bluuebunny/crossref_metadata_2025_split huggingface dataset:
The muscle carnosine and taurine content of elderly non‐obese korean males with impaired glucose tolerance
Authors: Harris Roger C , Kim Hyo J , Jones Glenys , Lee Jon S , Kim Chang K , Wise John A 
Published: June 2021

Carnosine (β‐Alanylhistidine) (Carn) occurs in high concentrations in muscle where it contributes to H+ buffering during exercise. Synthesis is limited by the availability of β‐Alanine synthesised in the liver from Uracil and transported to muscle fibres, but is enhanced by the inclusion of β‐Ala (or a β‐Ala source such as Carn) in the diet. Whilst the transport of β‐Ala into muscle is still not fully understood there is evidence that this may be linked to the action of insulin. Taurine (Tau), a beta‐sulfonic amino acid which shares the same transporter as β‐Ala, was also investigated in this study.PURPOSETo investigate if muscle Carn or Tau are altered in patients with impaired glucose tolerance (IGT).METHODA single muscle biopsy of the vastus lateralis was obtained from 8 elderly non‐obese Korean males (58–67 y) with IGT. ~2mg of freeze‐dried powdered muscle was analysed for Carn and Tau by HPLC. Results were compared to muscle values of 10 young (19–25 y) active Korean males determined at the same time by the same method.RESULTSThe mean muscle Carn and Tau contents of IGT subjects (21.5±3.8 and 44.9±12.0 mmol.kg−1 dm) were very similar to contents of younger subjects (22.1±2.8 and 42.8±10.3 mmol.kg−1 dm). Carn showed the same negative correlation to Tau in IGT as in younger subjects (a relationship previously observed in other subjects).CONCLUSIONMuscle Carn and Tau were unaffected by IGT or age in Korean non‐obese males.
Ca2+‐ and Sr2+‐activated contractile characteristics of permeabilized muscle fibers from dystrophic dogs
Authors: Lynch Gordon S , Murphy Kate T , Bizario Joao CS , Costa Maria CR , Pinto Mildre L , van der Poel Chris 
Published: June 2021

The Golden Retriever muscular dystrophy (GRMD) dog has a mutation in the dystrophin gene, suffers muscle wasting and weakness, and dies prematurely from cardiac or pulmonary failure. It is a relevant model for understanding the underlying mechanisms and investigating potential therapeutic approaches for Duchenne muscular dystrophy (DMD). Unfortunately, few GRMD colonies exist worldwide and there is a lack of information regarding aspects of muscle fiber function between dystrophic and healthy dogs. Our aim was to identify Ca2+‐ and Sr2+‐activated contractile characteristics of single permeabilized fibers from the biceps femoris muscles of 2‐year old GRMD dogs. Single fibers were attached to a force transducer, activated in Ca2+‐ and Sr2+‐buffered solutions to generate force‐pCa(pSr) relations, and then analyzed for myosin heavy chain and troponin‐C isoform composition. Specific force was ~25% lower in dystrophic dogs compared with litter mate controls (215 ± 18 kN/m2, n = 15 vs 160 ± 9 kN/m2, n = 15), but fiber sensitivity to Ca2+ was unchanged. A high proportion (~65%) of fibers from dystrophic dogs were ‘hybrid’ fibers as evident from their biphasic force‐pSr relations and combination of slow and fast troponin‐C isoforms. These functional assessments provide important information about the progression of muscular dystrophy in the GRMD model and its relevance to DMD.Supported by the Muscular Dystrophy Association (USA)
Eccentric contractions protect skeletal muscle from temperature‐induced contracture in Y522S RyR1 knock‐in mice
Authors: Ingalls Christopher Paul , Corona Benjamin T. , Rouviere Clement 
Published: June 2021

Mice with a malignant hyperthermia mutation (Y522S) of the ryanodine receptor (RyR1) can exhibit muscle contracture and die when exposed to elevated temperature. When stressed by elevated temperature (T), Ca2+ leak from the Y522S RyR1 and cellular accumulation is thought to produce reactive nitrogen species that modifies RyR1 resulting in sustained Ca2+ release and muscle contracture. Eccentric contractions are known to reduce muscle strength by impairing voltage‐gated Ca2+ release from RyR1. The purpose of this study was to determine if eccentric contraction‐induced injury would reduce contractures when EDL muscle from Y522S mice is incubated at 35°C. Anterior crural muscles from wild‐type (WT) and Y522S mice were injured by performing 150 eccentric contractions in vivo. EDL muscle function was assessed via force‐frequency (F‐F) experiments at 30 and 35°C 3 and 14 d post‐injury. At 30°C, uninjured EDL from Y522S mice exhibited stable resting force during the F‐F experiment, and peak force at 300 Hz (Po) was not different than WT mice. At 35°C, increases in resting force in Y522S mice at 3 (38%) and 14 (152%) d after injury were less than increases in uninjured muscle (322%). T‐induced decreases in Po in Y522S mice at 3 (34%) and 14 (36%) d were less than in uninjured muscle (65%). Eccentric contractions attenuate T‐induced contractures and reductions in active force in Y522S mice.Supported by NIH grant AR41802
Changes in junctophilin 1 contribute to strength deficits after eccentric contraction‐induced muscle injury
Authors: Corona Benjamin , Wilson Andrea K , Rouviere Clement , Hamilton Susan L , Ingalls Christopher P 
Published: June 2021

Performance of eccentric contractions (ECCs) disrupts excitation‐contraction (E‐C) coupling and induces strength deficits. E‐C uncoupling may result from disturbance to the SR / t‐tubule triad structure. Junctophilin 1 (JP1) is a triadic protein that is thought to be required for normal voltage‐gated SR Ca++ release. We hypothesize that ECCs alter tibialis anterior (TA) muscle JP1 protein content and that functional recovery from ECCs corresponds to recovery of JP1. To test the hypothesis we compared strength and JP1 changes after ECCs in wild type (WT; n =12) and malignant hyperthermia susceptible (Y522S; n =12) mice that recover function after ECCs faster than WT mice. The left anterior crural muscles (primarily TA muscle) of Y522S and WT mice performed 150 ECCs and a pre‐ and 3 or 14d post‐injury torque‐frequency test, in vivo. JP1: tubulin protein content was determined in injured and uninjured TA muscles. 3d post‐injury, torque and JP1 were reduced similarly in both WT and Y522S mice. 14d post‐injury, torque and JP1 were recovered in Y522S mice, but were still reduced in WT mice. Regression analysis indicated that reductions of JP1 are strongly associated with torque deficits (r = 0.70). These results indicate that JP1 is reduced following ECCs and suggest that recovery of JP1 contributes to the restoration of prolonged torque deficits in TA muscle.‐Supported by NIH grant R01 AR41802 (S.L. Hamilton)
Hypoxic Vasodilation in Human Skeletal Muscle: contributions of nitric oxide and vasodilating prostaglandins
Authors: Markwald Rachel R , Kirby Brett S , Carlson Rick E , Voyles Wyatt F , Dinenno Frank A 
Published: June 2021

We tested the hypothesis that nitric oxide (NO) and prostaglandins (PGs) contribute independently to hypoxic vasodilation, and that combined inhibition would reveal a potential compensatory interaction between these two dilators in the regulation of vascular tone. In 12 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to 5 minutes of steady‐state isocapnic hypoxia (O2 saturation ∼85%). All trials were performed during α‐ and β‐adrenergic blockade (via brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone. Hypoxic vasodilator responses were determined under control conditions, during independent NO synthase (NOS; L‐NAME) or cyclooxygenase inhibition (COX; ketorolac), and finally during combined NOS and COX inhibition. Drug order was counterbalanced across subjects. In both groups, acute hypoxia caused significant forearm vasodilation under control conditions (ΔFVC ∼25%; P<0.05), and this was not influenced by prior inhibition of NO or PGs. In contrast, combined inhibition of NO and PGs in both groups reduced hypoxic vasodilation by ∼90%. Our findings indicate that NO and PGs are not independently obligatory for regulating vascular tone during hypoxia, but that together they play a significant role in hypoxic vasodilation in human skeletal muscle.Supported by AG‐022337, HL‐087952
Hereditability Defect in Red‐Cell K in Hypertension
Authors: Delgado‐Almeida Antonio , Delgado Maria Carolina 
Published: June 2021

Background:Following our description of an hereditability of a decreased erythrocyte K [K]er independent of cell Na, in essential hypertension (EH), a long‐term study of RBC (Ki, Nai, H2O) content, plasma (Na, K, Cl, ionized Ca++), trans‐tubular K gradient (TTKG), total body K (TBK) and body water distribution by Bio‐Impedance Analysis was carried out in 185 hypertensives (47±19 y, 57 females; BP 167±11/101±7 mm Hg).Results:All cases had low Ki (85.3±6 mmol/l vs 96.2±4 mmol/l in normal, p<0.001) despite normal (82%) or mild elevated Nai (7.2±1.3 mmol/l vs 6.2±1.1 mmol/l in normal, p=NS), despite similar urinary Na excretion (107±22 vs 101±35 mmol/l). Patients with lowest Ki (78.3±5 mmol/l) had lower urinary K 21±15 mmol/l), TTKG (4.2±0.7) and higher 12‐h urinary volume (≥1.3 ml/min) than those with higher Ki (86.5±6mmol/l, p<0.002), urinary K (39±11mmol/l, p 0.004), TTKG (7.2±1.3) but lower 12‐h urinary volume (≤0.85 ml/min). Reversal of this abnormal Ki content in hypertensives was associated with decline and better control of BP (82%), fasting plasma glucose and regression of ST‐T alterations related to LVH hypertrophy (71%) or coronary artery disease (61%). Such body K disturbances, recorded at different month periods, unrelated to age, sex, race or dietary K intake in the hypertensives, and present in half (48%) of their normotensive offspring were implying a defective K mechanism in erythrocyte‐progenitor cells.Conclusion:These observations strongly suggest a critical role of RBC in normal body K homeostasis that is disturbed in EH.
Role of Renal NAD(P)H Oxidase in Dahl Salt‐Sensitive Hypertension
Authors: Manning R. Davis , Tian Niu , Moore Rebecca S , Pryor Janelle S , Stockstill Rachel 
Published: June 2021

The goal of this study was to determine the role of NAD(P)H oxidase in Dahl S hypertension. Rats were subjected to a 5‐week high or low Na diet with and without inhibition of NAD(P)H oxidase (apocynin [apo], 100mg/kg/d). The results after 5 weeks are shown below (values are mean ± SEM; † P<0.05 comparing Hi Na and Hi Na+apo groups; * P<0.05 compared to Low Na group). Compared to low Na intake, high Na intake caused marked increases in renal mRNA expression of NAD(P)H oxidase, arterial pressure, proteinuria and decreased renal hemodynamics. Apo treatment in Dahl S rats on high Na intake decreased renal NAD(P)H oxidase expression and arterial pressure, improved renal dysfunction, and attenuated renal injury. In conclusion, the renal NAD(P)H oxidase pathway may play an important role in causing renal oxidative stress and in the progressive increases in arterial pressure and renal damage and decreases in renal hemodynamics that occur in Dahl salt‐sensitive hypertension. Support NIH 51971.
Treatment
Hi Na
Hi Na+Apo
Low Na
Low Na+Apo

NADPH gp 91 mRNA (fold)
9.0±0.6† *
4.3± 0.8 *
1.0±0.2
1.7±0.3

NADPH p22 mRNA (fold)
5.8±1.8† *
2.1± 0.3
1.0±0.3
1.6±0.3

NADPH p47 mRNA (fold)
9.4±0.6† *
3.5± 0.6 *
1.0±0.2
1.5±0.2

NADPH p67 mRNA (fold)
7.8±1.2† *
2.9± 0.5
1.0 ± 0.2
1.2±0.2

Mean arterial pressure (mmHg)
183±3 † *
162± 4
103±2.4
102±1.5

GFR (ml/min)
1.9±0.1† *
2.8±0.1 *
3.3±0.25
3.3±0.1

Renal plasma flow (ml/min)
6.8± .5 † *
8.5± .3 *
11.6±.8
10.7± .5

Renal vascular resistance
53± 5 † *
36± 1 *
17±2
18±1

Proteinuria (mg/day)
174±12† *
137± 13
35± 6
37±7
Leptin icv blunts the renal sympatho‐inhibition of volume expansion (VE) in normal and fat fed Wistar rats
Authors: Johns Edward J. , Devoy Louise , Huang Chunlong 
Published: June 2021

This study investigated the impact of leptin icv on the renal sympatho‐inhibition arising from stimulation of the cardiopulmonary reflex in normal and high fat fed rats. Male Wistar rats, at 7 weeks of age, were fed either a normal (3.4% fat, n=6) or a fat diet (45% fat, n=4) for 4 weeks. The rats were anaesthetised and cannulae placed in the femoral artery and vein, electrodes sealed onto the left renal nerve and a cannula implanted into the right lateral cerebroventricle. VE, 30 min of saline iv at 0.25% of bwt/min, was performed before and 2 h after leptin was given icv at 5μg+10μg/h. Means ±SEM were subjected to ANOVA with significance at P<0.05. In normal Wistar rats, VE had no effect on blood pressure (BP), at 80±5mmHg, or heart rate (HR), at 384±23 bpm, but renal sympathetic nerve activity (RSNA), at 4.0±0.8 mV/s, fell by 51% (P<0.05). After 2h of leptin icv, VE decreased RSNA by 29% (P<0.05), which was less (P<0.05) than before leptin. In fat fed rats, BP was comparable to those on a normal diet but HR, at 433±9 bpm, and RSNA, at 11.4 mV/s, were significantly higher (both P<0.05), while VE reduced RSNA by 17.2% (P<0.05), which was smaller (P<0.05) than that in rats on a normal diet. Leptin icv did not change the response patterns of BP, HR and RSNA to VE.The data showed that leptin within brain appeared to exert a tonic inhibition on the cardiopulmonary mediated suppression of RSNA.
Renal Tissue Oxygenation with Renal Arterial Stenosis
Authors: Warner Lizette , Gomez Sabas , Haas John A , Bolterman Rodney , Bentley Michael D , Joyner Michael J , Lerman Lilach O , Romero Juan Carlos 
Published: June 2021

Functional renal oxygen consumption, VrO2 is due to tubular reabsorption of sodium (TNa) in the proximal (∼67%) and distal(∼30%) nephrons, resulting in compartments (cortex/medulla) with distinct VrO2/TNa relationships. A progressive drop in renal blood flow (RBF) with renal arterial stenosis (RAS), disrupts O2 delivery, vital for reabsorption. The overall objective for the study is to determine the intra‐renal regional alterations in tissue oxygenation (PtO2) and theVrO2/TNa relationship in acute RAS. The hypothesis is RAS is accompanied by intra‐renal regional changes in oxygenation. Unilateral acute RAS was induced in 8 pigs by an extra‐vascular balloon. RBF and PtO2 were measured continuously with an ultrasound flow probe during baseline, RBF autoregulation and 3 sequential decreases in RBF, recovery, and furosemide administration. VrO2 was determined using Fick arterio‐venous differences. There were concomitant decreases in VrO2, and PtO2 throughout the occlusion periods. Medullary PtO2 changes were 35% more pronounced than cortical. This study suggests medullary decreases in PtO2 are more aggravated than cortical changes with reductions in RBF, accentuating the medulla's vulnerability to progressive RAS. Mild to moderately severe obstructions seem to preserve the tubular transport costs.Funding provided by NIH Grant (HL16496‐32), 2007 APS Porter Physiology Fellowship and the Mayo Foundation.
Perinuclear formation of Reactive Nitrogen Species causes DNA damage in Methicillin‐resistant Staphylococcus Aureus induced sepsis.
Authors: Bansal Kamna , Connelly Rhykka L , Herndon David , Traber Daniel L , Enkhbaatar Perenlei 
Published: June 2021

RationaleMRSA commonly referred to as a 'super bug' because of its resistance to antibiotic therapy, is now a common infection encountered in hospitals and communities. We have previously shown that MRSA causes vascular hyperpermeability, multi‐organ system failure, and death in our ovine model of MRSA‐induced sepsis. We hypothesized that RNS may play a pivotal role in MRSA‐induced DNA damage and consequent cellular death.MethodsPulmonary epithelial cell (A549) were challenged with 105 cfu MRSA over a time course of 4 hrs then probed for markers of RNS (2,7‐Dichlorodihydrofluorescein [DCF] and 3‐Nitrotyrosine {3‐NT}), as well as poly ADP‐ribose (PAR), a marker of DNA damage, by confocal imaging and western blot analyses. Neuronal nitric oxide synthase (nNOS) and NADPH oxidase‐4 (NOX4) were localized by confocal microscopy.ResultsMRSA caused nNOS and NOX4 translocation to a perinuclear location, resulting in a 7‐fold increase in RNS (measured by DCF) at the perinuclear compartment compared to normal cells. MRSA also caused PAR (3.4 fold) and 3‐NT (4.8 fold) formation within 1h of MRSA exposure observed by both confocal and western blotting analyses.ConclusionsMRSA causes DNA damage in alveolar epithelial cells as result of perinuclear formation of RNS .
Effects of intermittent hypoxia on regulation of BDNF mRNA in the brainstem and spinal cord of MeCP2 mutants
Authors: Jenkins Victoria K , Balkowiec Agnieszka , Bissonnette John M 
Published: June 2021

Brain‐derived neurotrophic factor (BDNF) is necessary and sufficient for the expression of long‐term facilitation, a form of respiratory plasticity that is induced by intermittent hypoxia (IH). BDNF is a target gene for the transcription factor methyl‐CpG‐binding protein 2 (MeCP2), but its role in determining the regulation of BDNF transcripts after IH has not been determined.MeCP2 null and wild‐type male mice were exposed to three IH intervals (5 minutes of 21% O2, 5 minutes of 8% O2) followed by a 60‐minute post‐hypoxia rest. The ventral half of cervical spinal cord segments 3‐5, pons, and medulla were dissected. RNA was extracted and BDNF levels were evaluated by quantitative RT‐PCR. The IH‐induced increase in expression of transcript 4 in medulla of MeCP2 null mutants exceeded that in wild‐type mice. This transcript trends upward in pons, but stays constant in cervical spinal cord. The results suggest that MeCP2 modulates BDNF expression during IH.
Increased neuropeptide Y innervation in the airway epithelium of mice overexpressing Nerve Growth Factor
Authors: Dey Richard D , Batchelor Thomas P , Hoyle Gary W 
Published: June 2021

The neurotrophin, nerve growth factor (NGF), supports nerve growth and axon sprouting of sensory and sympathetic neurons. NGF is elevated in asthmatics and contributes to airway hyperresponsiveness and inflammation. Overexpression of NGF has been reported in lungs of transgenic mice by linking the NGF gene to the Clara cell secretory protein (CCSP) promoter. These mice overexpress catecholamines and the neuropeptide substance P. Since sympathetic nerves respond to NGF, we hypothesized that NPY might be elevated in the NGF‐CCSP mice. NGF‐CCSP and wild‐type mice were prepared for quantitative immunocytochemistry for neuropeptide Y (NPY) and the pan‐neuronal marker PGP 9.5. Nerve fiber density (NFD) of NPY (n=3) in epithelium of the NGF‐CCSP transgenic mice (1.28 + 0.26%) was significantly increased compared to the epithelium of wild‐type mice (0.09 + 0.012%). PGP 9.5 NFD (n=1) in the transgenic mice was also increased (2.86 %) compared to wild‐type (0.07%). These findings support two important conclusions. First, that NGF overexpression substantially enhances NPY innervation of airway epithelium, which is normally very low. Second, the increased PGP 9.5 innervation indicates that NGF‐induced nerve fiber sprouting and growth had occurred within the epithelium. The findings suggest that increased NGF release known to occur during development or environmental exposures may control airway epithelial innervation.Funded by NIH HL35812 and HL80566.
Effects of smoke exposure on neuropeptide Y‐containing nerves in airway of early postnatal mice
Authors: Wu Zhong.‐Xin , Johnson Jessica , Benders Katherine M. , Dey Richard D. 
Published: June 2021

Abundant epidemiological data show that maternal smoking during pregnancy or neonatal and infant periods increases the incidence of respiratory illnesses later in life. However, the underlying mechanism remains unclear. Neuropeptide Y (NPY) produces vasoconstriction of airway vasculature and our previous PCR array data shows that the NPY gene is enhanced by smoke exposure during early prenatal periods. The goal of this proposal is to study the effects of early postnatal smoke exposure on NPY airway innervation. New born mice were directly exposed to either smoke or filtered air for 1, 5 and 10 days (6 hours per day) and the density of NPY‐containing nerves in airway smooth muscle was measured by immunocytochemistry 16 hours after the last smoke exposure. NPY‐containing fibers were mainly found around blood vessels and airway smooth muscle. NPY nerve fiber density in airway smooth muscle were significantly increased from 0.88 0.14 to 4.81 0.68 after 5 days smoke exposure and from 0.69 0.11 to 3.46 0.42 after 10 days smoke exposure. 1 day smoke exposure increased NPY from 0.55 0.07 to 1.18 0.29, but difference was not significant. These data suggest that cigarette smoke exposure enhances NPY expression in airways of newborns.Funded By: NIH HL 35812 and NIH ES014618
Participation of central G‐alpha i2‐subunit proteins in blood pressure regulation and in countering salt‐sensitive hypertension
Authors: Wainford Richard David , Kapusta Daniel R 
Published: June 2021

These studies tested the hypothesis that central Gai/o protein pathways are involved in mediating the cardiovascular depressor responses to central a2‐adrenoceptor activation and in countering the development of hypertension to a high NaCl challenge.MethodsThe a2‐agonist guanabenz (50 μg) was administered by intracerebroventricular (i.c.v.) injection to conscious instrumented Sprague‐Dawley (SD) rats pre‐treated (24‐h) i.c.v. with saline or oligodeoxynucleotides (ODN) against Gai1,i2, i3 and ao subunits (25 μg/each). Mean arterial pressure (MAP) and heart rate were recorded and urine collected for 150‐min (10‐min periods). Separate animals were implanted with miniosmotic pumps delivering i.c.v. Gai2 ODN (25 μg/day) and maintained on normal 0.4% NaCl (NS) or high 8% NaCl (HS) chow for 21‐days prior to study.ResultsIn vehicle pretreated SD rats on NS, i.c.v. guanabenz elicited bradycardia, hypotension, diuresis and natriuresis. Selective central down‐regulation of Gai1, i2, i3 or Gao protein did not alter bradycardic or diuretic responses to i.c.v. guanabenz. Gai2 protein down‐regulation prevented the hypotension (peak δMAP [mmHg]; guanabenz, ‐19±2 vs. Gai2 ODN + guanabenz, ‐3±2, P<0.05) and natriuresis to guanabenz (peak δUNaV [ μeq/min]; guanabenz, 7.6±0.8 vs. Gai2 ODN + guanabenz, 2.2±1, P<0.05). When infused (21‐day) with i.c.v. Gai2 ODN, SD rats maintained on HS developed hypertension (MAP [mmHg]; NS + Gai2 ODN, 129±2 vs. HS + Gai2 ODN, 147±3, P<0.05).ConclusionCentral Gαi2 protein‐gated pathways mediate the hypotensive and natriuretic responses to i.c.v. guanabenz. Further, these data suggest a previously unknown novel role for central Gαi2 protein pathways in preventing the development of salt‐sensitive hypertension. DK43337, HL 071212, AHA 0855293E, P20 RR018766
Brief ACE Inhibition Produces Persistent Changes That Protect Heart but Not Kidney From L‐NAME Induced Damage
Authors: Hale Taben Mary , Robertson Susan , Burns Kevin D , deBlois Denis 
Published: June 2021

ACE inhibitors reduce LV mass and cardiovascular‐renal fibrosis. The present study investigates whether brief ACE inhibition in SHR provides long‐term protection to LV and kidney from L‐NAME‐induced damage.Adult SHR received the ACE inhibitor enalapril or tap water. One set of control (C2) and treated (E2) were sacrificed after 2 wks. The second set of control (C2+2) or treated (E2+2) SHR were sacrificed following a 2‐week washout and the final set of control (CL) and previously treated (EL) rats received L‐NAME (10 days) after washout period. At sacrifice, kidney and LV were weighed and formalin fixed.LV mass was significantly reduced by enalapril and this difference between control and treated persisted throughout the study. In response to L‐NAME, the total number of proliferating cells, interstitial fibrosis, number of macrophages was decreased in the LV of SHR previously treated with enalapril. In contrast there was no difference in the glomerular size or degree of glomerulosclerosis.The present study suggests that brief ACE inhibition may confer some protection against heart but not kidney disease, even in the absence of continued treatment.