bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Decision Rules for Lot Quality Assurance Sampling on an Assessment of Micronutrient Program Coverage
Authors: Appelgren Kristie Elizabeth , Sullivan Kevin , Serdula Mary , Flores-Ayala Rafael
Published: June 2021

Lot quality assurance sampling (LQAS) is a sampling method that assesses small areas to determine if key goals of public health programs have been met. LQAS was used to monitor a new micronutrient powder (MNP) distribution program in Country X. LQAS decision rules (DR) were used to classify districts as having adequate or inadequate coverage with respect to three criteria: goal coverage, the lower limit of acceptable coverage, and the coverage level above which further intervention was not cost‐effective. There is controversy in recent literature between two approaches to DR selection: the first balances coverage goals with program expense, while the second prioritizes detection of low‐coverage districts. This study compared results from both approaches to DR selection. In each of 48 districts, 24 households were randomly selected. Goal district coverage for MNP use was 70%. Using the first approach, a DR of 16 households (66.7% of each district sample) defined adequate coverage. Using the second approach, a DR of 20 (83.3%) was used. DRs were selected using FANTA‐II software. Using the first DR, coverage was inadequate in 14.6% of districts, compared to 47.9% using the second DR. Choice of DR substantially altered the number of districts in need of more resources to improve coverage. The first approach allows this new program with limited resources to focus on the worst‐performing districts. The second approach ensures that passing districts have met the coverage goal and is useful once a minimal effective level of coverage is determined. The key to DR selection is examination of the current needs of each program.
Evaluation of risk factors of obesity in school‐age children attending public and private schools in Mexico
Authors: Romano Diana E , del Carmen Caamaño Maria , Garcia Olga P , Ronquillo Dolores , Arellano Rocio , Rosado Jorge L
Published: June 2021

The objective of this cross‐sectional study was to evaluate the association between mother's BMI and educational level, children's diet and type of school with children's overweight and obesity. A total of 1102 children (557 boys and 545 girls), 5–12 years, from 7 random private and public schools of Queretaro, Mexico, participated in the study. Weight, height, waist circumference, and body fat% were determined in all the children. Diet was evaluated with three 24hr recall. Height and weight of children's mother were measured, and their educational level was evaluated using a validated questionnaire. Forty four percent of children and 71% of mothers were either overweight or obese. In logistic regressions, the risk of being overweight or obese was greater among children attending public schools (OR=2.69, 95%CI 1.438–5.029). Children of mothers with a high education level or with a high a BMI had a higher risk of overweight or obesity (OR=2.59, 95%CI 1.33–5.043; OR=4.53, 95%CI 2.185–9.396, respectively). Also, children with low carbohydrate intake (<63% of total energy intake) had a higher risk of overweight/obesity (OR=3.89, 95%CI 1.343, 11.061). In conclusion, risk factors of overweight or obesity in this population included low carbohydrate intake, public school attendance, mother with a high BMI or mother with a high education level. CONACYT
Infant and young child feeding in Mexico: National Health and Nutrition Survey 2006 and changes from 1999
Authors: de Cosío Teresita González , Escobar Leticia , González Luz Dinorah , Reyes Horacio , Rivera Juan
Published: June 2021

We present evidence of infant & young child feeding practices (IYCFP) in Mexico using 2006‐WHO indicators (WHO‐I). Data from the last 2 national nutrition surveys (1999 & 2006) were used.

Subjects

women aged 12–49 y & their < 2 y child; n=2953 for 2006 & 3191 for 1999. Median lactation duration (MLD) and % of WHO‐I estimated with status‐quo method. Age of introduction (AI) to 7 food groups (FG) estimated (Kaplan‐Meier method). IYCFP analyzed by region, urban/rural location, socioeconomic & characteristics.

Results

MLD increased: 9.7–10.4 mo from 1999–2006, but decreased in indigenous populations: 17.4–14.6 mo. Proportion of exclusively breastfed infants <6 mo was 20% in 1999 & 22.3% in 2006; 66.2% of children 6–23 mo consumed Fe rich foods in 2006. Most lactation indicators decreased in the rural and indigenous groups from 1999–2006. Children in the Program OPORTUNIDADES had better IYCFP overall than population not enrolled. AI of the 7 FG: water 3 mo; non‐human milk, cereals & legumes, & animal sources 5 mo; non‐nutritive liquids, fruits & vegetables 6 mo; nutritive liquids 8 mo. Results show the poor lactation performance in Mexico, as well as untimely IYCFP. It is necessary to design programs aimed at protecting and promoting human lactation and adequate complementary feeding, especially for the poorest and indigenous groups. Research supported by Center on Nutrition and Health, National Institute of Public Health.
Anti‐asthmatic properties of Bio‐Rice in OVA‐induced asthmatic mice
Authors: Tung Hsiang-Yuen , Kao Yu-Yu , Yu Chi-Cheng , Lin Ting-An , Yang Jo-Hsuan , Huang Hui-Yu
Published: June 2021

From the long time, polysaccharides and saponin have been used in the traditional medicine to treat several diseased conditions including inflammatory disease. In this study, we investigated the anti‐asthmatic effect of Bio‐Rice, a rich source of polysaccharides and saponin in OVA‐induced asthmatic mice model. Forty OVA‐induced asthmatic BALB/c mice were equally divided into four groups, including control, and different concentrations of Bio‐Rice treated groups (1X, 2X and 4X). Respective mice received Bio‐Rice for 8‐week. The anti‐asthmatic effect of Bio‐Rice was determined by observing eosinophil recruitment, airway hyper‐responsiveness, Th2 cytokine and IgE levels. The Bio‐Rice treatment effectively reduced the percentage of eosinophils in BALF when compared to the level in OVA‐induced mice. Bio‐Rice also suppressed AHR‐induced by aerosolized methacholine. Furthermore, Bio‐Rice treatment suppressed the serum IgE level and decreased Th2 cytokines in the supernatant of cultured splenocytes. These results suggest that Bio‐Rice may have therapeutic potential against asthma.
Diet, Nutrition, and Botanicals in Minimizing the Risk of Alzheimerˈs Disease
Authors: Dey Ipsita , Chitre Deepa
Published: June 2021

Alzheimer's disease (AD) is a progressive neurodegenerative disease commonly afflicting the elderly. In the United States, it was the 7th major cause of death in 2010, claiming almost 5.3 million lives. The paucity of FDA approved drugs, their modest benefits, and serious adverse reactions are of utmost concern. Besides novel therapies currently being researched, proper diets, nutrition, functional foods, and botanicals are also under investigation for future therapies. In order to gain current knowledge about herbal prospects for AD, we performed a web based literature search on the use of herbal extracts or plant based formulations and their neuroprotective effects in different preclinical and clinical studies. Interestingly, several reports showed promising evidence for the use of herbal supplements, which include, but are not limited to: ashwagandha, evening primrose, garlic, oriental ginseng, gingko, neem, rosemary, water hyssop, turmeric, and zedoary. However, larger well controlled studies with longer treatment periods are required to assess efficacy on cognition and memory, as well as other issues, such as contaminating pesticides and heavy metals which can aggravate the progression of AD.
Liver Morphologic Changes Induced by 1‐naphthyl methylcarbamate
Authors: Costa Eduardo Leitão , Cavalcanti Karen , Costa Miguel , Pereira Felipe , Souza Ivone , Cabrita Silvério
Published: June 2021

The chemical 1‐naphthyl methylcarbamate (1NC) belongs to a class of pesticides known as carbamates. This chemical substance can be produced by hydrolysis of the carbamate ester group with consequent degradation of the hydrolyzed fragments. It is moderately soluble in water, but has a good solubility in a large spectrum of organic solvents.

The objective of this study was to evaluate the liver morphologic changes associated with the ingestion 1‐naphthyl methylcarbamate. One group of ten male Wistar rats, 8 weeks old, was submitted to the administration of 1NC 60mg/liter in drinking water during 8 weeks. Another group of ten male Wistar rats, 8 weeks old maintained during 8 weeks with no manipulation was used as a control group.

All animals were sacrificed at the end of an 8 weeks period and a complete necropsy was performed. The slides of liver, stained by HE, were evaluated for morphologic lesions. In the group with 1‐naphthyl methylcarbamate some morphologic lesions were found, such as macrovesicular steatosis, some focus of stase with dilatation of sinusoids and small locals of necrosis. Mitotic figures were observed frequently. However, we did not observe focal hemorrhages, fibrosis, but only rare cases of cloudy swelling. In the control there was no significant lesions.

These results suggest that an acute 1NC intoxication can induce minimal liver morphologic changes.
Dexamethasone induces apoptosis of osteoblasts in culture by interference in cell adhesion complex
Authors: Naves Marcelo Andery , Paterno Josne Carla , Oliveira-Sales Elisabeth B , Caparbo Valéria F , Pereira Rosa R , Teixeira Vicente Paulo Castro
Published: June 2021

Adhesive interactions play a critical role in cell biology, influencing vital processes from proliferation to cell death. The objective of this study was to analyse the effect of DEX (dexamethasone) on the biology of osteoblasts and its influence on the expression of ILK and β1 integrin. Primary human osteoblast culture were treated with dexamethasone in 10−9M (physiological) and 10−6M (pharmacological) doses of DEX for 24 and 48 hours. Cell viability (MTT assay), adhesion (crystal violet assay), apoptosis (flow cytometry), expression and immunolocalization of β1‐integrin and ILK (western blot and immunofluorescence) were analyzed. It was observed that cell viability and adhesion were reduced in the cultures evaluated. In comparison with the control cultures, there was slightly less apoptosis in the cultures exposed to the physiological dose and considerably more apoptosis in those exposed to the pharmacological dose. In all treated cultures, protein expression of ILK was slightly higher than in the control cultures, whereas that of β1 integrin was significantly lower. Both proteins under study were co‐localized at the cell periphery in all cultures. Our results suggest that DEX causes osteoblast anoikis, probably due to decreased β1 integrin expression, which might have had a direct influence upon ILK, reducing its activation and preventing it from playing its characteristic anti‐apoptotic role.

Supported by FAPESP, CAPES
Melatonin as key factor on bone remodeling in animal models with perforating fracture
Authors: Kim Koo , Lee Seunghoon , Hong Yunkyung , Lee Minkyung , Hong Yonggeun
Published: June 2021

Bone remodeling is occurred continuously through closely coupled events of osteoclasts, bone‐absorption cells, osteoblasts, and bone‐formation cells in physiological environment. To assess the effect of melatonin on bone remodeling in the femur perforating fractured rats, 8‐week‐old Sprague‐Dawley (SD) rats were treated twice daily with melatonin (10 mg/kg) at 7:00 and 19:00 up to 21 days after surgery for fracture using by micro‐drill. We confirmed that melatonin treated group (MT) was significantly enhanced ALP (p < 0.01), Col‐1 and TRAP mRNA level (p < 0.05) at day 3 after surgery. Whereas vehicle group (Veh) was not at day 3, but significantly increased ALP (p < 0.01) and Col‐1 mRNA¡¡(p < 0.05) mRNA expression at day 14 after surgery. It was closely correlated with histological study in both groups suggesting that melatonin might be as stimulating factor to accelerate of bone remodeling and repair, and should be investigated more experiment afterward to figure out clinical relevant to human patients.
Disorder in functional phenotype of alveolar macrophages in influence of risk factors for chronic obstructive pulmonary disease (COLD): age‐ and genetic predisposition
Authors: Malyshev Igor Yu , Lyamina Svetlana V , Vedenikin Timofey Yu , Malysheva Elena V
Published: June 2021

The defining role of tobacco smoking as a risk factor of COPD is of no doubt. However, there are still some unanswered questions. Do genetic determination and age‐related changes of macrophage's phenotype contribute to the development of lung pathology? Does alveolar macrophageˈs phenotype change with tobacco smoking? We modeled COPD in mice of different genetic strains (C57 and BALB/c) by tobacco smoke and studied phenotypes of alveolar macrophages. High production of NO is an indication of M1 phenotype; low production of NO after stimulation with LPS is an indication of M2 phenotype. It was shown that 1) there is a genetic predisposition to the influence of tobacco smoke, associated with proinflammatory M1 phenotype of macrophages; 2) aging promotes macrophages phenotype transformation towards antiinflammatory M2 which is more expressed in macrophages of mice with initially genetically determined M1 phenotype (C57), and 3) inhalation of tobacco smoke enhances age‐dependent transformation of macrophages aside M2 phenotype, that is also more expressed in macrophages of mice with genetically determined M1 phenotype (C57).

Grant #x00039A; No#x0003A0;811 Federal Special Program of Russia 2009–2013.
Induction of apoptosis in HepG2 cells by methanol extract of Ulmus pumila
Authors: Ghosh Chiranjit , Hwang Seong-Gu
Published: June 2021

Ulmus pumila. L is commonly used as a traditional Chinese medicine for treating edema, mastitis, gastric cancer and inflammation. In this study, we examined apoptosis of HepG2 cells induced by methanol extract of Ulmus pumila (UP), and the mechanism underlying apoptosis was also investigated. UP inhibited proliferation of HepG2 cells in dose and time dependent manner. Treatment of HepG2 cells with UP (50– 400 mg/ml) for 24 and 48 h led to a significant dose‐dependent increase in the percentage of cells in sub‐G1 phase by analysis of the content of DNA in cells. Immunoblot analysis showed that UP stimulated the apoptotic factors bcl‐xl, caspase‐3 and PARP in HepG2 cells. The results indicate that UP induces programmed cell death (apoptosis) in HepG2 cells and can be a potential therapeutic agent for treatment of hepatocellular carcinoma.
Arterial stiffness and hypertension in diet‐induced obese mice
Authors: Seta Francesca , Shiang Tina , Weisbrod Robert , Chauhan Pratibha , Bajpai Saumendra , Reinhart-King Cynthia , Cohen Richard
Published: June 2021

BACKGROUND

Arterial stiffness (AS) may contribute to increased blood pressure (BP) during aging and obesity and is an independent predictor of cardiovascular complications.

AIMS

To elucidate the molecular mechanisms of arterial stiffness and its relationship to the development of hypertension in a model of diet‐induced obesity.

METHODS AND RESULTS

C57BL/6J mice fed high fat‐high sucrose diet (HFHS), showed increased fat mass, body weight and insulin resistance compared to normal diet (ND). Pulse wave velocity (PWV), the speed of pressure waveform propagation along the aorta used as index of AS, increased by 2.5‐fold after 2 mos HFHS and remained elevated thereafter while BP, measured by radiotelemetry, increased only after 8 mos HFHS. Microalbuminuria, an index of renal dysfunction, developed after 4 mos HFHS. Aortic wall thickness and renin increased after 2 mos HFHS suggesting that renin‐angiotensin‐aldosterone system (RAAS) may contribute to AS in advance of hypertension. Stiffness modulus of aortic extracellular basal membrane, determined in vitro, was increased at 8 mos HFHS.

CONCLUSIONS

In diet‐induced obese mice, AS precedes the development of hypertension and kidney dysfunction. Our results suggest that RAAS may contribute to structural changes in aortic smooth muscle, as evidenced by aortic wall thickening and extracellular basal membrane stiffening, causing AS.
Substrate channeling of retinoic acid between cellular retinoic acid binding proteins (CRABPs) and CYP26 enzymes
Authors: Isoherranen Nina , Peng Chi-Chi , Yeung Catherine K , Lutz Justin D
Published: June 2021

CYP26s metabolize all‐trans‐retinoic acid (atRA) efficiently. In cells atRA is bound to two binding proteins, CRABP‐I and CRABP‐II (Kd<1nM). CRABP‐II channels atRA to nuclear retinoic acid receptors but the effect of CRABPs on CYP26 mediated metabolism of atRA has not been characterized. The aim of this study was to determine whether CRABP‐I and/or ‐II channel atRA directly to CYP26s. Using holoCRABP‐II as a substrate and with 2‐fold excess of apoCRABP, atRA hydroxylation by CYP26B1 was observed at similar rate but metabolism by CYP3A4 and CYP2C8 was completely eliminated when compared to free atRA. With holoCRABP‐I atRA metabolism by CYP26B1 was decreased by 50% (in presence of apoCRABP) and abolished by CYP3A4 and CYP2C8. Using isotope dilution with atRA‐D5 or atRA bound to CRABP‐I and CRABP‐II an equal ratio of labeled and unlabeled products was obtained demonstrating that CYP26B1 can obtain its substrate directly from CRABPs. holo‐CRABP‐I and holoCRABP‐II inhibited CYP26B1 mediated 9cis‐RA hydroxylation with a 100nM IC50 suggesting that CRABPs interact with CYP26B1 directly. Finally, excess of apoCRABP‐I decreased the Vmax of atRA hydroxylation but had no effect on Km suggesting that CRABP‐I interacts directly with CYP26B1. These results show that CRABP‐I and CRABP‐II channel atRA to CYP26B1 and demonstrate that ligand delivery to P450 enzymes by small binding proteins is possible.
Functional variants of the cysteinyl leukotriene 1 and cysteinyl leukotriene 2 receptors are associated with atopic asthma
Authors: Thompson Miles Douglas , Capra Valerie , Rovati Enrico , Stankova Jana
Published: June 2021

The atopy phenotype is reported to be a risk factor for asthma. Among the many loci that contribute to a genetic predisposition to asthma, the cysteinyl leukotriene receptor 1 (cysLT1) and 2 (cysLT2) genes have been important subjects of study because they are functionally and pharmacologically implicated in the atopy phenotype affecting many asthma subjects. In some populations we have found that the G300S variant of the cysLT1 receptor is associated with atopy. In an earlier association study, the M201V variant of the CysLT2 was implicated in atopic asthma. In this study we identify the statistical association of both the variants with the atopy phenotype. We propose a two hit hypothesis of atopy inheritance that involves the cysLT1 and cyLT2 variants. In vitro analyses are beginning to provide evidence that cysLT1 and cysLT2 interaction within the cell is possible and may represent a mechanism for the etiology of atopy in asthmatic populations.
Myotonic dystrophy protein kinase maintains organization of nuclear SC‐35 domains
Authors: Harmon Erin B. , Harmon Michelle L. , Larsen Tricia D. , Perryman M. Benjamin
Published: June 2021

Myotonic dystrophy (DM1) is a multi‐systemic disease caused by a triplet nucleotide repeat expansion in the 3′ untranslated region of the gene coding for myotonic dystrophy protein kinase (DMPK). DMPK mRNA transcripts containing CUG expansions accumulate in the nucleus, reducing the expression of DMPK protein in affected skeletal muscle. We have found that DMPK is a nuclear envelope (NE) protein that is critical to maintain NE integrity and is required for myotube formation. Over‐expression or depletion of DMPK disrupts nuclear structure, inducing abnormal aggregation of SC‐35 nuclear domains in C2C12 mouse myoblast nuclei. Since myogenic genes localize to SC‐35 nuclear domains during myotube differentiation, changes to SC‐35 domains would be expected to affect myogenesis. SC‐35 domains are also the intranuclear location of mutant DMPK mRNA aggregation in DM1 myocytes, so we also analyzed the transport of mRNA after SC‐35 domain aggregation. We visualized mouse DMPK mRNA in C2C12 myoblasts after SC‐35 domain disruption from human DMPK over‐expression. DMPK mRNA aggregates at disrupted SC‐35 domains, similar to the aggregation in DM1. These results suggest that DMPK regulates myogenic gene expression and the stability and structural organization of the nucleus, supporting a new model for DM1 pathophysiology based on a reduction of DMPK protein expression. This work was supported by grants from NIH (EBH, MPB).
Analysis of Lindane and Metabolites by HPLC‐UV‐Vis and MALDI‐TOF
Authors: Naidu Naga V , Smith-Baker Charlotte , Yakubu Momoh A
Published: June 2021

Lindane (hexachlorocyclohexane) is a persistent environmental toxicant and a known neurotoxicant. High levels of Lindane have been detected in postmortem human brain from Parkinson disease patients. Metabolism of Lindane produces several metabolites which are still imperfectly identified. Therefore, easy, fast and sensitive method to detect Lindane is highly desirable. We determined Lindane and its metabolites in urine by HPLC‐UV‐Vis and characterized it with MALDI‐TOF. Rats received Lindane (17.6 mg/Kg) or vehicle orally for 4 wk and urine collected for analysis. Lindane and metabolites were extracted and analyzed by HPLC followed by MALDI‐TOF characterization. HPLC spectrum of standard Lindane peaked at 6.0 min. and urine samples (n=6) peaked at 6.10–6.30 min. Control urine did not show any peak corresponding to Lindane (6.0–6.30 min). MALDI‐TOF analysis of standard Lindane showed a peak corresponding to 293 m/z whereas the urine samples showed major peaks at 292–293 m/z corresponding to Lindane along with minor peaks at 259, 269, 277, and 318 m/z corresponding to Lindane metabolites: ‐ chlorobenzene, ‐chlorophenol, ‐hexacholorohexane, and other derivatives. These results show that HPLC is sensitive for detecting Lindane and its metabolites and MALDI‐TOF can identify specific metabolites of Lindane in urine by matching spectrum peaks generated to the molecular weights of the metabolites. Thus, HPLC‐UV‐Vis‐MALDI‐TOF analysis can be a reliable, non‐invasive method of detecting lindane exposure and burden.

Supported by NHLBI (HL‐70669 and HL03674)
Nanoliposomes restore endothelial function of human adipose arterioles exposed to AL amyloidosis light chain proteins
Authors: Truran Seth , Weissig Volkmar , Franco Daniel A , Maltagliati Anthony , Burciu Camelia , Liu James , Migrino Raymond Q
Published: June 2021

AL amyloidosis light chain proteins (LC) induce endothelial dysfunction and tissue injury. Nanoliposomes (NL) are <100 nM phospholipid vesicles that could bind amyloid proteins. We tested whether NL can protect against LC induced endothelial dysfunction.

Methods

NL from cholesterol, sphingomyelin (1:1) and 5% phosphatidic acid were prepared by probe sonication. Subcutaneous adipose arterioles from patients without amyloidosis/vascular disease were cannulated. Baseline dilator response was measured (acetylcholine 10−9–10−4M and papaverine 10−4M, n=11). A second response followed 1 hour exposure to LC (20 μg/mL from AL patients’ urine, n=6) or LC+NL (1:1 mass, n=5). LC (20 μg) were also mixed with NL at 1:1, 1:5 and 1:10 mass ratios, centrifuged and the supernatant tested by Western blot using antibody to LC.

Results

LC caused impaired dilation to acetylcholine (10−4M: 49±6% vs. 89±4% control, p=0.003); the papaverine response was not different. NL restored dilator response to acetylcholine (10− 4M: 94±3%, p=NS vs. control, p<0.001 vs. LC). Western blot showed progressive reduction of soluble LC with increasing doses of NL suggesting physical sequestration by NL.

Conclusions

NL protected human adipose arterioles against LC induced endothelial dysfunction, possibly through sequestration of LC. This proof of concept finding supports exploring use of NL to treat AL amyloid tissue injury.
Striatin is a novel regulator of calcium homeostasis in cardiomyocytes
Authors: Abu-Zaid Ahmed , Inaya Aman , Farooqui Azhar , Ahmed Naser , Bakheet Dana , Dzimiri Nduna , Nader Moni
Published: June 2021

Striatin is a scaffold protein that associates with caveolin and calmodulin; key regulators of excitation‐contraction coupling in the heart. The aim of the present study was to probe for a potential role for striatin in regulating calcium homeostasis in cardiomyocytes. Our findings indicate that striatin is expressed in rat hearts (cardiomyocytes enriched fraction) with a higher expression level in neonates vs adults. Protein‐protein interaction assays revealed that, in the heart, striatin associates with calmodulin as well as caveolin‐1 and caveolin‐3 (muscle specific isoform). It was notable that the interaction between striatin and calmodulin was calcium sensitive: while calcium chloride (2 mM) showed robust pulldown of striatin with calmodulin, the calcium chelator EGTA (1 mM) attenuated this interaction. Moreover, KCl‐induced intracellular calcium [Ca2+]i increase was sustained in cardiomyocytes overexpressing striatin (adenoviral delivery) while [Ca2+]i returned to near basal levels in control cardiomyocytes (non‐target adenovirus). Collectively, our data indicate that striatin is expressed in cardiomyocytes and that it may play a role in maintaining [Ca2+]i homeostasis. This suggests that striatin may be involved in modulating cardiac excitation‐contraction coupling and emerges as a novel target for therapeutic strategies in cardiac diseases.
Application of implantable telemetry in swine heart failure models
Authors: Zhang Zhen-Du , Choy Suzana Jenny , Pitsillides Koullis , Sosa Margo , Kassab Ghassan
Published: June 2021

Swine animal models are commonly used to study the mechanism of heart failure (HF) and to develop new therapies. Continuous recordings of blood flow, ventricular and systemic blood pressures in awake, free‐roaming animals without the effects of anesthesia will provide valuable data on the progression and treatment of HF. The objective of this study was to evaluate simultaneous, totally implantable, telemetric measurements of these parameters in swine HF models. Solid‐state blood pressure catheters were placed in the right or left ventricle and descending aorta for pressure measurements while Doppler probes were placed around the LAD and branchocephalic arteries for blood flow velocity measurements. ECG electrodes were attached to the left ventricle. Each telemetry unit was implanted subcutaneously for up to 6 weeks into various HF models including A‐V fistula, aortic banding and high‐rate pacing. Sudden and chronic changes of hemodynamics were captured during the progression of HF. Systemic pressure progressively decreased within first 2 weeks in HF with pacing and recovered by 4 weeks; while the pressure increased progressively in HF with aortic banding for 4 weeks. The pressure did not significantly change within first 4 weeks, but LAD flow increased within 2 weeks in animals with A‐V fistula. The results showed that this biotelemetry system is capable of long‐term accurate monitoring of simultaneous blood flow, pressure and ECG. This system will have significant utility in chronic models of cardiovascular physiology and pathology.
Smooth Muscle Actin Polymerization and Vasoconstriction‐Induced Inward Remodeling of Resistance Arteries
Authors: Staiculescu Marius Catalin , Galinanes E. L. , Zhao G. , Li M. , Ulloa U. , Jin M. , Martinez-Lemus L.A.
Published: June 2021

In hypertension, the most common structural change in arterioles is inward eutrophic remodeling, a reduction in passive luminal diameter without variations in wall cross‐sectional area. As prolonged vasoconstriction causes inward eutrophic remodeling and is associated with vascular smooth muscle (VSM) actin polymerization, we hypothesize that prolonged exposure to norepinephrine (NE) + angiotensin II (Ang‐II) requires actin polymerization to induce inward remodeling. Actin‐Alexa 488 was electroporated into VSM within isolated rat‐cremaster arterioles. Exposure to NE+Ang‐II for 4 hours induced inward remodeling and reduced the fluorescence from actin‐Alexa by 42%. Cytochalasin D blunted the decreased fluorescence caused by NE+Ang‐II by 28%, and prevented the maintenance of vasoconstriction. In vitro, actin polymerization decreased the fluorescence of actin‐Alexa suggesting that in arterioles the NE+Ang‐II‐induced inward remodeling requires actin polymerization. Rho kinase inhibition also prevented NE+Ang‐II from maintaining vasoconstriction, while direct activation of Rho/Rac/Cdc42 resulted in inward remodeling. This suggests that actin polymerization mediated by Rho, Rac, and/or Cdc42 was needed for NE+Ang‐II to induce inward remodeling. These mechanisms may contribute to the structural narrowing of resistance vessels encountered in hypertension. Supported by NIH HL‐088105.
Improving Arterial‐Ventricular Coupling Reserve in Patients with Metabolic Disorders through Exercise Training
Authors: Fournier Sara B , Reger Brian , Donley David A , Bonner Daniel E , Warden Bradford E , Chantler Paul D
Published: June 2021

Metabolic disease is defined as a cluster of co‐morbidities, including hypertension, obesity, low high‐density lipoprotein cholesterol, high triglycerides, and high glucose. These risk factors are associated with cardiovascular mortality. People with metabolic diseases have functional limitations (reduced aerobic capacity). One determinant of functional capacity is arterial‐ventricular coupling (Ea/Ees), indexed as the ratio of arterial elastance (Ea;net arterial load) to left ventricular end‐systolic elastance (Ees;cardiac performance). We explored the relationship between the metabolic risk score (MRS) and the change in Ea/Ees, Ea, and Ees during exercise, before and after 8 weeks of training in 33 people. MRS was determined by adding the individual risk points for each metabolic risk factor noted above. At rest, Ea/Ees, Ea, and Ees were not related with MRS. In contrast, the change in Ea/Ees and Ees from rest to exercise was blunted with increasing MRS. 8 weeks of exercise training improved Ea/Ees due to an increase in Ees i.e., improved cardiac performance during exercise. No differences in the Ea/Ees or Ees during exercise were found in non‐trained individuals. The effects of training on Ea, Ees, and Ea/Ees were similar irrespective of the MRS. Exercise training represents a valuable treatment to improve cardiovascular function in metabolic disease patients. AHA11CRP7370056,5T32HL090610‐04.
Advanced Glycation End‐Products in Age‐Related Arterial Stiffening: Modulation by Sodium Nitrite
Authors: Eng Jason S , Sindler Amy L , Seals Douglas R , Fleenor Bradley S
Published: June 2021

Aging causes large elastic artery stiffening and this is associated with oxidative stress and increased advanced glycation end‐products (AGEs). We tested the hypothesis that vascular oxidative stress with aging induces AGEs, which increase intrinsic mechanical stiffness, and that sodium nitrite prevents this stiffening. Old (O, 27 mo, n=4) vs. young (Y, 6 mo, n=4) control male C57Bl/6N mice had greater (p<0.05) nitrotyrosine abundance (5.0 ± 1.1 vs. 1.0 ± 0.3 AU), a marker of oxidative stress, and AGEs (2.1 ± 0.2 vs.1.0 ± 0.1 AU) (p<0.05). Sodium nitrite treatment (50 mg/L in drinking water, 3 weeks) in O reduced (p<0.05) aortic nitrotyrosine (1.9 ± 0.6 AU) and AGEs (1.2 ± 0.2 AU). Stimulation of superoxide‐induced oxidative stress ex vivo with pyrogallol (10μM, 72 hr) in aortic segments from Y mice increased AGEs (2.3 ± 0.5 vs. 1.0 ± 0.1 AU, p<0.05), an effect prevented by treatment with sodium nitrite (1.1 ± 0.2 AU). Aortic rings from Y mice treated with AGEs (100μg/mL, 72 hrs) had a greater elastic modulus, a measure of mechanical stiffness, compared with control (3984 ± 236 vs. 2074 ± 218 KPa, p<0.05), and sodium nitrite prevented this effect (2148 ± 446 KPa). These results suggest that AGEs, induced by excessive superoxide‐associated oxidative stress, contributes to aortic stiffening with aging in mice. AGEs‐induced aortic stiffness may be preventable with sodium nitrite supplementation.
THE EFFECT OF OMEGA‐3 SUPPLEMENTATION IN HEARTS OF AGED RATS
Authors: Lennon-Edwards Shannon , Schellhardt Taylor , Kuczmarski James
Published: June 2021

Omega‐3 supplementation has been shown to be beneficial in reducing oxidative stress and inflammation. The purpose was to determine if 12 weeks of a high omega‐3 fatty acid diet would reduce age associated increases in myocardial oxidative stress and inflammation. 20 mature (M) (6 mo.) and 20 older (O) (15 mo.) SD rats were assigned to 2 diet groups: Control (CON) or Fish Oil (FO). Following the diet, animals were sacrificed and left ventricular heart tissue was harvested. Interleukin‐6 was significantly lower in MFO vs. OCON and OFO (26.58±0.67 vs. 37.77±3.85 & 37.68±2.23 pg/mg, respectively; p<0.05). Tumor necrosis factor‐alpha was not different among groups. Hydrogen peroxide production (H2O2) was reduced by FO treatment (p<0.01) but not significant in regards to age. However, OFO H2O2 trended towards significance vs. OCON (0.10±0.02 vs. 0.12±0.01 uM/mg ptn; p=0.09). A significant effect was seen for catalase with age (p<0.05), between MCON and OCON (3.04±0.38 vs. 4.49±0.36 U/mg ptn; p<0.05) and trended towards significance in OFO (3.04±0.38 vs. 4.25±0.36 U/mg ptn; p=0.1). There were no differences among groups for superoxide dismutase (p>0.05). These results suggest age‐associated increases in myocardial inflammation regardless of FO treatment. However, FO supplementation appears to increase some myocardial antioxidant activity and reduce H2O2.

Supported by UD Research Foundation Grant
Ethyl pyruvate protects against myocardial ischemia/reperfusion injury via mitochondrial membrane potential dependent and anti‐apoptotic mechanisms
Authors: Chun Byeong Jo , Moon Jeong Mi , Lee Byeong Guk
Published: June 2021

Purpose

A role Ethyl pyruvate (EP) in ischemia/reperfusion (I/R) injury is not clear. We investigated whether EP could inhibit cardiac myocyte apoptosis and reduce mitochondrial injury in the ischemic/reperfused heart of the mice.

Methods

Male C57BL/6 mice of 12–15 weeks of age were subjected to 25 min of ischemia followed by 45 min of reperfusion. A modified KH perfusion fluid was used, contained except where EP levels were varied. JC‐1 staining flow cytometry was used to examine mitochondrial membrane potential. We investigated mitochondrial structure, apoptosis rate and Bcl‐2, Bax, Caspase‐3 proteins. RT‐PCR was used to determine the expression of P38MAPK mRNA and JNK mRNA. Western blotting was used to measure the expression of P38MAPK, JNK and NFκB P65.

Results

Our results show that 4.0 mM EP group increased LVDP recovery rate and decreased mitochondrial ultrastructural damage as compared to other EP groups. The apoptosis rate and PCI of Bax, Caspase‐3 proteins in the 4.0 mM EP group were decreased, while the PCI of Bcl‐2 protein was increased. The expression of P38MAPK mRNA, JNK mRNA and protein of P38MAPK, JNK and NFκB P65 in free EP group was increased. The rate of loss Δψm cells in the 4.0 mM EP group was lower than in the other groups.

Conclusion

Our dates suggest that the EP plays an important role in protection of the myocardium against I/R injury and may represent a novel therapeutic target.
Testosterone induces skeletal muscle hypertrophy via Akt/mTOR/S6K1 pathway and the androgen receptor
Authors: Basualto-Alarcón Carla , Jorquera Gonzalo , Jaimovich Enrique , Estrada Manuel
Published: June 2021

The anabolic hormone testosterone is associated with muscle hypertrophy, but the intracellular mechanisms involved are poorly known. We studied whether signal transduction pathways and the androgen receptor are necessary to elicit hypertrophy in skeletal muscle myotubes. Testosterone induced an increase in myotube cross sectional area (control=134,5±10,2 μm2; testosterone=181,9±14,4 μm2) and in α‐actin protein levels at 12 hours. Morphological development of myotube sarcomerisation was more clearly established in testosterone stimulated myotubes at this time. Earlier times of testosterone stimulation showed increased transcription of α‐actin gene, concomitantly with no changes in atrogenes (MAFfbx and MuRF‐1) activity at 6 hours. Characteristic hypertrophy pathways were studied at short times: ERK1/2 and Akt showed an increase in phosphorylation status after testosterone at 5 and 15 minutes, respectively. S6K1 was phosphorilated at 60 minutes. This response was inhibited with LY294002, Akt‐inhibitor‐VIII and Rapamycin but not by PD98059. Similarly, the hypertrophic response at 12 hours was abolished with these inhibitors as well as partly by a siRNA against androgen receptor but not by PD98059. These results suggest interlink between pathways involving intracellular signal cascades and the classical genomic actions of androgens for testosterone‐induced skeletal muscle hypertrophy.

FONDECYT 1090276, FONDAP 15010006
From meat to bamboo: The role of the hypertrophied zygomaticomandibularis muscle in the giant panda (Ailuropoda melanoleuca)
Authors: Heller Aaron , Stock Stuart , Wright Barth
Published: June 2021

The giant panda (Ailuropoda melanoleuca) has evolved craniodental adapations for producing and withstanding high and repetitive bite forces incurred during bamboo feeding. One such adaptation are hypertrophied zygomaticomandibularis muscles (ZMs), which allow the giant panda to laterally shift the mandible and effectively comminute bamboo. We examined changes in biomechanical efficiency and bite force during chewing and biting in the giant panda using finite element analysis (FEA). A FE model was created of the giant panda cranium and mandible. We compared biting (greater ZM force on the loading side) and chewing (greater ZM force on the balancing side) muscle loads, with all other model conditions held constant. We found that the mandible is more efficient (able to generate higher bite forces at lower strains) when chewing than when biting at various bite points, but incurs higher peak von Mises stress when chewing. The opposite is true for the cranium, which is more efficient when biting than chewing. The ultimate shape of the adult cranium and upper face is influenced by the morphogenesis of various systems including the sensory organs and the brain, which may constrain the upper jaw. The mandible is under fewer constraints and has perhaps evolved to counteract the limitations in cranial efficiency when chewing bamboo.
Avian and Mammalian Skeletal Muscle Mitochondrial Enzyme and Electron Transport Chain Activities
Authors: Kuzmiak Sarah , Gardner Doree , Pangle Patrick , McInnis Haley , Willis Wayne T.
Published: June 2021

Birds are able to fuel flight, a moderate‐high intensity exercise, with fat, while mammals depend on carbohydrates for fuel at the same relative intensity. This difference in fuel selection persists in mitochondria (MITO) isolated from the skeletal muscle of these species, suggesting fuel selection can be controlled at the level of the MITO matrix. To compare the capacity rat and sparrow MITO to harvest electrons to the ability of the electron transport chain (ETC) to oxidize them, we assessed the activities of CAC and related enzymes, the Vmax of NADH oxidation from Complex I → IV, and cytochrome b content via myxothiazol titration. The Vmax of NADH oxidation (1074 ± 118 vs 516 ± 42 nmol O2·mg−1·min−1), as well as the cytochrome b content (1.50 vs 1.06 nmol·mg mitochondrial protein−1), were greater in sparrow compared to rat. These data suggests a greater capacity of sparrow ETC to oxidize electrons compared to the capacity of the dehydrogenases to produce them. This balance may result in a lower oxidation‐reduction potential in sparrow MITO, decreasing the inhibition of NADH on β‐oxidation and allowing fatty acid oxidation to proceed.

Rat
Sparrow

nmol·mg mito protein−1·min−1

Isocitrate Dehydrogenase (IDH)
276 ± 48
366 ± 51

Malate Dehydrogenase (MDH)
20600 ± 2628
22209 ± 2309

Citrate Synthase (CS)
2748 ± 258
4343 ± 600

Glutamate Dehydrogenase (GDH)
399 ± 51
51 ± 9

Aspartate Aminotransferase (AspAT)
5667 ± 233
19326 ± 1214
Secretory klotho interacts with parathyroid hormone (PTH) receptors
Authors: Takenaka Tsuneo , Inoue Tsutomu , Miyazaki Takashi , Suzuki Hiromichi
Published: June 2021

Background

We have previously demonstrated that chronic administration of secretory klotho into rats with adriamycin nephropathy retards renal injury and reduced vitamin D without changes in PTH levels (J Am Soc Nephrol. 2011; 22: 776A). Membrane‐type klotho acts as a receptor for FGF23. Klotho is expressed on cell membrane of parathyroid glands. Although FGF23 can act on parathyroid glands, direct effects of secretory klotho on PTH receptors have not been examined. Klotho is known to binds to receptors to WNT and TGF‐beta.

Methods

The interactions of secretory klotho and PTH receptors were examined under in vitro and in vivo conditions. Sepharose‐beads coated with protein G was mixed with antibody to PTH receptors in test tube. Then, PTH receptor was added to the tube, finally secretory klotho (10−8 to 10−11 M) was added. Tube was centrifugated, and supernant was discarded. Beads were washed three times with PBS. Residual proteins on the beads were detected. Under anesthesia, rats were treated with PTH (100 miicro‐g/Kg) in the presence and absence of secretory klotho (10 micro‐g/Kg). Urinary c‐AMP was measured.

Results

Klotho, PTH receptor, antibody to PTH receptor were found as the remaining proteins on the beads. Klotho was detectable at 10−9 M or more as the residual protein. Increases in urinary c‐AMP excretion by PTH were attenuated by the pretreatment with secretory klotho (3.0±0.5 vs 5.6±0.8 folds, p<0.05).

Conclusion

Secretory klotho binds to PTH receptors, inhibiting its signaling.
The Effects of FGF‐21 on Metabolic Regulation are Mediated by Changes in Plasma Ceramide Levels
Authors: Brozinick Joe Thomas , Wade Mark , Bui Hai-Hoang , Kuo Ming-Shang , Kharitinikov Alexei , Holland Will , Scherer Philip
Published: June 2021

FGF‐21, a unique member of the FGF family of growth factors has been shown to be a novel regulator of metabolism and energy utilization. However, the exact mechanism(s) whereby FGF‐21 mediates its effects have not been entirely elucidated. There is also considerable evidence that the insulin resistance associated with NIDDM is due to the accumulation of intracellular lipids in insulin responsive tissues (lipotoxicity), and in particular the sphingolipid ceramide has been implicated in this process. Here we have examined FGF‐21's ability to mediate plasma ceramide levels in an attempt to clarify the mechanism of action of this novel hormone. Analysis of plasma ceramide levels in FGF‐21 TG mice showed a marked reduction in ceramide levels in parallel with increased insulin sensitivity. Chronic dosing of a FGF‐21 analog in DIO mice showed significant changes in several ceramide species, with the longer chain ceramides being most affected. Adiponectin has previously been shown to have a role in regulation of plasma ceramide through the ceramidase activity of its receptor. Examination of plasma adiponectin levels from DIO animals dosed with an FGF‐21 analog showed that plasma adiponectin increased in parallel with a reduction in plasma ceramides. Further, injection of FGF‐21 into adiponectin knock‐out mice had a reduced effect on plasma ceramide levels in conjunction with impaired effects on body weight reduction and blood glucose. Together these data indicate that at least a portion of FGF‐21's improvement of metabolic homeostasis in insulin resistance may be due to its effects on ceramide levels.
Vagal control of heart rate is increased during post‐exercise recovery
Authors: White Daniel Wade , Carlton Joshua , Kay Victoria , Eubank Wendy , Raven Peter B
Published: June 2021

Increases in exercise intensity are known to reset, in an upward and rightward direction, the arterial baroreflex (ABR) control of heart rate (HR) and mean arterial pressure (MAP). ABR function during recovery from exercise has not been extensively studied and therefore is unreported in the literature. We hypothesized that carotid baroreflex (CBR) function curves would recover with a trend opposite to the original intensity related resetting following exercise. To test this hypothesis, healthy young subjects performed cycling exercise at two workloads to establish HRs of 120 and 150 bpm. CBR function curves were collected using the neck pressure/neck suction technique. An increase in HR during recovery vs. rest (p=0.032) was recorded in all subjects without a change in MAP. From rest to recovery there were significant increases in the response range (RR) of HR (p=0.029) and the sensitivity or gain of the ABR function curves (p=0.036). The increase in HR without an increase in MAP was expected, but the RR increase during recovery due to an increase in threshold without a concomitant increase in saturation point was not. It is concluded that vagal control of HR during recovery from exercise is increased without a change in the CBR control of blood pressure.

Supported by a TACSM SRDA.
Interaction of thiazolidinediones with renal organic cation transporters
Authors: Soodvilai Sirima , Soodvilai Sunhapas
Published: June 2021

We determined the interaction of TZDs on organic cation transporters (OCTs) in Chinese hamster ovary (CHO‐K1) cells stably transfected with rabbit (rb)OCT1 and rbOCT2, and in murine isolated renal cortical slices. Rosiglitazone but not pioglitazone inhibited uptake of 3H‐MPP+, a substrate of rbOCT1 and rbOCT2, via both transporters with half maximal inhibitory concentration (IC50) of rosiglitazone for rbOCT1‐ and rbOCT2‐ mediated MPP+ uptake of 7.4 μM and 2.5 μM, respectively. The mode of rosiglitazone inhibition was further determined using kinetic analysis. We showed that rosiglitazone decreased the maximal transport (Jmax) but without effect on the transporter affinity (Kt) indicating the inhibitory effect of rosiglitazone on rbOCT1 and rbOCT2 was noncompetitive manner. Similar to the effect seen in the cell‐cultured system, the inhibitory effect of rosiglitazone was also observed in intact renal cortical slices. Taken together, we concluded that rosiglitazone seemed to inhibit transport activity of OCT1 and OCT2 by interfering with non‐substrate‐ binding site of the transporters.
Absence of reproductive organs increases somatic maintenance in the Hawk moth (Manduca sexta): A direct test of the disposable soma hypothesis
Authors: Ojha Jaika , Davidowitz Goggy
Published: June 2021

Flight and reproduction are major resource sinks in flying organisms. The disposable soma hypothesis predicts that reducing reproduction allows more nutrients to be allocated for maintenance of somatic tissues, such as flight muscles. We tested this hypothesis by comparing the flight muscle structures of oophorectomized (ovaries removed) and orchiectomized (testes removed) individuals at different ages in Manduca sexta. Overall, oophorectomized and orchiectomized individuals have significantly greater number of mitochondria and percentage of area occupied by mitochondria compared to sham‐operated individuals. In addition, oophorectomized and orchiectomized individuals have significantly longer sarcomeres and larger size myofibrils compared to sham‐operated individuals. At day 7, oophorectomized and orchiectomized individuals exhibited smaller size mitochondria compared to sham‐operated individuals, suggesting a delay in mitochondrial degeneration. The levels of glycogen granules at different ages were also higher in oophorectomized and orchiectomized individuals compared to sham‐ operated individuals. These findings directly suggest that in the absence of reproductive organs, the increase in available energy is utilized for the maintenance of flight muscles, hence supporting the disposable soma hypothesis.