bluuebunny/crossref_metadata_2025_split huggingface dataset:
High sodium intake interacts with ADD1 Gly460Trp polymorphism in increasing hypertension odds among Filipino women
Authors: Lee Nanette R , Borja Judith , Duazo Paulita , Mohlke Karen , Adair Linda S 
Published: June 2021

Hypertension (HTN) is a multifactorial disease influenced by environmental and genetic factors. We examined the association between high sodium (Na) intake and HTN among 1747 unrelated Filipino women (ages 35‐69 yr) and assessed whether the association is modified by a gene polymorphism (Gly460Trp of alpha adducin (ADD1)) shown to increase Na re‐absorption in the kidney. We used data gathered by the Cebu Longitudinal Health and Nutrition Survey in 2005 and defined high Na intake as: at least 4600 mg/day (200% of recommended upper limit). Mean Na consumption was 2900 mg/day, 15% were categorized as high intake, and 29% were hypertensive. Adjusting for age, BMI, overweight duration and other confounders, logistic regression analyses showed that high Na intake increased HTN odds, especially among women homozygous for the 460Trp allele (19%). Women with lower Na intake carrying one or more copies of the 460Gly allele (reference) had the lowest odds of HTN: odds ratio (OR, 95% CI) for women with high Na intake carrying the 460Gly allele was 1.2 (0.8, 1.6) while that for women with high Na intake and homozygous for 460Trp was 2.9 (1.4, 6.0). The association among Na intake, ADD1 Gly460Trp, and hypertension was further modified by overweight duration. With relatively high frequency of the 460Trp allele compared to Caucasians, efforts to reduce Na intake should be strengthened.1R03TW008133‐01, 1 R01 HL085144‐01, R01 DK078150
Maternal HIV status and motor milestone acquisition among Ghanaian infants
Authors: Lartey Anna , Marquis Grace S , Perez‐Escamilla Rafael , Mazur Robert , Sellen Daniel 
Published: June 2021

As part of the RIING project (Research to Improve Infant Nutrition and Growth) we examined infants' motor milestone (MM) acquisition in relation to Ghanaian mothers' HIV status. Mothers' prenatally diagnosed as HIV positive (n=104), HIV negative (n=132) and HIV status unknown (n=129) were followed up twice weekly at home for MM assessment from 4 to 12 months. At each home visit the following were assessed: i) sitting without support, ii) hands and knees crawling, iii) standing with assistance, iv) walking with assistance, v) standing alone, and vi) walking alone. The mean age (days) for MM achievement was not significantly different among children of the three groups of mothers (all groups combined: sitting without support 170.7± 24.5 d, hands and knees crawling 243.0± 34.9 d, standing with assistance 261.0± 38.9 d, walking with assistance 295.3± 46.8 d, standing alone 329.0± 36.7 d, and walking alone 350.3± 35.1 d) However, by 12 months 15.4 % of the HIV positive, 31.8% of the HIV negative, and 10.1% of the HIV unknown mothers' children were walking alone (p<0.05). The results suggest possible influence of maternal HIV status on child MM acquisition.Funded by NIH Grant HD436020
Metabolic Syndrome in HIV+ Asymptomatic Adults in Botswana, Africa
Authors: Sales Sabrina , Campa Adriana , Makhema Joe , Dusara Priti , Tsalaile Lesedi , Burns Patricia J , Baum Marianna K , Marlink Richard 
Published: June 2021

ObjectiveTo determine the prevalence of metabolic syndrome (MS) in a cohort of asymptomatic and antiretrovirally naïve HIV+ adults in Botswana, and its association with other risk factors for cardiovascular disease (CVD).MethodsAfter consenting, socio‐demographic and medical questionnaires were completed, blood pressure and anthropometries taken. Fasting blood was drawn for total blood cholesterol, HDL cholesterol, triglycerides, and glucose. MS was defined according to NCEP ATP III guidelines.ResultsOf the 402 participants, 69.4% were female and the mean age was 33.7±8.1 years. The prevalence of MS in this cohort was 7.7% (n=31), 32.8% were overweight (BMI >25 kg/m2), 11.6% were obese (BMI >30 kg/m2), 21.9% had hypertenstion, 31.9% reported alcohol use and 19.5% tobacco use. Only 5.1% had high cholesterol and 14.3% high LDL levels. Risk factors significantly associated with MS were age (OR=1.10, 95% CI: 1.04, 1.16, p<0.01) and BMI (OR=1.26, 95% CI: 1.16, 1.36, p<0.01) after adjusting for age and gender.ConclusionsThe prevalence of MS in this cohort is similar to other sub‐Saharan African HIV+ cohorts, but low compared to that in developed countries. Preventive interventions should be implemented to reduce the future impact of MS on HIV‐related CVD risk, especially when these patients start their antiretroviral treatment.Funded by NIDA
Contribution of tea to iron status in a rural female population
Authors: Osowski Jane Marie , Specker Bonny 
Published: June 2021

ObjectiveTo investigate the association between tea consumption and iron status in a rural South Dakota female population.MethodsThe study design was cross‐sectional. This study examined whether there is a correlation between tea consumption and iron status. A convenience sample of 136 adolescent girls and women living on Hutterite colonies in rural South Dakota participated in the study. The main outcome measures included hemoglobin (Hgb), expressed as mg/dL, the amount of tea consumed, expressed in cups/meal and the amount of dietary iron consumed, expressed as mg/day. The sample was divided into two groups depending on if they consumed tea at mealtime or did not consume tea at mealtime. Differences between group means were tested using Students t test and chi‐square analysis. Multiple regression was used to assess the relationship between Hgb levels and tea consumption controlling for variables with relevance to the main outcome measure.ResultsThe difference in mean Hgb concentrations between groups did not differ. The mean intake of tea at mealtime was 2 ± 1 cups. The amount of black tea consumed at mealtime was significantly more than herbal or green tea (p = 0.05). The difference in the amount of iron consumed per day between groups was not significant (p = .11). No relationship was found between hemoglobin and amount of tea consumed while controlling for variables that influence hemoglobin.ConclusionsIn a seemingly healthy rural female population consuming tea in the amounts that were observed with a whole meal does not have an effect on hemoglobin levels.
A panel of biomarkers for esophageal squamous cell carcinoma
Authors: Kashyap Manoj K , Marimuthu Arivusudar , Kishore C. J. H. , Peri Suraj , Ranganathan Prathibha , Sanjeeviah Ravinder C. , Mahmood Riaz , Kumar K. V. Veerendra , Vijayakumar M. , Montgomery Elizabeth , Kumar Rekha V. , Pandey Akhilesh 
Published: June 2021

We have carried out mRNA profiling of 20 esophageal squamous cell carcinoma (ESCC) using whole genome DNA microarrays for identification of novel biomarkers. We chose several novel candidates including periostin (POSTN), lumican (LUM), four and a half LIM domains 1 (FHL1), collagen triple helix repeat containing 1 (CTHRC1) and PTRF interacting protein alpha 1 (PPFIA1) to carry out immunohistochemistry‐based validation on a larger sample set using tissue microarrays. Overexpression of periostin was observed in 139/140 (99%) of cases while. lumican was overexpressed in 141/141(100%) of cases and expression of FHL1 was found to be decreased in 132/145 (91%) of cases. These markers could be further tested in sera of patients as candidates for early detection of this cancer.This work was supported by an Independent Senior Research Fellowship to MKK from the Indian Council of Medical Research, New Delhi, India.
Upregulation Of Cardiac NOS Due To Endotoxemia And Vagal Overactivity Contributes To The Hypotensive Effect Of Chronic Ethanol In Female Rats
Authors: El‐Mas Mahmoud M , Fan Ming , Abdel‐Rahman Abdel A 
Published: June 2021

We have previously shown that chronic ethanol causes sustained hypotension in female rats. Here, we investigated: (i) roles of cardiac contractility and autonomic activity in ethanol‐induced hypotension, and (ii) whether endotoxemia‐induced upregulation of cardiac NOS underlies hemodynamic effects of ethanol. Telemetric monitoring of blood pressure (BP), heart rate (HR), and +dP/dtmax (index of myocardial contractility) was performed in female rats receiving liquid diet with or without ethanol (5% w/v, 13 weeks). Cardiovascular autonomic control was assessed by frequency analysis of interbeat intervals (IBI) and systolic BP (SBP). Compared with control rats, ethanol caused sustained reductions in dP/dtmax and BP. Spectral analysis of IBI revealed increases in high‐frequency band (IBIHF, 0.75‐3 Hz) and decreases in IBILF/HF ratio in ethanol‐fed rats, suggesting increased cardiac parasympathetic dominance. Vascular sympathetic tone was not affected by ethanol because SBP spectral bands and plasma norepinephrine remained unchanged. Myocardial iNOS and eNOS, but not nNOS, expressions and plasma endotoxin and nitrite/nitrate were increased by ethanol.Conclusionupregulation of cardiac iNOS and eNOS, due to endotoxemia and/or vagal overactivity, might account for reductions in dP/dtmax and hypotension caused by chronic ethanol in female rats.Supported by Grant R01 AA014441 from NIAAA.
The Effects of Acute Phase Proteins in the Blood‐brain Barrier and Tight Junction Proteins
Authors: Zhang Shuangling , Mark Karen S. 
Published: June 2021

Tight junction (TJ) proteins, which form cell‐to‐cell contacts, play a central role in maintaining the integrity of the blood‐brain barrier (BBB) and brain homeostasis. Acute phase proteins (APP) are elevated in chronic inflammatory diseases but their effects in BBB function and structure have not been investigated.The objective of this study was to examine the effects of APPs on an in vitro BBB model using rat brain microvessel endothelial cells (RBMEC). Following treatment with APPs, culture supernatant and protein were collected. The following methods were used in our study: enzyme‐linked immunoabsorbant assay (ELISA) to measure cytokines, Western blot analysis for TJ protein expression, and immunohistochemistry for TJ protein localization. Additionally, RBMEC permeability following APP treatment was measured.Results from this study showed a significant increase of TNF‐α in the supernatant following treatment with α‐1‐acid glycoprotein (AGP). Increased permeability was seen with AGP treatment while serum amyloid A treatment induced decreased permeability. Our immunohistochemistry results showed a decrease in claudin‐5 expression following haptoglobin treatment.In summary, our results show that APPs have direct effects on BBB function and TJ protein localization. This suggests that APPs may play a role in altering BBB integrity in chronic inflammatory diseases.Funded by: NHLBI, R15‐HL092561
Cytoprotective effect of a synthetic triterpenoid against oxidative stress in human umbilical vein endothelial cells (HUVEC)
Authors: Wang Xinyu Eric , Stavchansky Salomon , Bowman Phillip 
Published: June 2021

Induction of phase II enzymes, in particular the 32 kd stress protein heme oxygenase‐1 (HO‐1), is cytoprotective in human endothelial cells. We previously demonstrated that caffeic acid phenethyl ester (CAPE) was cytoprotective against menadione‐induced oxidative stress in HUVEC largely via the induction of HO‐1.* Here, we tested the cytoprotective activity of 1[2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oyl]imidazole (CDDO‐Im), a new synthetic triterpenoid (Dr. Michael Sporn, Dartmouth University) against oxidative stress. Dose response studies indicated that CDDO‐Im at 100 nM was more cytoprotective against menadione toxicity than an optimal dose of CAPE (20 µM), resulting in endothelial cell survival of 80% compared to 60% for CAPE. Messenger RNA for HO‐1 was increased 90‐fold in the presence of CDDO‐Im, while only 13‐fold by CAPE. Western blot analysis of HO‐1 protein product indicated that by 6 h, CDDO‐Im induced an 8‐fold higher level of HO‐1 while CAPE induced a 2‐fold increase. The results indicate that CDDO‐Im is a much more potent cytoprotectant than CAPE, and this beneficial effect correlates well with the induction of HO‐1.*Wang X, et al. Eur J Pharmacol. 2008 Sep 4;591(1‐3):28‐35.
Inhibition of hypothermic preservation‐induced Smac/DIABLO protein expression by diazoxide in donor rat myocardium
Authors: JIANG Jian‐ping , ZHU Li , CHEN Ying‐ying , SHEN Yue‐liang 
Published: June 2021

AIMTo investigate the effect of a mitochondrial ATP‐sensitive potassium channel (mitoKATP) opener diazoxide (DE) on Smac/DIABLO protein expressions in rat heart suffered from different duration of hypothermic preservation.METHODSThe Langendorff model of isolated rat heart was used. After stored in 4ºC Celsior solution with or without DE (30 μmol/L) for different time (0, 3, 6, 9 or 12 h). Cell apoptosis was detected by TUNEL technique. The expression of Smac/ DIABLO protein was also analyzed by Western blotting.RESULTS(1) Compared with the hypothermic preservation groups, DE reduced the percentage of apoptotic cells. (2) The peak level of Smac/DIABLO protein expression appeared at 6 h after hypothermic preservation, which was postponed to 9 h by DE. (3) The above effects of DE were attenuated by a mitoKATP channel inhibitor 5‐hydroxydecanoate (5‐HD).CONCLUSIONSThe findings indicate that in the isolated rat heart DE protects myocardium against different duration of hypothermic preservation injury via opening of mitoKATP channel and inhibition of Smac/DIABLO protein expression.
β3‐Adrenergic receptor gene polymorphisms and lower urinary tract function
Authors: Michel Martin C , Teitsma Christine A , Vrydag Wim , Baas Frank , de la Rosette Jean JMCH 
Published: June 2021

The β3‐adrenergic receptor (β3AR) plays an important role in urinary bladder relaxation, and the human β3AR gene is polymorphic. Its Trp64Arg single nucleotide polymorphism (SNP) is potentially associated with disease states such as obesity and type 2 diabetes. Therefore, we have explored whether this SNP is associated with an altered bladder function in vivo. DNA was obtained from 1015 men with voiding dysfunction who had undergone full urodynamic phenotyping prior to treatment, and genotyping was performed by MALDI‐TOF. 131 (12.9%) and 6 subjects (0.6%) were heterozygous and homozygous, respectively, for the Arg64 allele, confirming prevalence data in other Caucasian populations. However, there was no association of this allele with any lower urinary tract function parameter including cystometric measurements and symptom scales. Most importantly, bladder compliance, which is under direct control of the β3AR, varied over a wide range within the group but was not associated with genotype. We conclude that the Trp64Arg SNP does not affect baseline urinary bladder function in vivo.Source of fundingAstellas Europe, EU FP 7 program
Epidermal growth factor induces lysophosphatidic acid type 1 receptor regulation through phosphorylation
Authors: Santana Christian Colin , Vásquez Erendira Avendaño , Sáinz Adolfo García 
Published: June 2021

Lysophosphatidic acid (LPA) is a local hormone/autacoid/ growth factor involved in many cellular responses such as: cell migration, proliferation and surviving, platelet aggregation, smooth muscle contraction, neurotransmitter release, establishment of focal adhesions, neurite retraction and cell rounding (among many others). The actions of LPA are mediated through a family of G protein coupled receptors (GPCRs) that includes five subtypes LPA1‐5 receptors which can couple to different G proteins. Phosphorylation of GPCRs is one of the earliest events that regulate their function. Current evidence indicates that homologous desensitization of these receptors mainly involves G protein‐coupled receptor kinases (GRKs), whereas in heterologous desensitization second messenger‐activated kinases play a key role. The primary goal of this work was to study the possibly regulation of LPA1 receptor induced by EGF receptor activation. The LPA1 receptor, tagged with the green fluorescent protein, was transfected into C9 cells. Stimulation with LPA induces an increase in intracellular calcium concentration, LPA1 receptor phosphorylation and internalization. Activation of EGF receptors decreases (50%) LPA‐induced intracellular calcium increase. In addition, EGF receptor activation also induced LPA1 receptor phosphorylation and internalization. This "crosstalk" seems to involve protein kinase C, since pharmacological inhibitors markedly decreased EGF‐induced LPA1 receptor phosphorylation.This research was partially supported by Grants from DGAPA (IN206302) and CONACyT (079908).
Common human alpha2a&c adrenergic receptor polymorphisms do not affect cellular processing nor surface trafficking
Authors: Angelotti Timothy , Sorensen Matt , Hurt Carl 
Published: June 2021

Naturally occurring variant genetic forms of α2a and/or α2c adrenergic receptors (α2a&c ARs) have been identified and linked to congestive heart failure. Two well described α2a&c AR variants occur within the 3rd intracellular loop, α2aLys251 and α2cDel322‐325. We investigated if these variant forms exhibited alterations in localization or cellular processing to account for their phenotypic differences.Human cDNA encoding wild‐type and polymorphic α2a&c ARs were either purchased commercially or created using standard Quick Change mutagenesis techniques, incorporating an amino terminal HA epitope. Each construct was examined with respect to drug binding, biochemical processing (e.g. glycosylation), and surface and total expression (e.g. immunocytochemistry and FACS analysis).All four cDNA constructs were successfully transfected and expressed in HEK293 cells. RX 821002 binding did not differ greatly between wild‐type and polymorphic forms. Transfected cells were analyzed by immunocytochemistry and FACS; neither polymorphic form demonstrated differences in cell surface or intracellular expression patterns. Lastly, endoglycosidase digestions of transfected cell membranes revealed that the polymorphic forms were processed in a similar manner as their wild‐type counterparts.It has been shown previously that certain GPCR polymorphisms can affect receptor stability and trafficking. We examined the two most common α2a&c AR polymorphisms and found no discernable difference in receptor expression, drug binding, surface trafficking, or biochemical processing. Therefore, phenotypic differences between wild‐type and polymorphic forms are most likely due to signal transduction, or possibly neuronal specific influences.This work was supported in part by NINDS K08 NS050654‐01A1 (TA)
A model study of vascular microbubble transport in pulsatile blood flow through bifurcating vessels
Authors: Valassis Doug T. , Dodde Robert E. , Eshpuniyani Brijesh , Fowlkes J. Brian , Bull Joseph L. 
Published: June 2021

The behavior of long gas bubbles suspended in liquid flowing through bifurcating vessel network was investigated experimentally and theoretically as a model of vascular bubble transport. This work is motivated by a developmental gas embolotherapy in which perflurocarbon microbubbles are selectively formed in vivo and subsequently lodge to occlude blood flow to tumors. The bubbles originate from encapsulated liquid droplets that are small enough to pass through capillaries, allowing intravenous injection. The homogeneity of tumor necrosis depends on the transport and lodging of emboli. A bench top experimental model was used to explore the effects of flow pulsatility, heart rate, gravity, and bifurcation roll angle on bubble splitting and lodging. A corresponding time‐dependent one‐dimensional theoretical model was also developed. At a bifurcation roll angle of 45‐degrees, the most distinct difference in splitting ratios between three physiologic frequencies (1, 1.5, 2 Hz) was observed. As roll angle increased, lodged bubble volume in the first generation channel increased while bubble volume beyond the second bifurcation proportionately decreased. The results elucidate the effects of pulsatile flow and suggest the potential of gas embolotherapy to occlude blood flow to tumors. These finding are also relevant to air embolism.This work was supported by NIH grant R01EB006476.
Reduction in endothelial glycocalyx thickness after hemorrhage
Authors: Torres Filho Ivo P , Vink Hans , Torres Luciana , Pittman Roland 
Published: June 2021

Although some evidence suggests that ischemia induces changes in the endothelial glycocalyx (EG), little information is available about the EG following hemorrhagic hypotension (HH). We have employed video analysis to obtain preliminary data on EG changes following hemorrhage. Using intravital videomicroscopy, we studied the spinotrapezius muscle of anesthetized rats subjected to HH (40% blood vol.) for over 1 h. The analog video camera signal was digitized using standard software to DV‐AVI format. About 100 frames of several video clips (3‐5 s each) were processed using specially designed software to derive dimensions of the endothelial glycocalyx from the gap between erythrocytes and the luminal endothelial surface. Frequency distributions of the EG thickness during baseline and during HH showed a shift to lower values following hemorrhage, corresponding to a reduction in EG thickness of nearly 50 % (1.1 µm [range: 0.4 ‐ 4.3 µm] vs 0.6 µm [range: 0.3 ‐ 1.3 µm]). These changes occurred despite similar distributions of anatomic diameters (baseline range: 9 ‐ 24 µm; HH: 10 ‐ 21 µm). The findings suggest that the analysis of EG changes using in vivo video recordings can be used to investigate changes following HH and provide preliminary support for our hypothesis that these low flow states cause reductions in the endothelial surface layer thickness.SupportNIH, NWO, NHS, (HV: NHF grant 2005T037).
Integrating Microvascular, Interstitial, and Lymphatic Function with a Balance Point Characterization of Interstitial Fluid Volume and Protein Regulation
Authors: Dongaonkar Ranjeet M , Laine Glen A , Stewart Randolph H , Quick Christopher M 
Published: June 2021

ObjectiveTo develop simple algebraic formulas and an intuitive graphical approach to characterize interstitial fluid volume and protein regulation, and to derive insights that are not available from conventional numerical approaches that are overly complex, conceptually opaque, and lack generality.MethodsEight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for interstitial fluid pressure and protein concentration as functions of parameters characterizing microvascular, interstitial and lymphatic function. Model results were validated by comparing to reported experimental values.ResultsEquilibrium values of interstitial fluid pressure and protein concentration arise as balance points from the graphical intersection of transmicrovascular flux and lymph flow (analogous to Guyton's classical cardiac output‐venous return curves). Algebraic solutions reveal that interstitial fluid pressure and protein concentration result from a ratio of the microvascular filtration coefficient and the effective lymphatic resistance, and are independent of interstitial compliance. Model results are consistent with reported measurements.ConclusionThe present work presents a simple, transparent, and general balance point approach to predict lymph flow, interstitial fluid pressure and protein concentration that yields new insights concerning the complex interaction of microvascular, interstitial and lymphatic function. Supported by NIH‐K25HL070608 (CMQ), AHA‐0565116Y (CMQ), AHA‐0365127Y (RHS), CDC‐623086 (GAL).