bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravital Video Microscopy of Forelimb Capillary Blood Flow in Rat Skeletal Muscle
Authors: Fraser Graham 
Published: June 2021

ObjectiveThe present study describes the development of a novel in vivo microvascular preparation for the investigation of capillary blood flow in the extensor carpi radialis longus (ECRL) muscle of rat. Blood flow measurements in the forelimb provide an alternative to other contemporary vascular preparations and is particularly useful for investigating capillary blood flow in disease models where hind limb flow is impaired (e.g. hind limb unloading, reduced uterine perfusion pressure etc.).MethodsTwo male Sprague‐Dawley rats, 174 and 161g were anaesthetized with pentobarbital, tracheotomized, ventilated, and maintained in a normotensive state via minimal saline infusion in the jugular vein. The skin on the lateral side of the right forelimb was removed exposing the muscle capsule surrounding the extensor carpi radialis longus and brevis muscles. The distal tendon of the ECRL was secured with a silk ligature and the muscle was carefully isolated and reflected onto an inverted microscope stage. The muscle was bathed in warm saline and isolated from the air via polyvinylidene chloride film and a glass coverslip. Ten – twenty, 1 minute video sequences of capillary blood flow at 20X magnification were recorded in each animal. Videos were analyzed offline using custom software written in MATLAB yielding frame‐by‐frame measurements of capillary hemodynamics and oxygen saturation.ResultsCapillary measurements were made in a total of 69 vessels (31 ‐ 38 in each animal), with erythrocyte velocities of 196.8±40.2 μm/s; tube hematocrit 19.9±2.9 %; 10.7±0.7 cells/s; and entrance and exit oxygen saturation of 70.4±5.6 % and 55.8±4.6% respectively.ConclusionsWe demonstrate direct measurement of microvascular hemodynamics and capillary oxygen saturation in a novel intravital preparation using rat ECRL muscle.
Effect of Gastric Bypass Surgery on Endothelial function and Heart Rate Variability
Authors: Lee Kyuwan , DeVallance Evan , Grogg Kristen , Mason Rebecca , Hull Robert , Rosati Kristen , Tabone Lawrence , Frisbee Jefferson , Chantler Paul 
Published: June 2021

The obesity epidemic in the US has reached 155 million people. Obesity is associated with increased incidence of cardiovascular (CV) and metabolic diseases. The use of gastric bypass surgery has been shown to decrease excess body weight and reduce CV risk. Although, more than 100,000 procedures were performed during the past decade, it is unclear how it contributes to endothelial and autonomic function. The purpose of this study was to examine the outcomes of gastric bypass surgery on endothelial function and heart rate variability (HRV).We assessed 12 gastric bypass patient's peripheral arterial and endothelial function along with HRV using EndoPAT device, pre and 1 week post‐surgery.The mean of augmentation index (AI) was lower (p<0.05) 1 week post‐surgery (1.7±8.0 to ‐7.2±4.1) with an increase in mean of AI pulse (178±12 to 193±46, p<0.05). LF/HF ratio was increased (1.03±0.26 to 1.34±0.28, p<0.05) after gastric bypass surgery suggesting that it may contribute to improved autonomic modulation of CV function. In contrast, no changes were found in endothelial function. These findings show that gastric bypass surgery improves the parasympathetic to sympathetic input on the heart and peripheral arterial stiffness despite no change in endothelial function.
Aging and Atherosclerosis Impair Hematopoietic Stem Cell Function
Authors: Porto Marcella , Rodrigues Bianca , Bezerra Geisiane , Campagnaro Bianca , Menezes Thiago , Pereira Thiago , Vasquez Elisardo , Meyrelles Silvana 
Published: June 2021

BackgroundStem cell function is compromised with aging, especially when a cardiovascular disease is associated. The aim of this study was to evaluate how aging and atherosclerosis affect bone marrow hematopoietic stem cell (HSC) function in mice.Methods: Male mice were divided into C57 and apoE‐/‐ (2, 12 and 24‐month‐old) groups. Oxidative stress was assessed by 2,7‐dichlorofluorescein (DCF) by flow cytometer. For apoptosis detection, HSC were incubated with Annexin V‐FITC and propidium iodide (PI). Plasma inflammation markers, IL‐6 and MCP‐1, were measured. Also, senescence was evaluated by acridine orange protocol. Lipid profile and aortic lipid deposition were also analyzed. Data are mean±SEM. Statistical analysis was performed with two way ANOVA test and Tukey pos hoc.Results: Aging and atherosclerosis increased ROS levels and apoptosis in HSC. Senescence was also increased with aging and atherosclerosis, especially in 24‐month‐old mice. Atherosclerotic adult and aged animals showed higher levels of IL‐6 and MCP‐1. As expected, atherosclerosis augmented total serum cholesterol levels and aortic lipid deposition.ConclusionThe present study provides evidence that aging and atherosclerosis can cause oxidant stress and impair HSC function. Such findings could lead to new insights into the mechanisms by which aging and atherosclerosis can affect immunity and inflammation.
Progressive mechanisms on naïve wound healing process in an animal model with skin injury
Authors: Choi Jeonghyun , Hong Yunkyung , Hong Yonggeun 
Published: June 2021

Cutaneous wound healing is a complex and coordinated series of events. A wide variety of growth factor and cytokines are involved in the regulation of all phased of wound healing. Inflammatory phase of the healing process develops during 24 hours from the moment when an injury occurred and last for up to 48 hours or above that. The early inflammatory phage of wound healing cascade is characterized by subsiding of the vessel contraction followed by widening their lumen, which promotes leaking of plasma to the wound site. The changes are supported by reactive oxygen species (ROS). Low levels of ROS are important in wound repair by protecting the injured area against microbes along with enhancing angiogenesis. Normal ROS levels promote the collagenase activity MMPs and other signalings which help wound reepithelilization through maintaining normal keratinocyte migration and proliferation. Normal ROS also aid in the production of collagenI,III and their subsequent cross linking. High levels of ROS increase apoptosis of keratinocytes and damages fibroblasts, causing them to become senescent and lose the ability to produce extracellular matrix. ROS stimulate apoptosis through the C‐junN‐terminal kinase (JNK) pathway and stimulates translocation of JNK to the mitochondria. The aim of this study was that to provide inflammatory phage of normal wound healing process without intervention.Funding: 2012R1A1A2005089, 2013R1A2A2A01067169, KGM4611512
Screening for early detection of stomach cancer in Kazakhstan: first results
Authors: Orazova Galiya , Karp Leonid , Dossakhanov A. 
Published: June 2021

IntroductionOver the last 15 years (1999‐2013) more than 42 thousand patients have been registered with stomach cancer (SC) identified for the first time.Materials and methodsIn 2013, screening was introduced in Kazakhstan with the aim of early detection of stomach and esophageal cancers. The target population is persons aged 50‐60 years. Screening by endoscopic examination was conducted in a pilot mode in 4 regions and in Astana and Almaty cities.Results150,546 persons were examined in the targeted age groups.1,649 patients were identified with disorder of gastro‐intestinal tract mucosa (0.9% from examined patients), of whom 1,589 people (96.4%) were registered for medical checkup. Statistically significant differences of endoscopic esophageal and stomach disorders frequency were identified between max (2.8%) and min (0.4%) parameters (p<0.05). The frequency of the disorder was the highest in the age group of 60 years. According to the data of primary medical care the diagnosis of SC was achieved in 87 cases (0.05%). According to the endoscopic examination 79 cases of SC were identified (including 39 morphologically verified). According to the cancer registry, SC detectability is 0.04% from the number of examined patients. Complete agreement between primary medical care and cancer‐register data was observed only in one region. SC is identified more frequently at stage II (47.0%).ConclusionsAccording to the primary medical care and cancer registry data, there is mismatch in the results: almost in all regions both cases of stomach cancer over diagnosis in some regions and misreporting in others.
Hypometabolism in Endotoxic Shock Reflects a Thermoregulatory Response and Occurs Independently of Circulatory Hypoxia
Authors: Steiner Alexandre , Corrigan Joshua , Fonseca Monique , Flatow Elizabeth , Lewis Kevin , Brito Camila 
Published: June 2021

Oxygen utilization (VO2) is thought to fall in the late stages of septic shock because of mitochondrial dysfunction, circulatory hypoxia or both. However, the applicability of this conceptual framework to early septic shock is unclear. We investigated this matter in a rat model of lipopolysaccharide (LPS)‐induced shock (endotoxic shock). A novel experimental preparation was devised to simultaneously monitor oxygen delivery (DO2) and VO2 in rats whose thermoregulation had not been disrupted by anesthetics. Using a β3‐adrenergic agonist known to activate brown adipocytes, we found no evidence of metabolic impairment between 20 and 150 min post‐LPS. In spite of that, VO2 fell early in the LPS‐challenged rats, and such a fall in VO2 seemed to be driving a decrease in body temperature. The fall in VO2 was not preceded by any fall in cardiac output or DO2. Furthermore, no imbalance between VO2 and DO2 were encountered, and an analysis of NAD+/NADH ratios provided no indication of tissue hypoxia. Only when hypometabolism and hypothermia were prevented by exposure to a warm environment did an imbalance in the DO2/VO2 ratio become evident, and such an imbalance was associated with tissue hypoxia (reduction in NAD+/NADH ratio). It is concluded that reduced VO2 in early endotoxic shock (i) results from neither metabolic failure nor circulatory hypoxia, (ii) reflects a thermoregulatory adjustment, and (iii) serves as preemptive strategy to avoid hypoxia. Clinical data and conduct should be reexamined in light of these new findings.FundingFAPESP, AHA & CNPq.
Fluorescent Microspheres Injected into Skeletal Muscle to Observe Fluid Movement in Interstitial Space
Authors: Evertz Loribeth , Greising Sarah , Morrow Duane , Sieck Gary , Kaufman Kenton 
Published: June 2021

The force within a muscle may be assessed using intramuscular pressure measurements (IMP). However, a limiting factor in implementing this technology in the clinic is the observed variability of IMP measurements. The variability may be due in part to the flow of interstitial fluid. The objective of this study was to develop a technique for tracking interstitial fluid flow during muscle lengthening using fluorescent microspheres. Additionally, the effect of microsphere diameter on dispersion was evaluated. Fluorescent microspheres were injected into the rat tibialis anterior (TA) either before (right limb) or after (left limb) lengthening to 10% strain (n = 5). To help discriminate the effects of microsphere size, 10 µl of microspheres (0.25% by volume) were injected simultaneously: 0.1 µm in sky blue and 0.2 µm in yellow green. Once frozen, 20 µm muscle cross‐sections were stained and imaged using confocal microscopy to evaluate the microsphere's axial dispersion as a percent of muscle length. The microsphere dispersion was normalized to the muscle length. The fluorescent microspheres flowed with the interstitial fluid and did not penetrate the muscle fiber. There was significantly greater microsphere dispersion with passive strain (p‐value > 0.01) for lengthened samples (31±7%) compared to static samples (17±9%). Dispersion did not differ for the two bead sizes. In conclusion, this illustrates the microspheres track the interstitial fluid and passive lengthening results in additional dispersion.Supported by NIH under award number R01HD31476 and T32HL105355.
Estradiol enhances neutrophil infiltration into traumatically‐injured skeletal muscle
Authors: Le Gengyun , Jergenson Matthew , Lowe Dawn , Warren Gordon 
Published: June 2021

PurposeTo probe how estradiol modulates neutrophil infiltration and function following traumatic muscle injury.MethodsAdult, female C57BL/6 mice were ovariectomized and randomly assigned to no treatment or implantation of a 17‐b estradiol slow‐release pellet. Four weeks later, freeze injury was induced to tibialis anterior (TA) muscles and mice were allowed to recover for 1, 2, 3, or 4 days before sacrifice, blood collection, and TA muscle excision. Myeloperoxidase (MPO) activity, an indicator of neutrophil function, was examined in the muscles. H&E staining of TA cross‐sections were used to address neutrophil localization and FACS analysis was performed to quantify neutrophil infiltration. Neutrophils in the blood were counted by automated hematological analysis.ResultsMPO activity was 25‐125% greater in the injured muscles of estradiol‐treated mice (P<0.0001). Infiltration of neutrophils appeared in the first 24 hours and peaked at 3‐days post‐injury in muscles of mice with and without estradiol. FACS analysis revealed that compared to injured muscles from untreated mice, infiltrated neutrophils were 6‐61% greater in injured muscles from estradiol‐treated mice, with the peak difference at day 4 (24±6 vs 15±3 % of hematopoietic cells). The concentration of neutrophils in blood of estradiol‐treated mice was 40‐60% lower than that in untreated mice at 1, 2, and 3‐days post‐injury (P<0.001).ConclusionEstradiol increases neutrophil infiltration into muscle following traumatic injury. Supported by NIH grant R01‐AG031743.
Astaxanthin Supplementation Improves Decreased Mitochondrial Enzyme Activity and Capillary Regression during Recovery from Muscle Atrophy
Authors: Maezawa Toshiyuki , Kanazashi Miho , Tanaka Masayuki , Maeshige Noriaki , Kondo Hiroyo , Fujino Hidemi 
Published: June 2021

Reactive oxygen species (ROS) impairs mitochondrial respiratory chain and capillary structure in atrophied muscle. Impaired mitochondria and capillary are also associated with a decrease of exercise tolerance. Reloading promotes recovery from atrophy, whereas reloading induces the overexpression of ROS. Therefore, we investigated the effects of reloading and anti‐oxidant supplementation for the mitochondria enzyme activity, capillary number and oxidative stress marker during recovery from disuse‐induced muscle atrophy. Hindlimb unloading resulted in a reduction of citrate synthase (CS) activity, capillary‐to‐fiber (C/F) ratio and expression of PGC‐1α protein, and an increase of superoxide dismutase (SOD)‐2. Reloading after unloading improved the decreased CS activity and PGC‐1α expression level, but C/F ratio could not be recovered. Astaxanthin, anti‐oxidant, supplementation maintained all of them to control level through the unloading and reloading conditions. In addition, astaxanthin supplementation attenuated the overexpression of SOD‐2. These results suggest that astaxanthin supplementation approach may be effective as a therapeutic strategy under recovery conditions involving muscular debilitation.Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry Education, Culture, Sports, Science and Technology, and the internal funds of Fuji Chemical Industry Co. Ltd.
Rapid Onset Pressor Response to Static Handgrip in Young Normotensive Women with a Family History of Hypertension
Authors: Matthews Evan , Greaney Jody , Wenner Megan 
Published: June 2021

Older hypertensive adults display exaggerated blood pressure (BP) and muscle sympathetic nerve activity (MSNA) responses at the onset of static muscle contraction. Young normotensive adults with a family history of hypertension (+FH) are at a greater risk for developing future hypertension. We tested the hypothesis that young women with a +FH wouldhave exaggerated increases in BP and MSNA at the onset of static muscle contraction compared to those without a family history of hypertension (‐FH). We retrospectively examined beat‐by‐beat BP, heart rate (HR), and MSNA during the initial 30 seconds of isometric handgrip exercise at 30% of maximum voluntary contraction in 14 +FH (22±1 yrs, 21±1 kg·m‐2) and 14 –FH (22±1 yrs, 22±1 kg·m‐2) women. Resting mean arterial pressure (MAP;+FH 80±2 vs. –FH 79±3 mmHg), HR (+FH 62±3 vs. –FH 66±2 bpm), and MSNA (+FH 7±1 vs. –FH 10±2 bursts·min‐1) were similar between groups (all P>0.05). At exercise onset, the increases in MAP (+FH Δ11±2 vs. –FH Δ4±1 mmHg, P<0.05) was greater in +FH compared to –FH women. The increase in HR was also greater in +FH (+FH Δ 13±2 vs. –FH Δ 4±1 bpm P<0.05). The MSNA responses were not different between groups (+FH Δ3±1 vs. –FH Δ22±1 bursts·30s‐1, P=0.29). These data demonstrate that there is an exaggerated pressor response at the onset of static muscle contraction in young normotensive women with a +FH and further suggest that this may be due to greater increases in HR at exercise onset.Research supported by NIH Grant U54‐GM104941 (PI: Binder‐Macleod)
Identification of Pin1 Isomerase on Neuronal Cell Rescue in Ischemic Brain Injury
Authors: Lee Seunghoon , Won Jinyoung , Hong Yonggeun 
Published: June 2021

Pin1 contains two functional domains, an N‐terminal WW domain and a C‐terminal PPIase domain. The WW domain is a phosphorylation specific protein interaction module that directs Pin1 to its substrate‐proteins phosphorylated at certain serine or threonine residues followed by proline. Upon this binding, the PPIase domain catalyzes conformational change of the Pin1 substrates by isomerizing specific pSer/Thr‐Pro bonds; thus, we hypothesized that Pin1 can regulate neuronal cell death and neurogenesis through Pin1 inhibitor treatment after MCAo. To test the hypothesis, we elucidated roles of Pin1 following treatment of the Pin1 inhibitor at the sub‐acute phase after MCAo in rats. Juglone (1 mg/kg) was administered once a day for 7 days after MCAo. Histological and molecular analyses were used to determine apoptosis and neurodegeneration. MCAo+Jug leds to significant downregulation of Bcl‐2 and Bax the protein level compared with MCAo+veh (**p<.01). Ischemic brain injury promoted phosphorylation of Thr231 motif on tau as shown in Western blot. MCAo+Jug was shown to reduce the levels of Pin1 and tau5 in both Western blot and immunostaining (**p<.01). These results suggest that Pin1 isomerase acts as a pro‐apoptotic molecule in ischemic‐induced neuronal cell death after MCAo. Additionally, we suggest that Pin1 inhibition might alleviate the acceleration of apoptotic cell death from acute to sub‐acute after MCAo in rats.Funding: 2012R1A1A2005089, 2013R1A2A2A01067169, KGM4611512
Improvement of nephrotic syndrome by Banggihwanggitang.
Authors: Lee So min , Chung Sun‐Ku , Lee Seo‐young , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Nephrotic syndrome is associated with altered renal handling of sodium along with changes of renal epithelial Na channel (ENaC), leading to the development of edema and ascites.The dried sclerotia of Banggihwanggitang (BHT) has been used for the treatment of chronic kidney disease. This study was conducted to evaluate the effects of BHT on puromycin aminonucleoside (PAN)‐induced renal functional derangement and the change of ENaC expression. The nephrotic syndrome animal models were constructed by PAN 75 mg/kg injection and then were treated with losartan (30 mg/kg/day) or BHT (200 mg/kg/day) for 7 days. Consequently, BHT group was significantly improved the proteinuria and ascites. In addition, the plasma level of triglyceride, total cholesterol, and low density lipoprotein (LDL)‐cholesterol were significantly decreased in BHT. Besides, BHT group attenuated the PAN‐induced increase in ENaC protein expression. BHT was significantly suppressed PAN‐induced organic osmolytes regulator such as serum‐ and glucocorticoid‐inducible protein kinase (Sgk1), and mineralocorticoid receptor (MR) mRNA expression.Taken together, BHT improve nephrotic syndrome including proteinuria and ascites, through inhibition of ENaC. Thus, Banggihwanggitang is involved in the body‐fluid regulation via inhibition of water and sodium channels against renal disorder such as edema or nephrosis.
Anti‐Fibrotic Effect of Ajulemic Acid in Bleomycin‐Induced Lung Fibrosis
Authors: Lucattelli Monica , Fineschi Silvia , Selvi Enrico , Garcia Gonzales Estrella , Balistrieri Epifania , Lorenzini Sauro , Galeazzi Mauro , Distler Jorg , Lungarella Giuseppe 
Published: June 2021

Ajulemic acid (AjA) a synthetic analogue of tetrahydrocannabinol can prevent progression of skin fibrosis in experimental systemic sclerosis. We aimed to investigate if AjA modulate lung fibrogenesis induced in mice by bleomycin (BLM).The efficacy of AjA was evaluated in inflammatory (within 7 days after BLM) or in early fibrogenic phase (from 7 days onward). DBA/2 mice were i.tr. instilled with a single dose of BLM (0.1 μg/50μl saline) and AjA given orally, once a day,starting at day 1 (Groups 3, 4) or day 8 from BLM (Groups 5, 6). AjA in safflower oil was given at a dose of 1mg/kg (Groups 3, 5) and 5mg/kg (Groups 4,6). Group 1 and Group 2 received safflower oil or BLM, respectively. Mice were sacrificed at day 14 and 21 after BLM and lungs were processed for histology and morphometry, examined for HO‐proline and expression of TGF‐β, CTGF, α‐SMA, and PPAR‐ γ.BLM induces lung fibrosis with significant increase of HO‐proline (Group 1: 174.32 ± 30 μg/lung; Group 2: 280± 35 μg/lung; p<0.01). AjA treatment decreases significantly the fibrotic response as revealed by morphometry and HO‐proline content (Group 3: 172±29; Group 4: 209± 38; Group 5: 189±32; Group 6: 186±20). Marked decrease of TGF‐β and CTGF expression, significant reduction of α‐SMA positive cells and significant increase of PPAR‐γ expression is observed in AjA groups.AjA exerts potent anti‐fibrotic effects in BLM‐lung fibrosis also when given during the fibrogenic phase. The reduced ECM deposition is associated with decreased expression of the profibrotic cytokines TGF‐β and CTGF and increase of PPAR‐γ positive cells.
Eye Can Learn About Physiology through PhUn Week
Authors: Alarcon Fortepiani Maria , Ibarra Jessica 
Published: June 2021

Physiology Understanding (PhUn) Week, a national science outreach program of the American Physiological Society provided a great opportunity to deliver innovations in teaching into the classroom in San Antonio. The city has a high prevalence of vision problems, some of them which may be preventable with proper nutrition. Most PhUn Week activities engage students on the physiology of the heart, circulation, and the lungs, but we decided to introduce and enhance middle school student's understanding of the eye during PhUn Week. We developed a collection of hands‐on vision physiology activities specifically for middle school students.MethodIn 2014, over 500 middle school students from Clara Driscoll and E.T. Wrenn Middle Schools in San Antonio, Texas participated in several 10 minute activities that we developed during PhUn Week. The activities included examining the parts of the eye looking up close at cow eye specimens and a human eye anatomical model to make functional correlates for each structure examined. We further evaluated the integrity of this functional system by demonstration of pupils responding to light, finding their blind spot, showing them x‐ray vision, and shifting images. During the 45 minute session the students were also given a presentation describing the eye safety, common diseases of the eye, and contained a discussion on eye nutrition.ResultMany students gained a greater understanding of the eye, how it works, its importance, and the link between good nutrition and healthy eyesight. These activities also highlighted for students the impact of physiology in their daily lives – to sense the world around them.ConclusionBecause of PhUn week, we were able to deliver innovative vision physiology activities at middle school in our community.