bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio‐demographic and geographic variation of overweight and obesity in Uganda
Authors: Christoph Mary J , Turi Kedir N , Grigsby‐Toussaint Diana S
Published: June 2021

Overweight, obesity, and related chronic diseases are understudied in sub‐Saharan Africa, and even fewer studies have observed geographic correlates, necessitating an investigation of geospatial population patterns. We used ArcGIS 10.1 to investigate clustering of overweight and obesity in rural and urban areas of Uganda for 2,420 adult females and children, based on aggregated latitude and longitude data from the 2011 Uganda Demographic and Health Survey (DHS). We further examined socioeconomic factors in STATA 10.0 to show spatial heterogeneity of overweight and obesity. Overweight and obesity clustered in larger cities, and were significantly correlated with high education level and wealth index; further, 52.9% of overweight women lived in urban areas, compared to just 26.8% of normal‐weight females. Overweight or obese women were also more likely to have overweight children (21.8%) than their normal or under‐weight counterparts (16.6%). Our results suggest that there is a significant burden of chronic disease in Uganda, particularly in the capital and in wealthier regions of the country. This study underscores the necessity of using geostatistical tools to elucidate the etiology of overweight, obesity, and the increasing rates of chronic disease in Sub‐Saharan Africa. This research was supported by the UIUC Illinois Transdisciplinary Obesity Prevention Program.

Grant Funding Source: Illinois Transdisciplinary Obesity Prevention Program
Reverse translational research with a neuroanatomic focus: From the bedside to the bench.
Authors: Tubbs R. Shane
Published: June 2021

Translational research continues to be an underinvestigated area of science. One discipline that has had scant attention by those who practice translational research is neuroanatomy. As a clinician and neuroanatomist, the author has experienced success with a reverse translational research model. This paradigm identifies surgical problems and in the anatomy laboratory, investigates ways of answering these issues. The goal of such research is to improve patient outcomes in an expedited manner. The author reviews his 20 year experience with identifying common neurosurgical issues and addressing them with neuroanatomical investigation.
The pedagogy of technology: Attitudes of biochemistry students towards practice questions in online game or pdf format
Authors: Milner Rachel Elizabeth , Wright Adrienne , Parrish Jonathan , Keenan Louann , Gnarpe Judy
Published: June 2021

In our biochemistry course we provide multiple choice questions in PDF format. Recently, we decided to use an online game. To explore possible advantages of this approach, we compared students’ attitudes towards questions in online game or PDF format. Students had access to either the PDF or the online game. Feedback was collected using a survey and analyzed by item analysis. Open‐ended comments were also solicited. The comments were grouped as either positive or negative and then categorized. The number and nature of the comments in each category was compared for the two groups. Item analysis showed that the questions were perceived as equally valuable by both groups. However, the comments revealed notable differences in attitude. The game‐users submitted a greater proportion of negative comments (71%) than PDF users (39%). The negative comments revealed that game users complained more frequently about technical difficulties, and PDF users complained more frequently about question content and errors. The positive comments revealed that both groups felt the questions helped them in exams. However, only game users reported that the format was ‘engaging and fun.’ Overall, our students valued the questions provided, regardless of format. However, those using the game and PDF formats reported quite different negative and positive attitudes, which likely impact the function of the practice questions as a learning tool.
Using imaging biomarkers in the histological validation of Alzheimer's disease
Authors: Hansen Megan Salin , Salin Ashley , Barzee Brigham , Stone Megan , Bridgewater James , Kavafyan Talar , Steed Kevin , Stark Elena , Dong Hongwei , Toga Arthur W. , Vinters Harry V. , Wisco Jonathan J.
Published: June 2021

Without a cure for Alzheimer's disease (AD), early diagnosis and reliable prognosis through validation of biomarkers is critical in preventing irreversible brain damage and abnormal changes in the brain. Iron is readily visible in T2* MRI, and has been shown to be spatially correlated with amyloid beta (Aβ) plaques. Neurofibrillary tangles of tau protein are also associated with AD. We examined the spatial relationship between tau, Aβ, and iron accumulations in the entorhinal cortex of 3 serial sections in 2 subjects. This area is the first, and eventually one of the most heavily damaged neocortical area in AD, and thus would be an excellent area of the brain to visualize anatomic changes in early stages of the disease. Using OlyVIA software and Photoshop, we superimposed and registered all 3 sections with their corresponding stains for comparison and visualization of how the markers are localized in space. Our findings show correlations between both tau and Aβ depositions with Fe accumulations. Established patterns of similarity between Aβ, tau, and/or iron will serve as biomarkers on an MRI, permitting earlier predictions concerning the onset of AD.

Grant Funding Source: NIH/NIA 1 R21 AG037843‐02, NIH/NCRR P41 RR013642‐12S1, Translational Research Fund (UCLA), and the McGinty Family Foundation
Interplay of DNA polymerase lambda, Protection of Telomeres (Pot) 1 and TERRA in telomere elongation
Authors: Maga Giovanni , Lingner Joachim , Hübscher Ulrich
Published: June 2021

About 10% – 15% of cancer cell types do not express telomerase, but they use the Alternative Lengthening of Telomeres (ALT) pathway, to counteract telomere shortening. The molecular details of the ALT reaction are poorly characterized and the DNA polymerase (pol) involved in the synthesis step is not known. Here, we show that human DNA pol lambda can actively and efficiently promote annealing telomeric repeats to the complementary C‐rich strand and use it to prime DNA synthesis. DNA pol lambda is associated to telomeres of cells in vivo. Replication protein A negatively regulates this activity, but its inhibition can be counteracted by the Rad9/Hus1/Rad1 complex and the Protection of Telomeres protein 1, which physically interact with and stimulate DNA pol lambda. We show that the telomeric non‐coding RNAs, TERRA can compete with telomeric DNA for annealing and elongation by DNA pol lambda and that Pot1 can counteract this effect. We propose that R‐loops formed by TERRA RNAs at telomeres can function as entry point for the strand invasion during ALT, in a recombination‐independent mechanism. In addition, DNA pol lambda may help to bypass TERRA R‐loops during telomere DNA replication. Supported by an Italian Cancer Research Association AIRC grant.
In vitro evaluation of arylic derivatives as free radicals scavengers and myeloperoxidase inhibitors
Authors: Alemán Diana , Hernández Martha Cecilia Rosales , Basurto José Correa , Durán Araceli Ramírez , Wejebe Jessica Elena Mendieta
Published: June 2021

Several pathological conditions have been associated with an oxidative stress state, due to several enzymatic systems such as peroxidation and chlorination of myeloperoxidase (MPO). Oxidative stress is defined as the loss of homeostasis by the increased amount of free radicals production and the amount of endogenous antioxidants, which, as consequence, generate systemic complications such as micro and macrovascular angiopathies. It has been shown that several exogenous compounds are able to counteract the noxious effects of free radicals, that's why the main aim of this study is to evaluate in vitro the antioxidant capacity of a family of 6 derivatives, using as a pattern drug 5‐aminosalycilic acid (5‐ASA).

The antioxidant capacity of the proposed compounds, such as the witness drug 5‐ASA, where tested by the assay of the radical cation 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid (ABTS), the ferric reducing ability of plasma (FRAP) assay, and the discoloration of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay.

Inhibition of peroxidation of MPO was tested by the O‐dianisidine assay, using 4‐aminobenzoic hydrazide (4‐ABAH) as witness compound, and 5‐ASA as the pattern.

Results so far show that the proposed compounds have antioxidant activity, so as they were able to inhibit peroxidation of MPO in a higher percentage than the witness drug and the pattern.
An increase in bile acids in enterohepatic circulation within a physiological range induces some pathologic features in metabolic syndrome
Authors: Yoshitsugu Reika , Kikuchi Keidai , Hagio Masato , Shimizu Hidehisa , Hara Hiroshi , Ishizuka Satoshi
Published: June 2021

Metabolic syndrome (MS) caused by western diet raises a risk of life‐threatening disorders. Ingestion of excess fat with sucrose induces secretion of bile acids (BAs), which fundamentally contributes to lipid absorption in intestine. Such increase in BAs might be responsible for provoking some pathological features of MS, especially tissues closely located along intestine. We intended to clarify contribution of BAs to the MS pathophysiology. WKAH/Hkm SLc male rats were fed an AIN‐93‐based diet with or without 0.05% cholic acid (CA) for 13 weeks, which would not promote apparent energy expenditure in adipose tissues. We analyzed blood parameters including cytokines and lipids, BA composition in feces, changes in the gut permeability, and gene expressions in some tissues. Significant increases were observed in serum AST, ALT, and TNFa. The CA supplementation increased DCA concentration in feces as well as the gut permeability. These are usually observed in diet induced‐obesity. Interestingly, plasma adiponectin in CA group decreased from 3 weeks without weight gain of adipose tissue. At week 13, TLR4 expression was up regulated in the mesenteric lymph node in the rats fed the CA diet. It is possible that tissues located geometrically close to the intestine are relatively sensitive to BA fluctuation in gut contents, which may result in some pathological features observed in MS.
Elucidating the controlling role of the pyruvate phosphate dikinase regulatory protein on C4 photosynthesis
Authors: Lee Pantera Harrison , Chastain Chris J
Published: June 2021

Pyruvate phosphate dikinase (PPDK) is a C4 photosynthetic pathway enzyme that converts Pyr to PEP, the substrate for CO2 fixation in C4 leaves. PPDK activity is regulated in response to light intensity to ensure the PEP synthesis rate is in balance with the amount of light energy incident on the leaf. Light regulation of PPDK occurs by reversible phosphorylation of an active‐site Thr. A bifunctional protein kinase/phosphotransferase, the PPDK regulatory protein (PDRP), catalyzes this reversible phosphorylation. Although the biochemical properties of PDRP are well known, its role in overall C4 cycle regulation in leaves is unclear. Our approach for resolving this question entails creating PDRP‐RNAi transgenic knockdown maize lines for assessing the interdependence of C4 PS and PDRP>;PPDK regulation. The first phase of the study involved isolation of homozygous PDRP knockdown T2 maize lines. This was accomplished using PCR and qPCR based screen. A total of 22/134 T2 plants were found to be homozygous for the PDRP‐RNAi transgene. A subset of these T2 plants was analyzed for leaf PDRP transcript abundance via Taqman based qPCR assay. This revealed a 5–50% suppression of PDRP transcript vs. Wt. Western blot analysis of leaf extracts showed a corresponding decrease in PDRP protein. Lines showing severe PDRP suppression developed chlorotic leaves and failed to reach maturity, suggesting PDRP is required for optimal C4 PS.
Nutrition & CORonary Artery Disease Prevention (N‐CORP) Study: preliminary results and future steps.
Authors: Gregori Dario , Magnoni Marco , Masson Serge , Gorini Marco , Andreini Daniele , Rossi Maria Grazia , Soriani Nicola , Maggioni Aldo Pietro , Maseri Attilio
Published: June 2021

Plasma lipid levels are recognized as determinants of cardiovascular disease. Dietary interventions should be considered as first line intervention. NCORP study aims at exploring the effect of meal pattern on lipid profile.

Four groups were selected: patients with atherosclerotic plaque (AP) and risk factors (RF) represented by Framingham risk determinants (Group A), patients with AP and without RFs (Group B), patients without AP and with RFs (Group C), patients without AP and RFs (Group D). Participants completed a health and lifestyle questionnaire. Plasma levels of five lipid fractions were determined on samples collected for the CAPIRE study.

Preliminary analyses of 207 patients were considered. No significant association was found between lipid profile and case vs control groups. Satisfactory eating habits were retrieved considering Group B and C, compared with others. No significant association between physical activity patterns and lipid profile was found.

The first results of the study pointed out the importance of dietary habits on RFs development, showing the need to deepen in the following steps of the longitudinal study the study of eating pattern’ on genetic modulation of lipid metabolism.
Effect of omega‐3 fatty acid intake on C‐reactive proteins in African and Haitian Americans with type 2 diabetes
Authors: Huffman Fatma , Vaccaro Joan A , Exebio Joel C , Ajabshir Sahar , Zarini Gustavo G
Published: June 2021

Objective

C‐reactive protein (CRP) has been considered independent risk factor for cardiovascular disease. The aim of the study was to assess the relationships among ethnicity, omega‐3 fatty acid intake (n‐3) and CRP level.

Methods

This was a cross‐sectional study of N=410 African (AA) (n=172) and Haitian (HA) Americans (n=238) with and without type 2 diabetes recruited from Miami‐Dade and Broward counties in Florida, USA using mailing lists and community outreach. Sociodemographics, anthropometrics and blood samples were collected after participants signed informed consent. All dietary variables were collected using a semi‐quantitative food frequency questionnaire.

Results

A two‐way interaction of n‐3 intake and ethnicity was significant for CRP [Model: χ 2 (10) = 66.8 (N=406) p < .001]. AA with low n‐3 intake were more likely to have high CRP (≥ 3 mg/L) than those with high n‐3 intake (>; 2.0 g/day) [OR = 3.17 (1.10, 9.10) p =.031]. Ethnicity (p = .249) and n‐3 intake by diabetes status (p = .132) did not explain CRP.

Conclusion

Future studies are needed to determine the effect of n‐ 3 intake on lowering CRP by ethnicity and diabetes status. Funding was provided by an NIH/NIDDK grant.
Effects of 6‐month lifestyle intervention on the prevalence of Metabolic Syndrome among free living Brazilian adults
Authors: McLellan Katia , Moreto Fernando , Corrente Jose Eduardo , Burini Roberto Carlos
Published: June 2021

Background

The prevalence of Metabolic Syndrome (MetS) has been increasing worldwide.

Objective

The aim of the present study was to evaluate the effects of a six‐month lifestyle intervention on the prevalence of MetS among free living Brazilian adults.

Methods

A prospective community‐based interventional study was conducted with 153 adults. The intervention consisted of weekly group dietary counseling and daily sessions of supervised aerobic exercises. Clinical, anthropometric, fitness, dietary and plasma biochemical assessments were performed at baseline (M0) and after 6 months (M1). Logistic regression was performed in order to determine the odds ratio for developing or ceasing the fulfill criteria for MetS after the lifestyle intervention.

Results

The prevalence of MetS decrease 7.2% after 6‐months intervention mainly due to decreasing trygliceridemia in 13% and hypertension in 15%. The absolute body fat (kg) decreased after the intervention. It was also noticed an increase in dietary fiber and legumes intake, and a decrease in vegetable oil intake. Logistic regression showed a protection of flexibility and a risk factor of vegetable oil and sugar intake for developing MetS over time.

Conclusion

A six‐month lifestyle intervention conferred multiple health benefits in decreasing the prevalence of MetS in individuals at high risk.
Higher Body Mass Index, Lean Body Mass and Fat Mass Obtained by Bioimpedance are Associated with Slower HIV Disease Progression in Asymptomatic HIV+ Adults
Authors: Luisi Sonya , Campa Adriana , Martinez Sabrina Sales , Makhema Joseph , Bussmann Hermann , Farahani Mansour , Marlink Richard , Baum Marianna K
Published: June 2021

Objective

To examine the effects of Lean Body Mass (LBM), fat mass (FM) and Body Mass Index (BMI) on HIV disease progression in 878 asymptomatic ART naïve HIV+ adults in Botswana.

Methods

This study is a secondary analysis of data collected by the parent study, Nutrient Therapy in Botswana. The relationship of CD4 cell count, log10 HIV viral load, BMI, LBM and FM (obtained by bioimpedance) were analyzed by ANOVA and Linear regressions.

Results

Participants with higher LBM, FM and BMI had higher CD4 cell count [β=1.60, p=0.046] [β=1.40, p=0.042] [β=2.51, p=0.045] and lower viral load [β=−0.013, p=0.001], [β=−0.010, p=0.010], [β=−0.019, p=0.003] respectively, controlling for age, gender and physical activity.

Conclusion

These findings suggest that maintaining higher LMB, FM and BMI in HIV‐infected adults may maintain immune function early in the disease. This evidence supports the use of physical activity and adequate caloric and protein intake as effective interventions in HIV+ adults in early stages of the HIV disease to prevent weight loss and maintain adequate lean body mass, fat mass and body mass index.

Funded by NIDA
Diet, physical activity and use of complementary products among cancer survivors
Authors: Park Myungsook , Lee Jung Eun , Kim Dong‐Hyun
Published: June 2021

The aim of this study is to evaluate adherence to recommended dietary and physical behaviors and complementary product use among cancer survivors in Korean. We calculated an American Cancer Society (ACS) adherence score for each participant's assessment of body mass index, physical activity and intake of food groups based on ACS guideline for cancer survivors. Food intake was assessed by using a validated semi‐quantitative food‐frequency questionnaire. We used multivariate polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) and compared ACS adherence scores and use of complementary products between short‐term (less than 5 years) and long‐term (5 or more years since diagnosis) survivors and those who had never diagnosed cancer. Survivors were more likely to follow ACS recommendations and use complementary products than those who had never had cancer. Compared to those who never had cancer, ORs (95% CIs, p for trend) comparing top with bottom quintile of ACS adherence scores were 4.21 (2.96–6.06, <.001) for short‐term survivors and 2.96 (1.97–4.44, <.001) for long‐term survivors. Cancer survivors tended to use complementary products compared to those who had never had cancer. Korean cancer survivors were more likely to use complementary products and adhere to the ACS guidelines entailing healthy dietary and physical behaviors than those who had never had cancer.
Method validation for the measurement of sialic acid and sialyllactose in human milk using high performance anion exchange chromatography with pulsed amperometric detection
Authors: Li Xi , Yachetti Stephen , Burgher Anita M.
Published: June 2021

Sialic acid (SA) is an important component of human milk and occurs both as free SA and bound to oligosaccharides (OSs), proteins and complex lipids. To provide accurate and sensitive analytical methods for determination of SA and sialyllactose, one of the most prevalent sialyllated OSs in human milk, two independent method validations were conducted. The analytes in the first validation were free SA, 3′‐sialyllactose (3′SL) and 6′‐sialyllactose (6′SL). The second validation consisted of measurement of SA after an acid hydrolysis sample treatment to provide the level of human milk SA that occurs as part of OSs, glycoproteins, and complex lipids (total SA). All analytes were quantified using high performance anion exchange chromatography with pulsed amperometric detection (HPAEC‐PAD). Method precision for all analytes is represented by relative standard deviation of less than 11.7% for six replicate analyses on same day, and less than 7.3% for six replicates on three days. Accuracy was demonstrated in pooled quality control samples fortified with analytes at three levels, low, middle and high, where recoveries ranged from 93.9 to 116%. The limits of quantitation are 8.00, 8.00, 3.20 and 40 mg/L; and the limits of detection are 2.89, 2.33, 1.12 and 0.34 mg/L for 3′SL, 6′SL, free SA and total SA, respectively. The validated methods are accurate and sensitive.

Funded by Pfizer Nutrition.
Ischemia‐induced endothelial cell swelling and mitochondrial dysfunction are augmented by the pro‐inflammatory chemokine, MCP‐1, but attenuated by dietary polyphenols in vitro
Authors: Panickar Kiran S , Qin Bolin , Anderson Richard A
Published: June 2021

Polyphenols possess anti‐oxidant and anti‐inflammatory properties. Oxidative stress (OS)and inflammation have been implicated in the pathogenesis of brain edema in cerebral ischemia. OS and pro‐inflammatory cytokines damage endothelial cells/neurovascular unit. The resultant breakdown of the blood‐brain barrier contributes to vasogenic edema and may also contribute to endothelial cell swelling, a component of cytotoxic edema. We investigated the protective effects of polyphenols in bEND3 endothelial cultures subjected to 5 hr oxygen‐glucose deprivation (OGD). A polyphenol‐rich extract from green tea (GT), a polyphenol trimer from cinnamon, and resveratrol prevented the OGD‐induced rise in mitochondrial free radicals, cell swelling, and the dissipation of the inner mitochondrial membrane potential. Monocyte chemoattractant protein (MCP‐1), a chemokine, but not TNF‐α or IL‐6, augmented the cell swelling. The effect of MCP‐1 was attenuated by the polyphenols. Cyclosporin A, a blocker of the mitochondrial permeability transition pore, did not attenuate cell swelling but BAPTA‐AM, an intracellular calcium chelator did, indicating a role of [Ca2+] but not the mPT in cell swelling. These results indicate that the polyphenols reduce mitochondrial ROS and subsequent cell swelling in endothelial cells following ischemic injury and thus may reduce brain edema and associated neural damage in ischemia.
Botanical extracts modulate adipocyte function and insulin sensitivity in vitro and in vivo
Authors: Stephens Jacqueline M , Ribnicky David M , Richard Allison J
Published: June 2021

Historically, many drugs have been developed from plant extracts. The study of botanical extracts is an emerging area in obesity and T2DM research. Botanical extracts are a rich source of molecules capable of modulating adipocyte development and function. Thus, botanicals which alter the properties of fat cells could be protective or causative of obesity, metabolic syndrome and/or T2DM. We used 3T3‐L1 cells and C57BL/6 mice to study the effects of botanicals on adipocytes and adipose tissue. We examined adipogenesis in vitro and insulin action and adipokine secretion in mice. In a screen of botanical extracts for potential novel therapeutic modulators of adipocytes, we identified several positive regulators of fat cell development from the genus Artemisia. Our studies revealed that extracts of several Artemisia species promote differentiation of 3T3‐L1 fat cells and increase adiponectin secretion in mature adipocytes. Additionally, in C57BL/6 mice maintained on a 60% high fat diet, administration of the Artemisia extracts improved insulin‐sensitive Akt serine phosphorylation within white adipose tissue and increased circulating adiponectin levels. In summary, we have in vitro and in vivo data to demonstrate that Artemisia extracts have a beneficial impact on metabolic syndrome by improving adipocyte development and function. Support: PBRC BRC Pilot funding and NIH grant P50AT002776–06 from ODS and NCAAM.
Variations in Plasma Carotenoids from Jersey Cows fed Pasture versus Total Mixed Ration
Authors: Smith Jillian M , Beliveau Amy R , Wenzel Adam J , Curran‐Celentano Joanne
Published: June 2021

Interest in organic milk is increasing. By USDA Certified Organic standards, animals must be fed on pasture for a minimum of 120 days. Research indicates that various factors such as diet impact the nutritional quality and composition of milk. The objective of this study was to understand how feeding practices affected bovine plasma carotenoid concentrations over time. Plasma samples were collected from 9 cows fed on pasture at an organic dairy and from 9 cows fed total mixed ration (TMR) at a conventional dairy. Components were extracted from the plasma and separated via High Performance Liquid Chromatography. Results showed that plasma concentrations of lutein, zeaxanthin, β‐cryptoxanthin, and β‐carotene significantly changed from baseline at each dairy. The changes in plasma lutein, zeaxanthin, α‐carotene, and β‐carotene concentrations were also significantly different between dairies. Plasma lutein, zeaxanthin, α‐carotene, and β‐carotene concentrations were significantly higher in plasma from cows fed on pasture versus cows fed TMR. This suggests that diet and season affect the concentrations of measured components in plasma. These variations could influence the health of the animal and the nutrient composition of the resulting milk.

Grant Funding Source: Hamel Center for Undergraduate Research, NH Agriculture Expermiment Station
The role of dopamine D3 receptors in the discriminative stimulus effects of quinpirole, cocaine, and methamphetamine in rhesus monkeys
Authors: Duke Angela N , Green Heather L , Newman Amy H , Nader Michael A
Published: June 2021

Dopamine (DA) D3 receptors may be a promising therapeutic target for stimulant abuse. Compounds deemed partial agonists in vitro do not typically show D3 agonist effects in vivo. It was recently reported that the D3 partial agonist PG619 elicited yawning in monkeys with an extensive cocaine history to a similar degree as the D3 agonist quinpirole (QUIN). The current experiments investigated the role of DA D3 receptors in three groups of monkeys trained to discriminate QUIN (0.03 mg/kg), cocaine (COC) or methamphetamine (MA), both at 0.1 mg/kg, in a two‐key saline versus drug discrimination (SD) paradigm. PG619 (0.3–10.0 mg/kg) did not substitute for QUIN, but enhanced QUIN‐appropriate responding when given as a pretreatment (3.0 mg/kg), indicating D3 agonist effects. Buspirone (0.03–0.3 mg/kg), a D3 antagonist, substituted for QUIN in 2 of 3 monkeys without decreasing response rates. In COC‐ and MA‐trained monkeys, QUIN did not substitute for the training dose. In preliminary studies, buspirone blocked the SD effects of COC and MA. Taken together, these findings using D3 partial agonists and antagonists suggest a unique pharmacology related to D3 receptor function and support the hypothesis that COC and MA exposure modifies these effects. These studies support the continued exploration of novel D3 receptor compounds for the treatment of stimulant abuse. DA12460, NIDA‐IRP
Neuroprotective effects of Maca extract and macamides against amyloid β peptide induced neurotoxicity in B‐35 neuroblastoma cells
Authors: Lewis Stephanie , Pino‐Figueroa Alejandro
Published: June 2021

The purpose of this study was to determine whether Lepidium meyenii (Maca) extract or its active principles the macamides could ameliorate the neuronal damage produced by the amyloid‐beta (Aβ) peptide in Alzheimer's Disease (AD). We hypothesized that Aβ is toxic to B‐35 rat neuroblastoma cells and that Maca extract or macamides could counteract the induced cell damage. Maca extract and one isolated macamide were tested in cell cultures to determine their protective activity against Aβ induced neurotoxicity using B‐35 cells. The results suggest that there is a concentration dependent toxicity of Aβ in B‐35 neuroblastoma cells. They also suggest that both Maca extract and the macamide 3‐methoxybenzylhexadecanamide are neuroprotective against Aβ induced damage in the mentioned cells. The Maca extract exhibited a concentration dependent neuroprotective effect at all tested concentrations. However, the macamide showed a concentration dependent neuroprotective effect until certain concentration from which higher concentrations were less effective. These results suggest a potential application of macamides from Maca as potential agents for the treatment of AD and other neurodegenerative diseases. Further experiments are necessary to demonstrate the mechanisms of protection against Aβ peptide.
Antimalarial effect of Azadirachta indica (A.Juss Meliaceae) leaf extract complexed with (2‐hydroxypropyl)‐β‐cyclodextrin on Plasmodium berghei in mice
Authors: Ologe Mary Olufunmilayo , Iwalewa Ezekiel Olugbenga , Onyeji Cyprian Ogbonna
Published: June 2021

We investigated the curative activity of Azadirachta indica leaf extract complexed with 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) alone and a combination of (HP‐β‐CD) and polyvinylpyrollidone (PVP) with a view of improving the antimalarial activity of the complex.

Hot aqueous extract (HAE), Hot ethanolic extract (HEE) and Cold ethanolic extract (CEE) of A.indica were prepared and assessed for their suppressive and curative in vivo antimalarial activity, following established procedures. HAE at different doses (50, 100, 200 and 400 mg/kg body weight) was then complexed with HP‐β‐CD (at a ratio 1:1). The complexes were prepared by freeze‐drying method and assessed for their curative in vivo antimalarial activity. The data were analysed.

In the suppressive tests, CEE, HAE AND HEE produced chemosuppression of 75.0%, 78.2% and 77.7% at 400 mg/kg, respectively. HAE at 400 mg/kg produced the lowest percent parasitemia on day 5 in the curaitve tests. HAE ‐ HP‐β‐CD complex at 400 mg/kg dose showed superior efficacy, which was significant ( F[5, 22] = 5.06, p < 0.05), when compared to complexes of the lower doses in the curative tests. In the HAE (400 mg/kg) ‐ HP‐β‐CD – PVP complexes curative activity evaluation, 400 mg/kg extract alone attained 57.9% chemosuppression on day 6 while the extract – CD complex at that dose attained 51.5% suppression of parasitemia. Extract – CD – PVP complexes did not improve the curative activity of HAE.

We concluded that the complexation of an aqueous extract of A. indica leaf with HP‐β‐CD at 400 mg/kg produced significant improvement in the activity of the extract while HP‐β‐CD and PVP complexes did not significantly improve the curative activity.
Effects of HIV‐1 tat protein on excitability of enteric neurons
Authors: Ngwainmbi Joy , Smith Tricia H , Hauser Kurt F , Dewey William L , Akbarali Hamid I
Published: June 2021

HIV is mostly transmitted across mucosal surfaces including vaginal, anorectal and oro‐intestinal mucosa. Recent studies demonstrate that HIV infection affects gastrointestinal motility including diarrhea being a serious problem with significant effect on the quality of life. Trans‐activator of transcription (Tat) is an HIV gene that enhances the efficiency of HIV gene transcription. Tat protein together with GP120 has been shown to induce neuronal death, however, its effects on enteric neuronal excitability is not known. In this study we examined the effect of acute (0–30 min) as well as chronic (up to 48 hrs) administration of Tat (1–86) on the electrical activity of mouse enteric neurons in culture. In whole cell patch clamp studies under current clamp, Tat decreased the threshold for action potential generation by 6.8±0.7mV (n=4) within 10 mins of perfusion and increased the number of spikes for each individual neuron. This effect persisted in neurons pretreated with Tat for over 48 hrs (n=15). In some neurons, spontaneous action potentials were observed. The average resting membrane potential of enteric neurons in the presence of Tat was −49mV (n=15) and not significantly different for untreated cells (‐50mV; n= 15). These data suggest that Tat protein has a direct and persistent effect on neuronal excitability. Supported by NIH DA024009
Vascular SOD levels is more important than Leukocyte Transmigration and Smooth Muscle Cell Activation on Vascular Pathology
Authors: Kar Saptarshi , Kavdia Mahendra
Published: June 2021

Oxidative and nitrosative stress during leukocyte‐endothelial cell interactions lowers activity levels of superoxide dismutase (SOD), causes transmigration of leukocytes into the vascular abluminal region and activation of smooth muscle cells (SMC) to produce NO/ superoxide (O2•−). Information about changes in vascular oxidative and nitrosative stress levels related to lower SOD levels, leukocyte transmigration and SMC activation are elusive. We developed a computational biotransport model for an isolated microvessel segment to quantify the changes in the local NO, O2• − and peroxynitrite levels at different regions of the microvasculature upon onset of the above pathological events. In comparison to severe oxidative stress during leukocyte‐endothelial cell interactions, (i) Reduction of vascular SOD levels caused a significant increase in vascular peroxynitrite and O2• − concentration, (ii) The O2• − and peroxynitrite levels remained similar while the NO concentration in the smooth muscle region increased by 1.4 fold upon leukocyte transmigration and (iii) Activation of smooth muscle cells following leukocyte transmigration did not change vascular NO, O2• − and peroxynitrite concentration. The results show that the contribution of reduced SOD levels to vascular oxidative and nitrosative stress is far greater than transmigration of leukocytes and activation of SMC. Supported by NIH R01 HL084337.
Early protective joint motion influences gene expression in a rat model of anterior cruciate complete rupture
Authors: Kokubun Takanori , Kanemura Naohiko , Maejima Hiroshi , Fujino Tsutomu , Morita Sadao , Takayanagi Kiyomi
Published: June 2021

Objective

The objective of this study was to define how acute anterior cruciate ligament (ACL) complete injury remnant would potentially alter specific mRNA expression of angiogenesis and collagen synthesis factor by early protective joint motion.

Methods

Thirty‐six Wistar rats were divided into 3 groups: Control, Sham operated, and early protective joint motion. In the joint motion group, ACL was surgically transected and then tied up the joint with nylon string to put brake on forward slides. Each group of 4 rats was sacrificed at 1 day, 3 days, and 5 days postoperatively. Total RNA from the ACL remnant was reverse transcribed into cDNA. Real‐time RT‐PCR was performed using rat specific primer sets for COL 1, COL 3, VEGF and housekeeping gene (B‐actin). Differences in the Ct values between the tested mRNA and the B‐actin mRNA were calculated to determine the relative expression revels.

Result

In the early protective joint motion group, mRNA levels for COL 1 and COL 3 increased all time‐points (1 day, 3 days, and 5 days) and 2 time‐points (1 day, and 3 days), respectively. No significant differences in VEGF mRNA expression were found in this protocol.

Discussion

In the present study, we demonstrated acute ACL complete rupture remnant has healing potential. Furthermore controlling malfunction and inducing normal joint movement in acute stage make it possible.
Functional capillary recruitment during cephalic phase of digestion is blunted in obesity
Authors: Buss Caroline , Kraemer‐Aguiar Luiz Guilherme , Maranhão Priscila Alves , Bouskela Eliete
Published: June 2021

Context

In healthy subjects, functional capillary recruitment (FCR) occurs during the cephalic phase of digestion (CPD), suggesting a precocious role for the microcirculation in the physiology of digestion and nutrient homeostasis.

Objective

To investigate if such response is present in obese subjects.

Methods

Twenty‐nine obese subjects, 28.6±2.8 years (mean±SD) and BMI of 36.7±2.2 kg/m2, were randomized into receiving cognitive‐sensorial stimuli of a breakfast tray to elicit CPD (CPD group, n=15) or not (control group, n=14), after a 12‐h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm2) evaluated by videocapillaroscopy. Saliva assessment was used as a clinical marker of successful CPD stimulation.

Results

No significant difference was detected on basal (53.6±12.8 to 52.3±8.9, p=0.621) and peak FCD (58.5±10.6 to 55.7±9.4, p=0.239) in the CPD or in the control group. Saliva secretion significantly increased in the CPD (9.3±8.5 to 13.4±8.4 mm, p=0.015) and remained unchanged in the control group.

Conclusions

FCR during CPD is blunted in obesity and the increment in saliva secretion indicates responsiveness to the sensorial stimuli. Mechanisms involved in this response should be further investigated.

Research Support: Coordination for the Enhancement of Education Personnel (CAPES); State of Rio de Janeiro Carlos Chagas Filho Research Foundation (FAPERJ)
Impaired vasodilation of human obese visceral resistance arteries is improved by apocynin through hydrogen peroxide and activation of SK and IK channels
Authors: Bian Jing‐Tan , Szczurek Mary , Robinson Austin T , Phillips Shane A
Published: June 2021

Previous studies indicate that in human obesity, visceral adipose tissue (VAT) is associated with endothelial dysfunction compared to subcutaneous adipose tissue (SAT). We hypothesized that inhibition of NADPH oxidase will reverse impaired Flow‐induced dilation (FID) in resistance arteries of VAT. Arterioles were dissected from VAT and SAT biopsies (BMI: 48±2, n=15) and cannulated for measurements of luminal diameters. Maximum dilations to papaverine (10−4 M) were determined. Production of hydrogen peroxide (H2O2) was measured by fluorescence microscopy. FID was reduced in VAT to 38±4% (p<0.01, at 60 cm H2O pressure gradient) compared to SAT (92±4%). Apocynin restored FID (73±5%) in VAT and had no effect in SAT. PEG‐catalase abolished the restored FID in the presence of apocynin. Incubation with apamin and tram‐34, blockers of small (SK)‐ and intermediate (IK)‐ conductance, Ca2+‐activated potassium channels, respectively, decreased this restored FID. Improved FID induced by the SK channel opener CyPPA was blocked by apamin. Flow‐ induced H2O2 generation was increased (1.7 fold) in the presence of apocynin compared to baseline and PEG‐catalase attenuated this increase. Taken together these data suggest that H2O2 and the activation of SK and IK channels contribute to the restored effect of apocynin on flow induced dilation in visceral fat during obesity. NIH (R01HL095701).
Tiron, a superoxide scavenger, suppresses fictive locomotionevoked sympathoexcitation in rats with heart failure
Authors: Koba Satoshi , Inoue Yumiko , Hisatome Ichiro , Watanabe Tatsuo
Published: June 2021

We have previously reported that fictive locomotion‐evoked sympathoexcitation in rats with heart failure was exaggerated and that this exaggeration was suppressed by Tempol, a superoxide dismutase mimetic, injected bilaterally into the rostral ventrolateral medulla (RVLM). It should be noted that Tempol also possess a property to open ATP‐sensitive and Ca2+‐activated K+ channels. In the present study, we tested if Tiron, which does not chemically relate to Tempol but has a similar superoxide scavenging activity, injected bilaterally into the RVLM of rats with heart failure would reduce fictive locomotion‐evoked sympathoexcitation. Heart failure was induced in rats by coronary artery ligation. Fictive locomotion was evoked in decerebrated and paralyzed rats by electrical stimulation of the mesencephalic locomotor region. In the rats with heart failure (N8, fractional shortening < 35%), Tiron mirrored the effect of Tempol; bilateral injection into the RVLM of Tiron (10 mM, 100 nl) significantly (P<0.05) reduced the renal sympathoexcitatory and pressor responses to fictive locomotion by 42% and 43%, respectively. The present data support the concept that oxidative stress in the medulla of heart failure plays a role in excessively amplifying central command‐mediated sympathoexcitation. Supported by Mitsui Life Social Welfare Foundation Research Grant (to S. Koba).
Insulin Resistance due to Nutrient Excess: Mechanisms of AMPK Downregulation
Authors: Saha Asish K , Balon Thomas W , Coughlan Kimberly A , Ruderman Neil B
Published: June 2021

Excesses of glucose and the branched chain amino acids lead to insulin resistance in skeletal muscle by activating mTOR/p70S6 kinase (p70S6K). In a recent study we demonstrated that glucose and leucine may produce these effects by downregulating AMP‐activated protein kinase (AMPK) which, when activated, diminishes mTOR/p70S6 K signaling. How these excesses of glucose and leucine decrease AMPK activity is unclear, since they do not alter the cell's energy state (AMP/ATP or CrP). We explored whether the decrease in AMPK activity might be due to decreases in the activity of SIRT1, a histone protein deacetylase that can activate AMPK or by changes in the activity of an unidentified kinase or phosphatase that results in the phosphorylation of Ser485/491 on the catalytic subunit of AMPK leading to its inhibition. Incubation of extensor digitorum longus muscle, with high glucose (25 mM) or 5 mM glucose and leucine (100 μM) persistently diminished AMPK activity within 30 min an effect that lasted for 2 h. Likewise both high glucose and leucine decreased the activity of SIRT1as reflected by increases in the deacetylation of histone H3 and a decrease in the activity of the rate‐limiting enzyme for SIRT1 activation, nicotinamide phosphoribosyltransferase (NAMPT). In addition, SIRT1 abundance was decreased. These changes only become evident after 2 h, however. In contrast, excess glucose and leucine caused increased phosphorylation of AMPK at Ser485/491 after 1 h. In studies with intact rats, we found that prolonged (3–8 h) hyperglycemia, produced by a glucose infusion, downregulates AMPK Thr172 phosphorylation and causes insulin resistance as early as 3 h. However, SIRT1, AMPK (Ser485/491) and NAMPT activity only decreased between 5–8 h. The results indicate that both leucine and high glucose downregulate AMPK by at least two mechanisms. This could account for sustained decreases in AMPK activity; however, temporally they do not account for the initial decrease in AMPK activity caused by these fuels.
The role of STIM1 and store operated calcium entry in glucose‐induced insulin secretion
Authors: Zou Luyun , Chatham John C
Published: June 2021

Calcium plays an important role in contributing to glucose homeostasis by regulating insulin secretion in β‐cells, primarily through activation of voltage gated calcium channels. Interestingly, STIM1 and Orail1 proteins, which regulate store operated calcium entry (SOCE) are present in β‐cells; however, the role of SOCE in β‐cells is unknown. Therefore the goal of this study was determine whether STIM1 plays a role in regulating glucose induced insulin secretion and if so whether this was affected by increased O‐GlcNAc levels. We found that STIM1, STIM2, and Orail1 proteins, the molecular machinery for required SOCE, were present in INS‐1 cells. To evaluate the role of STIM1 on insulin secretion INS‐1 cells were either transected with a STIM1 adenovirus over night or pre‐treated with SKF96365 (SKF, 5μM), an inhibitor of SOCE for 2 or 4hrs. Cells were preincubated with 3mM glucose for 2hrs followed by 15mM glucose to induce insulin secretion. STIM1 overexpression had no effect on glucose‐induced insulin secretion; however, SKF treatment (4hrs) decreased insulin secretion almost 2‐fold (p<0.05). These data suggest that SOCE may contribute to glucose‐induced insulin secretion in INS‐1 cells, however further studies are needed to confirm the effects of SKF.
Human mesangial cells treated with lipopolysaccharide mimicking human sepsis are able to produce catecholamines
Authors: Magalhaes Dayane Cabo Grosso Peralta , Arita Danielle Yuri , Aragão Daniellle Sanches , Almeida Waldemar Silva , Casarini Dulce Elena
Published: June 2021

Mesangial cells (MC) have the entire machinery for the production of catecholamines (CA) and are able to express mCD14, a component of the receptor lipopolysaccharide (LPS) that is associated with type Toll like 4 receptor on the cell surface. The LPS in sepsis can trigger acute renal failure. We aimed to evaluate production/release of CA by immortalized human mesangial cell (HMC) treated with LPS. The HMC were cultured in DMEM with 10% fetal bovine serum. Then incubated with DMEM without FBS for the experiments in presence of LPS. The CA and cofactor tetrahydrobiopterin (BH4) were quantified using HPLC. The enzymes as tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and dopamine ƒÒ‐hydroxylase (DƒÒH) were detected by Western blotting. Incubation of HMC with LPS 100 ƒÝg/ml increased intracellular levels of L‐DOPA and dopamine, and at the same time reduced the concentration of AD and L‐DOPA in the extracellular. There was an increase in expression of TH in HMC incubated with LPS 100 ƒÝg/ml that was correlated with the levels of CA. BH4 levels in extracellular compartment are directly related to increased levels of CA in the cells treated with LPS. CA are involved in various physiological processes in the kidney, being factors that impact on renal hemodynamics. Our results suggest that LPS can influenciate the production/release of CA in HMC. (supported by Fapesp and CAPES)
Suppression of inflammatory cytokines in the kidney during chronic high salt intake in wild type and e‐NOS knockout mice
Authors: Singh Purnima , Castillo Alexander , Majid Dewan S A
Published: June 2021

Inhibition of systemic nitric oxide (NO) production reduces interleukin (IL‐10) and increases tumor necrosis factor‐α (TNF‐α) level in the kidney. However, the status of inflammatory cytokines during chronic high salt (HS) intake, particularly in NO deficient condition, is not yet clearly known. In the present study, we measured the renal levels of pro‐ (TNF‐α and IL‐6) and anti‐ (IL‐10) inflammatory cytokines after HS (4% NaCl for 2 weeks) intake in both wild‐type (WT, C57BL/6) and e‐NOS knockout (KO) mice (~8 weeks old, n=6 in each group) and compared these findings with those in mice with normal salt intake (NS; 0.3% NaCl). The kidneys were collected under anesthesia at the end of experimental period and the cytokine levels were measured in homogenized renal tissues using ELISA kits. Mean arterial pressure (tail‐cuff plethysmography) was increased in KO (111±4 to 136±8 mmHg) but not in WT (99±5 to107±4 mmHg) after HS intake. The renal level of cytokines (expressed in pg/mg protein) during NS intake were significantly higher in KO (TNF‐α, 624±67 vs 325±73; IL‐6, 619±106 vs 166±61; IL‐10, 6087±567 vs 3929±378) compared to those in WT. However, HS intake significantly lowered the levels of these cytokines both in WT (TNF‐α, 114±17; IL‐6, 81±14; IL‐10, 865±130) and in KO (TNF‐α, 115±18; IL‐6, 56±7; IL‐10, 882±141). These data demonstrate that chronic HS intake suppresses both pro‐ and anti‐inflammatory cytokines levels in the kidney in intact as well as in eNOS deficient condition. (NHLBI #66432)