bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of overweight and obesity in patients receiving psychopharmacological placed in long‐stay units (1A and 1B) from Psychiatric Hospital “Dr. Samuel Ramirez Moreno “
Authors: Zamarripa Carlos Alberto Jiménez , Rodríguez Marco Antonio Estrada , Luna Oscar Meneses , Muñoz Marlen Gómez , García Carlos Rivera , Mendoza Claudia Camelia Calzada 
Published: June 2021

IntroductionIt is well known that patients with severe mental illness often have metabolic alterations and therefore can develop co‐morbidities, which reduce their life expectancy compared with general population. In addition, they intake drugs that induce overweight and obesity, which is a risk factor for diseases such as metabolic syndrome.ObjectiveIdentify the association between overweight and obesity with consumption of psychotropic drugs in patients in long‐stay units (1A and 1B) from Psychiatric Hospital “Dr. Samuel Ramirez Moreno”.Results17.8% and 8.3% of patients had obesity in units 1A and 1B, respectively. Additionally, the BMI was similar in both groups and there was no relationship between BMI and number of psychotropic drugs consumed. Before indicates that dietary management is effective in the control BMI of patients, despite having predisposing factor to obesogenics psychoactive drugs, suggesting lower risk of developing co‐morbidities.ConclusionsPsychiatric patients units 1A and 1B, have an incidence of overweight and obesity lower than the national average.
Obesity and insulin resistance, risk factors for gingivitis in children?
Authors: Friedman Silvia , Casavalle Patricia , Gonzales Chaves Maria M. , Antona Maria E. , Lifshitz Fima , Rodriguez Patricia 
Published: June 2021

Insulin resistance (IR) may be present in overweight/obesity (O/O). Obesity and periodontitis were studied in adults. Our aim was to evaluate whether IR in (O/O) children was associated with gingivitis. A cross‐sectional, prospective, observational, descriptive and a comparison study of independent samples were undertaken. Thirty‐four children between 8–14 years of age with diagnosis of O/O attending the Pediatrics Section of Buenos Aires Hospital, were included. Based on HOMA, children were grouped according to HOMA>;2.5 (IR) and below it was non IR (NIR). Plaque index (IP) (Silness‐Loe,1964), gingival index (GI) (Loe‐Silness,1963) and bleeding on probing (BoP) (Muhlemann, 1975), were recorded. Fischer‐test, p<0.05.ResultsHOMA>;2.5 was found in 50% O/O children. In IR, PI=57.2%(28.8–82.3) vs. 42.8 % (17.6–71.1)(p=0.728), GI=54.8%(36.0–72.6)vs. 45.2%(27.4–63.9)(p=0.227) and BoP=70.6%(41.0–86.7)vs. 29.4%(10.3–56.0)(p=0.038). These results suggest a high prevalence of IR in O/O children, associated with oral manifestations. New studies will be designed to establish whether the progression of gingivitis in IR children is favored by the systemic disease. Awarded by UBACyT 20020100100613 & CO02.
Effects of acute Pils‐beer consumption on alcohol‐induced liver steatosis in a mouse model
Authors: Landmann Marianne , Kanuri Giridhar , Bergheim Ina 
Published: June 2021

Chronic alcohol abuse is still among the leading causes of liver‐related diseases worldwide. Studies suggest that not only the amount but also the type of alcoholic beverage may be critical in the development of alcoholic liver diseases. In the present study, the acute effects of Pils‐beer and plain ethanol intake on the liver were determined.C57Bl/6J mice either received a bolus ethanol, beer (6 g/kg BW, isocaloric) or maltodextrin solution. Fat accumulation, markers of lipogenesis and mRNA expression of MyD88 as well as concentration of 4‐hydroxynoneal protein adducts (4‐HNE), protein levels of the inducible NO synthase (iNOS) and ApoB were analyzed in livers 6h after the acute alcohol exposure.Despite similarly elevated plasma alcohol levels in both alcohol exposed groups, acute ethanol exposure caused a ~5‐fold increase (p<0.05) in hepatic lipid accumulation while the ingestion of beer only lead to a ~2‐fold increase (n.s.) in comparison to controls. The less harmful effects of the beer were associated with a protection against an elevation of MyD88, SREBP‐1c and FAS mRNA expression as well as the increase of iNOS protein levels and 4‐HNE protein adducts in the liver. Protein levels of hepatic ApoB were significantly induced of Pils‐beer but not ethanol‐treated mice.Taken together, these data suggest that the acute ingestion of Pils‐beer may be less harmful on the liver than ethanol in mice.
Identification of miR‐26b and miR‐203 gene targets in colon cancer cells
Authors: Shah Manasvi Shailesh , Davidson Laurie A , Chapkin Robert 
Published: June 2021

We recently demonstrated that the unique combination of chemoprotective dietary fish oil (containing eicosapentaenoic acid and docosahexaenoic acid) plus pectin (fermented to butyrate in the colon) upregulates a subset of rat mucosal miRNAs, miR‐19b, miR‐26b and miR‐203, and downregulates their predicted target genes PTK2B, PDE4B and TCF4 as compared to a corn oil cellulose diet in the presence of carcinogen. To further elucidate the biological effects of diet and carcinogen on miRNAs and their targets and to validate the predicted miRNA:mRNA associations, we manipulated miRNA levels by conducting loss and gain of function analyses in the human colon cancer cell line HCT116 and measured changes in protein expression of the targets. Furthermore, using luciferase reporter assays, we demonstrated that PDE4B and TCF4 are direct targets of miR‐26b and miR‐203, while PTK2B is an indirect target of miR‐19b. In addition, the physiological function of these miRNAs was assessed by examining effects on apoptosis and cell proliferation, showing that these miRNAs increased apoptosis. This is the first report to show the chemoprotective effects of combined fish oil and pectin feeding antagonize the oncogenic effects of carcinogen, in part, by modulating the expression of colonic miR‐19b, miR‐26b and miR‐203 and their targets.Grant Funding Source: CPRIT grant RP100473 and NIH grants CA168312, CA129444 and CA59034.
SELECTIVE INHIBITION OF GLIADIN IMMUNE REACTIVITY BY TRANSAMIDATION OF WHEAT FLOUR WITH MICROBIAL TRANSGLUTAMINASE
Authors: Iaquinto Gaetano , Lombardi Emanuela , Bergamo Paolo , Maurano Francesco , Bozzella Giuseppina , Luongo Diomira , Mazzarella Giuseppe , Aufiero Vera Rotondi , Rossi Mauro 
Published: June 2021

Celiac disease (CD) is an immune‐mediated enteropathy caused by the ingestion of wheat gluten. The modification of gluten by intestinal tissue transglutaminase (tTGase) plays a crucial role in CD pathogenesis. In this study, we observed that extensive transamidation of wheat flour with lysine ethyl ester (K‐C2H5) by microbial TGase (mTGase) yielded water‐soluble (spf) and insoluble transamidated gliadin (K‐gliadins) fractions. Using DQ8 transgenic (tg) mice as a model of gluten sensitivity, we observed a dramatic reduction in IFNγ production in gliadin‐specific spleen cells challenged with spf and K‐gliadins in vitro (N=12; median values: 813 vs. 29 and 99; control vs. spf and K‐gliadins, P=0.012 for spf, P=0.003 for K‐gliadins). We also observed an increase in the IL‐10/IFNγ protein ratio (N=12; median values: 0.3 vs. 4.7, control vs. spf, P=0.005). In intestinal biopsies from untreated CD patients challenged in vitro with gliadins (N=10), K‐gliadins dramatically reduced the levels of antigen‐specific IFNγ mRNA in all specimens responsive to native gliadins (4/10; P <0.05). In addition, the analysis of glutathione‐S transferase (GST) and caspase‐3 activities in the enterocytic Caco‐2 cells showed that neither activities were modified by flour transamidation.In conclusion, we found that K‐C2H5 cross‐linking via mTGase specifically affected gliadin immunogenicity, reversing the inducible inflammatory response in models of gluten sensitivity without influencing the cytotoxic properties of gliadins.
The mechanism of CD99 and CD99L2 in leukocyte transendothelial migration
Authors: Watson Richard L , Mikhailov Alexei , Muller William A 
Published: June 2021

Transendothelial migration (TEM) is the process by which leukocytes move out of the vasculature into the interstitium and is one the most important steps of the inflammatory response. PECAM and CD99 are two critical proteins that function sequentially to regulate TEM (PECAM upstream of CD99). These proteins partially reside in a novel, intracellular endothelial cell compartment, known as the Lateral Border Recycling Compartment (LBRC), which supplies the migrating leukocyte with unligated proteins to facilitate its movement through the endothelium, in a process called targeted recycling (TR). Blocking PECAM function has been shown to inhibit TR and subsequently prevent TEM. Here we show that TR is able to be initiated in the face of a CD99 block. We hypothesized that CD99 regulates further rounds of LBRC recruitment. Stimuli that also lead to intracellular membrane recruitment such as histamine (and in preliminary experiments, VEGF) selectively overcome CD99 blockade (but not PECAM blockade), in a calcium‐independent manner. A novel paralog of CD99, CD99L2, has been shown to control inflammation in mice. We show that human CD99L2 functions at the same step as CD99. We are currently investigating if CD99L2 also resides in the LBRC and the mechanism behind its function.This research was supported by R21 HL102519, R01 HL046849, and R37 HL064774 to WAM.
The Role of TLRs in Cardiac Myocyte Apoptosis
Authors: Heiserman James P. , Chen Le , Kim Bum‐Soo , Kim Se‐Chan , Tran Alice , Siebenborn Nina , Knowlton Anne A. 
Published: June 2021

Recently, Toll‐like receptors(TLRs) have been investigated for their role in apoptosis. Previously we have shown that low endotoxin extracellular(ex) HSP60 causes cardiac myocyte apoptosis, and we hypothesized that this would be blocked in cardiomyocytes that have nonfunctioning TLR4.MethodsWe studied adult cardiac myocytes from C3H/HeJ mice, which have a mutant, nonfunctional TLR4, and compared the results with parallel studies in adult cardiac myocytes from wild type (WT) mice. We also looked at the response of WT mouse cardiomyocytes to hypoxia/reoxygenation(H/R) in the presence of TLR2 and TLR4 blocking antibodies. LDH release and NADPH Oxidase 2 (NOX2) activity were endpoints.ResultsWe found exHSP60 caused apoptosis in WT, but not TLR4 mutant cardiomyocytes, based on increased DNA fragmentation and caspase3 activation. In experiments with WT myocytes treated with TLR2 and 4 blocking antibodies with H/R, LDH release was decreased by either blocking antibody. NOX2 activity increased in control cells with H/R and was decrease in WT cardiomyocytes treated with TLR2 and 4 blocking antibodies, suggesting TLR2/4 mediate increased NOX2 activity in H/R injury.
Effect of Pretreatment with Polyalthia longifolia var (Annonaceae) on Isoproterenol Induced Cardiotoxicity and Cardiac Hypertrophy in Rats
Authors: Ramesh Alluri , Rajashekar Perusomula 
Published: June 2021

The Objective of present study was to investigate the effect of pretreatment with Polyalthia longifolia var PL on Isoproterenol induced cardiotoxicity and cardiac hypertrophy in Rats.MethodWistar rats 220–250 g were randomly divided into 5 Groups.Control (olive oil 2 mL/kg orally for 18 days & water IP from days 9–18);ISO group (olive oil 2 mL/kg orally 18 days & ISO 1 mg/kg IP from days 9–18);(PL 300 mg/kg p.o 18 days + ISO);(PL 600 mg/kg p.o 18 days + ISO);Group V (CoQ10 100 mg/kg p.o 18 days + ISO).ISO 1 mg/kg IP was administered in group Groups II, III, IV, V from days 9–18). Twenty‐four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro‐orbital puncture for estimation of serum creatine kinase‐MB CK‐MB, lactate dehydrogenase LDH levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 4 animals from each group were used for estimation of superoxide dismutase SOD activity, reduced glutathione GSH concentration, lipid peroxidation LPO, malondialdehyde MDA, and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician.ResultsISO‐treated rats had a significant change in the endogenous antioxidants significantly higher myocardial MDA concentration significantly lower myocardial GSH concentration and SOD activity and significantly higher serum activities of marker enzymes CK‐MB and LDH. Compared with the ISO group, the PL 600 mg/kg + ISO group had a significant changes in the endogenous antioxidants higher myocardial GSH concentration and SOD activity; significantly lower serum activities of marker enzymes CK‐MB and LDH.ConclusionPretreatment with PL 600 mg/kg for 18 days was associated with moderate protection against ISO‐induced cardiac hypertrophy.
Isoform Selectivity of Adenylyl Cyclase Inhibitors and Identification of Novel Compounds
Authors: Brand Cameron S. , Hocker Harrison J. , Gorfe Alemayehu A. , Cavasotto Claudio N. , Dessauer Carmen W. 
Published: June 2021

Nine membrane‐bound adenylyl cyclase (AC) isoforms produce the 2nd messenger cyclic AMP (cAMP) in response to a wide‐range of stimuli. Reduction of AC activity has well documented benefits, including for heart disease and pain. These roles have inspired development of isoform selective AC inhibitors, a lack of which currently limits exploration and/or treatment of dysfunctions where cAMP plays a role. Known AC inhibitors were flexibly docked to the catalytic site of two AC structure models. Predicted conformations of selective inhibitors suggested flexible catalytic site subregions which confer potency and selectivity. To identify and characterize novel AC inhibitors, a structure‐based virtual screen of 35,000 small drug‐like molecules produced 100 high scoring molecules tested for AC inhibition in vitro. Multiple candidates showed AC inhibition, including isoform selective AC inhibitors. Most known inhibitors are nucleotide analogs; our identified inhibitors show no significant similarity in chemical structure, demonstrating novel selective targeting of the AC catalytic site.Research was funded by Keck Center training fellowship NIGMS T32GM089657 (CSB), and by NIH grants GM60419 and MH060397 (CWD).
Plasmodium falciparum cyclin G associated kinase as a drug target
Authors: Harmse Leonie , Coetzer Theresa 
Published: June 2021

Kinases have become attractive drug targets in disease and several selective inhibitors are currently in clinical use. A P. falciparum kinase gene (PFL2280W) was identified in silico and investigated as a potential novel drug target. PFL2280W shows 57% similarity to mammalian cyclin G associated kinase (cGAK) which is essential for the survival of developing and mature mice.The P. falciparum 3D7 strain was maintained in culture and DNA was isolated and used to amplify the catalytic domain and flanking region of the PfcGAK gene by PCR. The PCR product was cloned into a vector that yielded a fusion protein with a N‐terminal HA and a C‐terminal His (6X) tag respectively. Protein expression was induced in E. coli and isolated by affinity chromatography on Ni+ beads. The protein samples were analysed by SDS‐PAGE and Western blotting using antibodies against the 6xHis and HA tags. The function of the fusion proteins was assessed in a standard kinase assay using radiolabelled ATP and exogenous substrates.Recombinant PfcGAK showed kinase activity using casein as substrate. PfcGAK was shown to undergo autophosphorylation. PfcGAK has a typical serine/threonine catalytic domain except for the absence of the conserved glycine triad in subdomain 1. Bioinformatic analysis of PfcGAK revealed an unique repetitive nanomeric amino acid sequence of 81 amino acids (KLQND/ED/VSG) which occurs outside the catalytic domain. In one clone this repetitive sequence was deleted in frame, which enhanced the production of the recombinant protein. PfcGAK shows the presence of a conserved GOLD domain which indicates that it may function in the Golgi complex, protein sorting or protein‐protein interactions. The carboxyl terminus has a predicted prenylation site, implying that the protein may be anchored in a membrane. Further studies are required to elucidate the potential of PfcGAK as a drug target in P.falciparum. .
Norepinephrine mediated sympathetic over‐activity: the relationship to sodium homeostasis and blood pressure regulation.
Authors: Wainford Richard David , Kuwabara Jill Toshiko 
Published: June 2021

AimRecent controversial studies in mice have suggested excess norepinephrine (NE) mediated sympathetic activity evokes impaired NCC mediated sodium homeostasis and salt‐sensitive hypertension. These studies examined the impact of excess NE on salt‐sensitivity and sodium homeostasis in conscious Sprague‐ Dawley (SD) rats.MethodsNaïve male SD rats or rats receiving a s.c. NE infusion (600ng/min) were maintained on a normal 0.4% (NS) or high 8% NaCl (HS) diet for 14‐days, additional rats received s.c. hydrochlorothiazide (HCTZ 4mg/kg/day) and NE. On day‐14 MAP, 24h Na balance, FENa, MAP response to i.v. hexamethonium (30mg/kg), and peak natriuresis to i.v. HCTZ (2mg/kg) or amiliroide (2mg/kg) infusion was assessed (N=4/gp).ResultsNE increased MAP, FENa and vascular sympathetic tone. HS exacerbated NE induced hypertension, reduced FENa and prevented a salt stimulated reduction in HCTZ evoked natriuresis ‐ HCTZ co‐infusion abolished the salt‐sensitive component of NE stimulated hypertension.

Naive
s.c. NE
s.c. NE + HCTZ

NS
HS
NS
HS
HS

MAP (mmHg)
127±2
129±2
151±3φ
172±4* ≠
152±3 ≠ τ

24h Na+ balance (meq/day)
0.2±0.1
0.3±0.1
0.1±0.1
1.1±0.2* ≠
−0.7±0.3≠ τ

FENa (%)
0.60±0.1
0.93±0.1*
2.3±0.4φ
1.4±0.1* ≠
4.1±0.8 ≠ τ

Peak ΔHR to hexamethonium (mmHg)
−30±3
−32±4
−58±6φ
−52±8≠
−55±5≠

Peak ΔUNaV to Amiliroide (μeq/min)
7.7±0.7
4.2±0.9*
9.4±1.1
3.7±1.6*
7.1±1.1 ≠ τ

Peak ΔUNaV to HCTZ (μeq/min)
9.8±0.2
7.0±0.3*
11.1±1.1
10.8±0.4≠
0.4±0.2 ≠ τ

p<0.05 vs respective NS gp,
p<0.05 vs naïve NS gp,
p<0.05 vs naïve HS gp,
p<0.05 vs NE + HS gp.

ConclusionThese data support previous studies in mice and highlight an apparent opposing interaction between excess NE and high sodium intake on FENa and sodium homeostasis – which exacerbates NE‐induced hypertension via a mechanism independent of NE‐mediated vascular constriction that, as reported in mice, appears to involve altered function of the renal NCC channel ‐ HL107330.
Age‐related cerebrovascular endothelial dysfunction is associated with cognitive impairment in C57BL/6 mice
Authors: Asano Shinichi , Seals Douglas R , Zigler Melanie C , Justice Jamie N , Weber Stewart A , Yoshizawa Mutsuko , Sindler Amy L 
Published: June 2021

Mild cognitive impairment (MCI) is an age‐related disorder that contributes to a reduced quality of life in older adults. However, the underlying mechanisms contributing to MCI with aging are incompletely understood. We tested the hypothesis that old C57 male mice demonstrate cerebrovascular endothelial dysfunction associated with MCI. Endothelium‐dependent dilation (EDD) (ex vivo dilation of mid cerebral and posterior communication arteries to acetylcholine [ACh]) was impaired in old (O: 22–26 mo, n= 17) vs. young (Y: 3–6 mo, n=11) mice (51.2 ± 5.9 % vs. 72.4 ± 5.4 %, p<0.05), and this was associated with reduced L‐NAME‐sensitive dilation (O: 16.1 ± 9.1 % vs. Y: 49.5 ± 9.5 %, p<0.05). Basal NO inhibition by L‐NAME had no effect on phenylephrine‐induced vasoconstriction in O (Con. 23.1 ± 2.8 % vs. L‐NAME 31.1 ± 4.1 %), but increased constriction in Y (Con 19.9 ± 3.1 % vs. L‐NAME 38.0 ± 3.9 %, p<0.05). O (n = 7) had impaired spatial learning during the Morris water maze test (p<0.05) and this was unrelated to differences in vision. In the probe trial, O had lower platform crossing numbers than Y (n =8) (O: 2.7 ± 0.5 vs. Y: 5.1 ± 0.7, p<0.05), suggesting O had impaired spatial memory compared to Y. These results indicate that cerebrovascular endothelial dysfunction, as reflected by reduced basal NO production and NO‐dependent EDD, develops with aging and is associated with MCI in C57 mice.Work supported by NIH AG013038 and AG000279.
Intermittent oxygen inhalation increase maximal workload and maximal heart rate in elite athletes
Authors: Lindholm Peter , Boberg Olle , Frånberg Oskar , Larsson Åke , Gullstrand Lennart 
Published: June 2021

OBJECTIVERecent studies on pulmonary shunt during exercise suggest that oxygen per se could close shunts and thus increase arterial PO2. We hypothesized that a small increase in intrapulmonary PO2 (5–10kPa) would suffice to get performance enhancing effect of oxygen. We also hypothesized that intermittent addition of 10–20l/min of oxygen to inspired air could yield this increase without using premixed gas in athletes ventilating 150–250 l/min.Methods7 athletes were tested on an ergometer cycle in a blinded cross‐over design on two separate occasions. Tests were done on two sub‐maximal workloads (160 and 240W) and thereafter a VO2max test increasing workload by 22.5W/min until exhaustion. Measurements included VO2max(air), heart rate, SaO2. O2 or Air was added intermittently to the inspired air with one exercise protocol ending with air and the other with oxygen. O2 was added at 10–20 liters/minute by an apparatus developed by Oxelerate™, Sweden.RESULTSMax workloads were 437(58)W (Mean(SD)) with air and 453(57)W with O2, p<0,001. Maximal heart rate were 188 (12) beats/min with air and 192(12) with O2 (p<0,001). VO2max(air) were 5,18(0,76)L/min. End‐tidal FO2 was 21,23(0,52)% at maximal workload with O2 addition.CONCLUSIONSThese data suggest that intermittent addition of oxygen to the inspired air is enough to increase work performance and maximal heart rate in highly trained athletes.
Acute Immune Responses to Prolonged Exercise in Environmental Extremes
Authors: Hassan Emad Shaban , Tabba Hani D 
Published: June 2021

This study is to investigate the effect of prolonged exercise with and without a thermal clamp on leukocyte cell, stress hormones, and cytokine responses. Fifteen healthy male volunteers ( means ± SD: age 22 ± 3yr; mass 75.8 ± 3.2kg; maximal oxygen uptake 55 ± 7ml/min/kg) randomly completed four chamber trials of 1 hour each, in different environment and separated by 7 days. Trials were: 1. exercise induced heating (EX‐Heating: temperature/humidity, 38°C/50%); 2. exercise with a thermal clamp (EX‐Cooling: temperature/humidity, 18°C/ 50%); 3. passive heating (PA‐H: temperature/ humidity, 38°C/ 50%); 4. passive cooling (PA‐C: temperature/ humidity, 18°C/50%). EX‐H and EX‐C were composed of 1h treadmill runs at 80% Individual anaerobic threshold (IAT). Blood samples were collected at pre‐post, and 1h post environments exposure. Compared to EX‐H, exercise‐induced increases in core temperature, heart rate, cortisol, human growth hormone, Interleukin‐6, leukocyte and monocyte counts were significantly (p≤0.01) more pronounced after EX‐C. Our results suggest that the additional impact of elevated ambient temperatures on stress responses to endurance exercise in trained subjects seems to affect primarily the hormonal systems and resulting changes in leukocyte number, monocyte and interleukine‐6.This study was supported by the King Saud University