bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refeeding‐induced thyrotropin (TSH) secretion: A possible role for PYY3–36?
Authors: Costa‐e‐Sousa Ricardo Henrique , Oliveira Karen Jesus , Almeida Norma Aparecida , Souza Luana L , Cedraz‐Mercez Pedro , Cabanelas Adriana , Pazos‐Moura Carmen Cabanelas 
Published: June 2021

Low levels of PYY3–36, TSH and thyroid hormones are adaptative mechanisms to fasting state. Serum TSH increased after PYY3–36 peripheral administration in fasted rats. Since PYY3–36 is secreted by intestinal cells after a meal, it could be involved in refeeding‐induced TSH secretion. Thus, we aimed to investigate how PYY3–36 stimulates TSH secretion and its role in TSH secretion after refeeding. Pituitary glands of fasted rats showed no change in TSH secretion when incubated during 2h in presence of PYY3–36 at different concentrations (10−10, 10−8 and 10−6 M). Serum TSH decreased 15 minutes after PYY3–36 injection (0.1nmol/rat) into the 3rd ventricle of 72h fasted rats (2.02±0.29 vs 1.03±0.1 ng/mL, P<0.01). Reduced dose (0.01nmol) did not modify serum TSH (1.67±0.20 vs 1.95±0.16 ng/mL; control vs PYY3–36). Anyway, if PYY3–36 has a role in refeeding‐induced TSH secretion, TSH level should increase quickly after refeeding. While 1h refeeding did not modify serum TSH (0.98±0.18 ng/mL), 3h increased it, relatively to fasted group (2.99±0.40 vs 1.15±0.23 ng/mL, P<0.001). Therefore, it is possible that PYY3‐36 may play a role in refeeding‐induced TSH increase. However, PYY3–36 does not act directly at the pituitary to modulate TSH secretion of fasted rats. In addition, data do not support the hypothesis that PYY3–36 stimulates TSH secretion by direct hypothalamic action.CNPq, FAPERJ.
Central fatigue induced by intracerebroventricular infusion of AT1‐receptor blocker is influenced by serotonin content in preoptic area and hypothalamus
Authors: Leite Laura Hora Rios , Soares Danusa Dias , Marubayashi Umeko , Coimbra Cândido Celso 
Published: June 2021

We previously showed that central angiotensinergic transmission plays an important role on thermoregulation and metabolic adjustments during exercise by increasing heat dissipation and modulating heat production. To asses the effect of central angiotensin AT1 receptor blockade by losartan (Los) on serotonin content in preoptic area (POA) and hypothalamus (HP), Wistar rats were submitted to exercise until fatigue after intracerebroventricular (icv) injection of 2 μL of Los (60 nmol, n=6) or 0.15 M NaCl (Sal, n=6). Time to fatigue (TTF) and workload (W) were analyzed. At fatigue, animals were decapitated, brains were removed and POA and HP were dissected and frozen in dry ice. Serotonin (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) were measured by HPLC. Los animals showed a 35% and 32% decrease in TTF and W, respectively, when compared to Sal‐treated rats. These animals showed higher levels of 5‐HT and 5‐HIAA in POA (5‐HT: 0.4±0.05 ng/mg, Los vs 0.09±0.02 ng/mg, Sal; 5‐HIAA: 2.6±0.5 ng/mg, Los vs 0.8±0.2 ng/mg, Sal, p< 0.05) and HP (5‐HT: 0.2±0.02 ng/mg, Los vs 0.06±0.03 ng/mg, Sal; 5‐HIAA: 2.4±0.6 ng/mg, Los vs 1.2±0.4 ng/mg, Sal, p< 0.05). An inverse correlation between W and 5‐HT content in the POA and HP was also found (POA: r= 0.67; HP: r= 0.63, p< 0.05). Our data suggest that central fatigue induced by AT1 receptor blockade is related to an increase in 5‐HT content in the POA and HP.Supported by: CNPq, FAPEMIG and CAPES.
Differentiation of human circulating fibrocytes into chondrocytes and osteoblasts
Authors: Choi Young Hun , Burdick Marie D. , Strieter Robert M. 
Published: June 2021

Fibrocytes are a distinct population of blood‐borne progenitor cells with fibroblast‐like features. It has also been proposed that fibrocytes have multipotency of mesenchymal stem cells. Recently Kurt Hong et al. showed fibrocytes differentiated into adipocytes and fibroblasts (Hong et al. 2007. J. Biol. Chem., 282: 22910–20). We further investigated whether fibrocytes can differentiate into chondrocytes and/or osteoblasts. Under the existence of 10 ng/ml TGF‐beta3, fibrocytes differentiated into chondrocytes, proved by Safranin‐O staining for type II collagen. Von Kossa calcium staining showed that the incubation of fibrocytes with osteogenic medium, containing dexamethasone, ascorbate, and beta‐glycerophosphate, resulted in differentiation of fibrocytes into osteoblasts. In conclusion, circulating fibrocytes have multipotency of adult stem cells, and could be useful for regenerative therapy.Supported by NIH Grant HL‐66027.
Arginine magic: Arginine kills tumor cells when presented in saline
Authors: Shukla Jyoti , Thakur V.S. , Poduval T.B. 
Published: June 2021

There has been no anti‐cancer formulation so far, which is sufficiently effective for the treatment of cancer using an endogenous molecule. Various scientists have attempted to describe the complex role of arginine in cancer biology and treatment. Nobody has yet looked at the non‐substrate actions of arginine, to act as a Biological Response Modifier through its chemical structure. Arginine containing peptides have been used as delivery vectors to carry payloads of drugs. The results indicate that guanidinium group is critical for the translocation process. Based on the above, we hypothesized that pharmacological doses of L‐arginine (LA) when delivered in saline could interact with tumour cells more efficiently.Various tumor cell lines derived from mouse and human when incubated with LA, D‐arginine (DA) in pharmacological doses in PBS, caused the death of tumor cells, as assessed by the membrane integrity test, trypan dye exclusion test and MTT assay. There was complete destruction of cell structure (Fig.1). DA had better anticancer ability as it could inhibit the tumor growth at lower concentration. The anticancer property of LA is not accompanied by any toxicity to the red blood cells or NIH 3T3 cells. L‐lysine and agmatine did not offer any antitumor activity. Arginine administered in PBS could also cure the mice of the tumor transplanted into the peritoneum (Fig. 2). These findings provide a previously unrecognized beneficial effect of guanidinium group containing compounds in killing the tumor cells and thus provide new potential approaches for therapeutic development of arginine in tumor therapy.
The hepatic aquaporin 9 (AQP9) expression is regulated in response to castration and PPARα‐ agonist treatment
Authors: Lebeck Janne , Skowronski Mariusz Tomasz , Praetorius Jeppe , Frøkiær Jørgen , Nielsen Søren 
Published: June 2021

It has previously been shown that male rats have higher hepatic expression of AQP9 than female rats (Nicchia et al, J Histochem Cytochem, 2001). The regulation of hepatic AQP9 has also been related to PPARα (Patsouris et al, J Clin Invest, 2004). This study aims to investigate the role of castration and PPARα–agonist (Wy 14643) administration in regulation of hepatic AQP9 protein expression in male rats. In castrated rats, immunoblotting showed a 1.7 fold increase in hepatic AQP9 (p < 0.01). This finding was confirmed by immunohistochemical analysis. Serum testosterone was decreased in the castrated group (p < 0.01), while serum insulin was 1.0 ± 0.3 and 1.9 ± 0.6 in castrated and controls, respectively, however this was not statistically significant and plasma glucose levels remained unchanged. In rats treated for 10 days with Wy 14643 (3 mg/kg/day), immunoblotting showed a 2.6‐fold decrease in the expression of hepatic AQP9 (p < 0.001). Immunohistochemical analysis revealed a marked decrease of AQP9 in the periportal zone, whereas AQP9 expressed in the perivenous zone appeared unchanged. There were no changes in serum insulin or glucose levels. We conclude that hepatic AQP9 protein expression increases in response to castration in male rats, whereas treatment with PPARα–agonist results in a marked decrease and redistribution of hepatic AQP9 protein.Supported by the Danish National Research Foundation
Deletion of PKCalpha in mice attenuates the thrombin‐induced increase in lung vascular permeability
Authors: Vandenbroucke Emily Elizabeth , Vogel Stephen , Gao Xiaopei , Komarova Yulia , Malik Asrar B 
Published: June 2021

We addressed the role of protein kinase Cα (PKCα) in signaling the increase in lung vascular permeability induced by the mediator thrombin. We used PKCα knockout mice to determine the effect of PKCα deletion on changes in endothelial permeability and adherens junction proteins. We determined microvessel filtration coefficient (Kfc) using the isolated‐perfused mouse lung preparation. Stimulation with PAR‐1 agonist peptide (10 μM) increased Kfc 50% less in the knockout mice than control wild type mice. We quantified vascular endothelial (VE) cadherin levels in mouse lung endothelial cells (MLECs) by Western blot analysis. Thrombin rapidly diminished VE‐cadherin levels in MLECs. PKCα deletion abrogated the VE‐cadherin disruption induced by thrombin. As PKCα activation was known to inhibit Akt, we observed higher Akt activity in PKCα‐deleted MLECs. We also observed that activated PKCζ was markedly increased in PKCα‐deleted MLECs, suggesting compensatory activation of PKCζ. The data demonstrate that PKCα is required to elicit the increase in lung vascular permeability. The mechanism of PKCα‐mediated increase in vascular permeability may involve signaling at the level of VE‐cadherin that promotes the disassembly of adherens junctions.This study is supported by NIH # HL45638
Angiotensin‐(1–7) opposes agonist‐induced constriction in endothelium denuded rat aortic rings via NO and PI3‐Kinase pathways
Authors: Allahdadi Kyan James , Leite Romulo , Webb R. Clinton , Santos Robson A. S. 
Published: June 2021

Background: Angiotensin‐(1–7) [Ang‐(1–7)] is a potent vasodilator eliciting its effects primarily through endothelial derived factors. However, a direct effect of Ang‐(1–7) on the vascular smooth muscle (VSM) has not been fully investigated. This study tested the ability of Ang‐(1–7) to regulate agonist‐mediated VSM constriction in the absence of the endothelium.Methods and Results: Endothelium denuded thoracic aortic rings (3 mm) from male Wistar rats (250–300g) were used in this study. Pretreatment with Ang‐(1–7) (10−5 M) significantly attenuated both Ang II and phenylephrine (PE) concentration response curves (10−10–10−6 M). This attenuated constrictor response was abolished by incubation with the selective Ang‐(1–7) receptor antagonist, A779 (10−5 M), the non‐selective nitric oxide synthase (NOS) inhibitor, L‐NAME (10−4 M), or the phosphatidylenositol 3‐kinase (PI3Kinase) inhibitor, LY29004 (10−5 M).Conclusion: Our data suggest that Ang‐(1–7) activates its receptor and signals through NO derived from NOS isoforms within VSM. Additionally, we provided evidence that this opposed vasoconstrictor response involves the PI3‐kinase pathway. We suggest that this endothelium independent Ang‐(1–7)‐induced attenuation of the agonist‐mediated constriction of the VSM is an important mechanism by which Ang‐(1–7) participates in vascular reactivity and consequently blood pressure regulation.
PKG and SRF, Important Regulatory Factors Involved with Vascular Smooth Muscle Gene Expression
Authors: Brown Felricia Moyer , Choi Chung‐Sik , Lincoln Thomas M. 
Published: June 2021

Vascular smooth muscle cell (VSMC) gene expression is altered in vascular diseases such as atherosclerosis. The NO/cGMP pathway appears to prevent the fibro‐proliferative response of VSMC in such instances. Cyclic GMP‐dependent protein kinase (PKG), the down‐stream mediator of NO/cGMP signaling, has been shown to regulate VSMC phenotype and stimulate VSMC gene expression. Serum response factor (SRF), a transcription factor associated with many signaling pathways including smooth muscle‐specific gene expression stimulates VSMC gene expression. The key objective of this study was to determine if PKG regulates SRF expression or translocation into the nucleus in VSMC. Results obtained: Primary cultures of VSMC were used to test whether PKG‐I activity increases SRF expression or translocation in VSMC. Down regulation of endogenous PKG‐I using siRNA decreased PKG‐I expression, but did not affect the overall level of SRF expression in VSMC. Over‐expression of PKG‐I caused increased SRF to be translocated to the nucleus, coincident with increased expression of smooth muscle myosin heavy chain. These effects were reversed in VSMC over‐expressing PKG‐I along with siRNA treatment. Conclusion: Up‐regulation of PKG‐I expression in VSMC may increase VSMC specific gene expression by increasing the SRF level in the nuclear compartment.Supported by NIH grants: 5T32HL076125 and RO1HL53426
PPARgamma Antagonists Attenuate Hypoxia‐induced Pulmonary Hypertension
Authors: Crossno Joseph T , Sullivan Timothy M , Morris Kenneth G , Klemm Dwight J 
Published: June 2021

Rationale: Peroxisome proliferators‐activated receptor γ (PPARγ) agonists attenuate hypoxia (Hx)‐induced pulmonary artery (PA) remodeling. The present study tested the hypothesis that PPARγ antagonists exacerbate Hx‐induced PA remodeling.Methods: Wistar‐Kyoto rats were randomized to normoxia (Nx) and hypobaric Hx and treated with or without the PPARγ agonist Rosiglitazone (ROSI) or the PPARγ antagonists GW9662, T0070907, or SR‐202 for 3 weeks.Results: PA catheterization performed on Hx‐ROSI treated groups had no attenuation of Hx‐pulmonary hypertension (PH) vs Hx‐Controls. However, PPARγ antagonist treatment resulted in a decrease in PA pressures in response to chronic Hx [p < 0.05]. PA morphometric analysis demonstrated a marked decrease in proximal and distal PA remodeling vs Hx‐Controls [p = 0.003]. Right ventricular hypertrophy [RV/(LV+S)] was decreased in both the Hx‐PPARγ agonist and antagonist treated groups [p = 0.05]. The decrease in PA remodeling and RV hypertrophy was due to inhibition of proliferation without an increase in apoptosis.Conclusions: PPARγ antagonists GW9662, T0070907 and SR‐202 exert a significant vascular protective effect on Hx‐induced PH and PA remodeling.
Venous compliance in hypertensive adults
Authors: Delaney Erin P , Stillabower Michael E , Farquhar William B 
Published: June 2021

Venous hemodynamic function is altered in animal models of hypertension. Lowered peripheral venous compliance (VC) may lead to a “centralization” of blood volume and contribute to the development of hypertension.Purpose:To investigate the effect of hypertension on VC in young and older adults. We hypothesized that limb VC would be lower in hypertensive (HTN) than normotensive (NTN) adults.Methods:VC was measure in 15 young NTN (YN; 23±1 years), 10 young HTN (YH; 23±1 years), 9 older NTN (ON; 65±1 years), and 11 older HTN (OH; 64±1 years) adults via venous occlusion plethysmography in the calf and forearm at baseline, during a cold pressor test, and after administration of nitroglycerin. Pressure‐volume relationships from a cuff deflation protocol were determined with quadratic regression; regression parameters were used to calculate VC at a pressure of 20 mmHg. Data were analyzed with an ANOVA.Results(mean±SE): There were no baseline differences in VC between YN and YH (Arm: YN=0.064±0.004 vs. YH=0.062±0.005 ml/dl/mmHg; Leg: YN=0.070±0.006 vs. YH=0.064±0.005 ml/dl/mmHg) or ON and OH (Arm: ON=0.046±0.004 vs. OH=0.049±0.004 ml/dl/mmHg; Leg: ON=0.050±0.005 vs. OH=0.050±0.006 ml/dl/mmHg). VC did not change from baseline in response to stressors (data not shown).Conclusion:These data indicate that otherwise healthy HTN adults do not demonstrate a reduction in peripheral VC below aged‐matched NTN adults.
Plasma membrane depolarization‐induced ERK activation: role in regulating paracellular permeability of the proximal tubular epithelium
Authors: Waheed Faiza , Speight Pam , Kapus Andras , Szaszi Katalin 
Published: June 2021

Both physiological and pathological conditions, including apical ion transport, hypoxia, oxidative stress, and ATP depletion can alter the membrane potential of epithelial cells. We have previously shown that membrane depolarization induces Rho‐Rho kinase (ROK) mediated phosphorylation of myosin light chain (MLC) in proximal tubule epithelial cells and elevates paracellular permeability. Here we show that the permeability increase was absent in cells stably expressing a non‐phosphorylatable, dominant negative MLC. Depolarization, elicited by high extracellular [K+],– or ouabain, an inhibitor of the Na+/K+ ATPase, also activated the Ras‐Raf‐MEK‐ERK pathway. ERK activation was fast, reversible and independent of intracellular Ca2+. Immunofluorescent staining revealed that ERK translocates to the cell periphery. The MEK inhibitor PD98059 reduced the depolarization‐induced rise in paracellular permeability. Interestingly, PD98059 also mitigated the depolarization‐induced MLC phosphorylation, raising the possibility that ERK affects paracellular permeability by contributing to increased contractility.In summary, our data suggest that cell contractility, regulated by the Rho‐ROK and the Ras‐ERK pathway might play a key role in epithelial barrier dysfunction caused by sustained depolarization.Support: NSERC, Banting Foundation and Kidney Foundation of Canada.
Could differential expression of Apolipoprotein E (Apo E) in the alveolar epithelium be responsible for redox regulation of ENaC in type 1 and type 2 cells?
Authors: Helms My N , Self Julie L , Eaton Douglas C 
Published: June 2021

We studied redox regulation of ENaC in the alveolar epithelium by patch clamping type1 and type2 cells in situ from a lung slice preparation. We found that type1 and type2 cells respond to nitric oxide (NO) donors differently. In 18 patch clamp recordings of type2 cells accessed in situ, 15μM NO‐donor, significantly decreased ENaC NPo from (control) 1.38±.26 to 0.82±.16 (p<0.05). Nitric oxide, however, does not alter lung ENaC activity in type1 cells; whether 15μM or 500μM NO‐donor was applied to type1 cells, ENaC activity did not significantly change from control NPo values from .63±.12; n=15. Using a cell culture model of the alveolar epithelium, we found that type1 cells have elevated levels of O2− compared to type2 cells, which suggests that differences in the cellular response to NO may be due to the oxidative state of pneumocytes. Apolipoprotein E, a 34 kDa plasma protein involved in the transport of cholesterol and other lipids, has been shown to be specifically expressed in type 1 cells (and not type 2 cells), and is up‐regulated in hyperoxic lung (Chen et al. 2006). Because of their known role in lipid transport, future studies are aimed at determining the effects of Apo E on lung ENaC under oxidative stress using single channel patch clamp analysis.This work was supported by NIH grants HL071621‐01 and DK37963‐16 awarded to DCE and the Parker B. Francis Fellowship to MNH.
IMPACT OF HYDROGEN SULFIDE (H2S) ON CAT CAROTID BODY (CB) FUNCTION
Authors: Fitzgerald Robert Schaefer , Shirahata Machiko , Kostuk Erik , Olson Ken 
Published: June 2021

Current reports identify acetylcholine (ACh) and ATP as two excitatory transmitters in the cat and rat CBs. This study explored whether H2S could function as a neuromodulator, by measuring the release of ACh and ATP in response to the presence of H2S. The response to a KATP channel agonist, pinacidil, was also tested because in vascular tissues H2S is thought to act on that channel. In vascular tissue H2S is reported to mimic the effects of hypoxia. Harvested cat CBs were prepared for incubation in Krebs Ringer bicarbonate solutions (KRB) at 37°C using standard procedures consonant with the regulations of the Institutional Animal Care & Use Committee. ACh was measured with HPLC‐ECD methods; ATP, detected by a bioluminescence reaction. Positive immunohistochemical signals for Kir6.1 and SUR1 subunits of the KATP channel appeared in glomus cells (GC). The release of ACh from 2 cat CBs incubated in KRB made 100 μM Na2S (precursor of H2S) and bubbled with 30% O2/5%CO2 for 6 min significantly dropped to 60% of the control; the reduction in ATP was small and not significant. ACh release in response to KRB made 100 μM pinacidil and bubbled with 30% O2/5%CO2 for 6 min was significantly reduced to 42% of the control; ATP was reduced to 65% of the control. The data suggest the presence of the KATP channel in GCs; ACh and ATP release is affected by Na2S.NHLBI:HL 05712–14, HL 72293.
Prediction of cardiorespiratory fitness without exercise testing in low back pain patients
Authors: Ivan Duque , Frederico Arango , Alain Duvallet 
Published: June 2021

Cardiorrespiratory fitness is a capacity to perform, through body adaptations and responses, dynamic activities of moderate to high intensity using large muscle groups, during long time. It determines an important part of possibilities to perform activities of daily living and is closely related with health and quality of life. The measurement of the maximal oxygen uptake (VO2max) as a parameter of this fitness is useful for educating about the physical conditioning and in prescription and control of fitness programs in sick and healthy subjects.The aim of the study was to develop a regression equation to predict VO2max based on non‐exercise data in patients with chronic low back pain (CLBP). All patients (N=70) achieved a maximal graded exercise test with measured VO2max (30.8 ml.kg−1.min−1 +/− 7.7). The regression model included as non‐exercise data, the patient's sex, body mass index (BMI) and intensity of sports activities (IPAS). Multiple linear regression generated the following formula (R2 = 38.3, SEE = 6.08 ml.kg−1.min−1): VO2max (ml.kg−1.min−1) = 35.337 − 0.475 * BMI + 0.155 * IPAS + 7.976 * sex (women = 0 and men =1)The Durbin Watson statistic demonstrated inexistence of problems with serial autocorrelation (D–W = 1.86). The K–S normality test demonstrated that the errors are distributed normally. This study provides a relatively precise non‐exercise regression model to predict VO2max in CLBP patients.
Female gender is associated with decreased oxidative stress and increased insulin‐stimulated glucose uptake in skeletal muscle in TGR(mRen‐2)27 rats
Authors: Lastra Guido , Manrique Camila , Rehmer Nathan , Morris Mathew , Appesh Lama , Nusair Maein , Whaley‐Connell Adam , Ferrario Carlos , Sowers James R 
Published: June 2021

The transgenic Ren‐2 rat is a model of enhanced Renin Angiotensin Aldosterone System activity, which exhibits insulin resistance, hypertension, and microalbuminuria. We investigated gender differences in the production of Reactive Oxygen Species (ROS) and NAPDH oxidase activity in 8 to 11 weeks old Ren 2 rats and age‐matched SD rats. ROS production was determined by photon emission in the presence of lucigenin and NADPH. Results are presented as mean ± SEM, and unpaired t test and ANOVA were used as appropriate. SBP was similar between males and females (170.5 ± 16.21 vs 180.4 ± 8.61 mmHg). In insulin‐sensitive soleus muscle, NAPDH oxidase activity was higher in Ren 2 males compared to females (6.378 ± 0.41 vs 4.98 ± 0.27 mOD/min/mg p <0.05), while it did not differ between SD males and females (4.1 ± 0.24 vs 4.22 ± 0.47 mOD/min/mg p = 0.83). No significant differences in NAPDH oxidase activity were found in aorta, kidney or left ventricle. ROS production in soleus muscle was lower in Ren‐2 females compared to males (102.69 ± 4.48 RLU/s/mg vs 170.69 ± 11.33, respectively. p=0.025). Insulin stimulated glucose uptake was higher in Ren‐2 female compared to males (0.655 ± 0.057 vs 0.195 ± 0.0531 nmol/mg) Our findings suggest that female gender may be protective against oxidative stress and leads to increased insulin sensitivity in skeletal muscle in the Ren‐2 rat model.Funded by NIH 1R01‐HL073101‐02, VA Merit System 0018.