐D capillary network in soleus muscle was visualized using confocal laser microscopy. The expression of angiogenic factors (VEGF, KDR, Flt‐1, Ang‐1, Ang‐2, and Tie‐2), HIF‐1 alpha, AMPK and GLUT4 in the soleus muscle were determined by TaqMan probe‐based real‐time PCR.RESULTSThe capillary volume of the soleus muscle was lower in T2DM than in Con rats, whereas that in T2DM+Ex was higher. Angiopoietin pathway and metabolic factors in the T2DM+Ex were significantly increased compared with those in Con and T2DM although VEGF was not changes among three groups.CONCLUSIONThese findings suggest that exercise training improves the regression of capillary network in diabetic muscle without the change of VEGF, and that the angiopoietin pathway in diabetic muscle could be upregulated by exercise training. Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Fast‐To‐Slow: Myosin Heavy Chain Alterations in Response to Altered Six1 Gene Expression
Authors: Collins Brittany C , Gordon Bradley S , Kostek Matthew C 
Published: June 2021

Muscle activation patterns (e.g. exercise) affect muscle fiber‐type proportions in skeletal muscle. The developmental gene, Six1's, expression is altered by exercise, and altering its expression affects fiber‐type proportions in mice, though how is unclear.PURPOSEExamine the effect of Six1 expression on the myosin heavy chain (MyHC) genes during muscle fiber formation.METHODSC2C12 mouse myoblasts were grown in standard conditions. When cells reached 80% confluence, they were transfected with Six1 over‐expression vectors or empty vector control. 24 hours later, cells were switched to differentiation medium. After four days, cells were harvested. Six1, MyHC, and Myogenin gene expression was analyzed by qRT‐PCR.RESULTSWhen compared to empty vector control, Six1 expression increased 700 ± 243.4 fold (p = 0.02), MyHC‐IIb expression decreased 2 ± 0.12 fold (p = 0.01), MyHC‐IIx decreased 1.5 ± 0.09 fold (p = 0.05), MyHC‐I increased 2 ± 0.24 fold (p = 0.03), and MyHC‐IIa expression did not change. Six1 over‐expression caused a Myogenin increase 2.7 ± 0.34 fold (p = 0.02). A second Six1 expression vector confirmed these results.CONCLUSIONSix1 over‐expression differentially affects the muscle fiber‐type gene program during the formation of a muscle fiber. Together with our previous in‐vivo data, this suggests that Six1 expression affects the fiber‐type shift induced by muscle activation patterns.