bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Bilateral Ureteral Duplication: an Incidental Finding in Cadaveric Dissection
Authors: Syed Mohsin , Akhter Noor , Phelan Kevin D , Eltahawy Ehab 
Published: November 2023

Ureters are muscular conduits that transport urine from the kidneys to the urinary bladder. During embryonic development, partial or complete duplication of the ureter may result from early splitting of the ureteric bud or the presence of a second ureteric bud. Ureteral duplication is described in approximately 1 in 125 (0.8%) people at autopsy (Nation EF: 1944). Ureteral duplication occurs more frequently in females than in males, which is reported to be approximately 1.6:1. Unilateral duplication is 6 times more common than bilateral duplication. Ureteral duplication is generally associated with ectopia, where one ureter may open in the urethra, vagina, vestibule or epididymal region. Ureterocele is also commonly seen with ureteral duplication. A higher occurrence of uretorenal pathology has been recorded with duplication anomalies. Recognition of the possible effects of abnormal ureteral development is essential in determining the management strategies of the patients with urogenital disorders.We are presenting a case of a middle‐aged Caucasian female cadaver donor with bilateral ureteral duplication. In this case the upper right ureter (25 cm long) drained 3 major calices (~60% of the kidney); the lower right ureter (22 cm long) drained 2 major calices (~40% of the kidney). On the left, both ureters (upper 27cm and lower 25cm long) drained 2 calices each (50% of the kidney). Each set of ureters entered the urinary bladder enclosed in a common fascial sheath and opened separately in the trigone of the urinary bladder. On both sides, the upper ureteric opening was approximately 5 mm below and medial to the lower ureter. On the right side ureteric openings were marked by a prominent intravesicle ureterocele, however no such ureterocele was observed on the left side. No significant enlargement, constriction or polyps were seen in any of the ureters. The size and parenchyma of both kidneys were within normal range from a gross anatomical perspective. The left Kidney (11.2×4.2×3 cm) was larger than the right kidney (9.5×3.8×1.8 cm).There were no sign of renal cysts, hydronephrosis or calculus in either kidney.Urologists taking care of patients need to be aware of this normal variation. Of particular interest are endoscopic procedures, where a ureter that harbors a stone or tumor can be missed, if the normal non‐affected ureter was accessed instead.
Dynamic Surface Temperature Control Prevents Overcooling with N6‐Cyclohexyladenosine in Rats
Authors: Bailey Isaac R , Laughlin Bernard , Moore Lucille A , Bogren Lori K , Barati Zeinab , Drew Kelly L 
Published: November 2023

Cardiac arrest is a leading cause of death in the United States and currently, therapeutic hypothermia, now known as targeted temperature management (TTM), is the only recent treatment modality proven to increase survival rates and reduce morbidity for this condition. Shivering and subsequent metabolic stress however, limits application and benefit of TTM. Stimulating CNS A1 adenosine receptors inhibits shivering and nonshivering thermogenesis in rats and induces a hibernation‐like response in arctic ground squirrels and rats. We found previously that N6‐cyclohexyladenosine (CHA) is more effective at reducing core body temperature (Tb) in dietary restricted (DR) rats than in ad libitum (AL) fed rats. To develop A1AR agonists for TTM in AL fed animals, the current study evaluates the effectiveness of dose, drug and ambient temperature (Ta) on the Tb lowering effects of CHA and capadenoson in freely fed rats. We found that CHA lowered oxygen consumption (VO2) in AL and DR fed rats, consistent with an inhibition of thermogenesis. CHA at 0.5 or 1.0mg/kg in AL rats produced large variations in response at 17.0°C Ta, but after 1.0 mg/kg, IP, all animals cooled to or below a target Tb of 32°C; some animals over‐cooled to as low as 21°C but re‐warmed to 37°C without incident at Ta 23°C. The partial A1AR agonist, capadenoson (1.0 or 2.0mg/kg, IP) produced a consistent response in all animals and decreased Tb to a minimum of 36°C from a mean of 38°C at Ta 17.0°C during the active phase of the circadian cycle. The response to capadenoson was dose‐dependent. To prevent overcooling after CHA we studied continuous IV administration of CHA in combination with dynamic surface temperature control. Results show this approach to be the best at maintaining a desired target Tb. Rigorous optimization of TTM achieved with CHA and dynamic control of conductive cooling will inform future studies aimed at defining the therapeutic benefit of TTM using drugs such as CHA as adjunctive pharmacotherapy.Support or Funding InformationResearch was supported in part by a graduate student fellowship from The Alaska Native Science and Engineering Program to IRB and by NIH R15NS070779, the Alaska Space Grant Program and Alaska INBRE P20GM103395.
Fractional Contribution of UGT2B15 and UGT2B17 in Testosterone Glucuronidation in Human Liver Microsomes and Its Variability
Authors: Zhang Hae Young , Bhatt Deepak Kumar , Prasad Bhagwat 
Published: November 2023

Background and ObjectiveTestosterone has poor and variable oral bioavailability, thus leading to unreliable predictions of its oral pharmacokinetics. Testosterone glucuronidation is the major route of testosterone elimination, and UGT2B15 and UGT2B17 are considered to be the main enzymes responsible. In order to develop a mechanistic physiologically‐based pharmacokinetic (PBPK) model to predict testosterone first‐pass metabolism and its variability, we estimated the fractional contributions of UGT2B15 and UGT2B17 in testosterone hepatic glucuronidation by performing in vitro activity and quantitative proteomic assays in human liver microsomes (HLM) samples genotyped for UGT2B17 deletion.MethodsHLM samples were isolated from 29 individual liver tissues from University of Washington, School of Pharmacy liver bank and quantified for UGT2B15 and UGT2B17 protein expression using a validated trypsin digestion protocol. Glucuronidation activity assay was performed in HLM (0.1 mg/ml total protein) containing 5 mM MgCl2‐100 mM phosphate buffer at pH 7.4, alamethicin (0.1 mg/ml), testosterone (2 nM to 20 μM), and UDPGA (2.5 mM), for 30‐minutes. The reaction was quenched by acetonitrile and the sample centrifuged. The supernatant was analyzed by LC‐MS/MS to quantify testosterone depletion and glucuronide formation. Based on activity‐expression correlation and UGT2B17 genotype information, fractional contribution of UGT2B15 and UGT2B17 in testosterone glucuronidation was established. Further, we expanded our quantification of UGT2B17 to a larger pool (n=446) to examine correlation with age, gender, and genotype.ResultsThe glucuronidation activity was linear for testosterone incubation concentrations ranging from 2 nM to 20 μM. UGT2B17 showed strong protein expression‐activity correlation (r=0.97) while UGT2B15 showed good correlation only in UGT2B17 gene deletion subjects (r=0.72). Fractional contributions of UGT2B17 and UGT2B15 in testosterone glucuronidation were highly variable across individuals, ranging from 0% to 92%, and 8% to 100%, respectively. UGT2B17 protein expression was associated with gender and age (p<0.05).DiscussionWe identified that UGT2B17 is a major contributor in testosterone hepatic glucuronidation in subjects carrying UGT2B17 gene insertion while UGT2B15 protein abundance correlates with the activity in subjects with UGT2B17 gene deletion. We have established methodology to quantitatively characterize individual contributions of each UGT2B isoform in individual HLM samples. Quantification of correlation between UGT2B17 protein abundance and genotype, age, and gender is crucial for developing PBPK model to predict variability in testosterone metabolism. Further, these data will also be critical for predicting outcomes of doping studies and advancing personalized testosterone replacement therapy.Support or Funding InformationDepartment of Pharmaceutics, University of Washington, Seattle, WA
Halogen‐π Interactions in the Cytochrome P450 Active Site: Structural Insights into Human P450 2B6 Substrate Selectivity.
Authors: Shah Manish B , Liu Jingbao , Zhang Qinghai , Stout C. David , Halpert James R 
Published: November 2023

Numerous CYP2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen‐π bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X‐ray crystallography. Bornyl bromide exhibited dual orientations in the active site with the predominant orientation revealing a bromine‐π bond with the Phe‐108 side chain. Bornane demonstrated two orientations with equal occupancy; in both the C2‐atom that bears the bromine in bornyl bromide was displaced by more than 2.5 Å compared with the latter complex. The bromine in myrtenyl bromide π‐bonded with Phe‐297 in CYP2B6, whereas the two major orientations in the active site mutant I114V exhibited bromine‐π interactions with two additional residues, Phe‐108 and Phe‐115. Analysis of existing structures suggests that halogen‐π interactions may be unique to the CYP2B enzymes within CYP family 2 but are also important for CYP3A enzymes.Support or Funding InformationES003619 to Dr. James R. Halpert
Quercetin attenuates Sodium fluoride (NaF)‐induced hypertension through reduction in oxidative stress and heat shock proteins (HSP 70)/extracellular signal regulated kinase (ERK) pathways in rats
Authors: Afolabi Jeremiah Moyinoluwa , Oyagbemi Ademola Adetokunbo , Omobowale Temidayo Olutayo , Asenuga Ebunoluwa Racheal , Ajibade Temitayo Olabisi , Adejumobi Olumuyiwa Abiola , Hassan Fasilat Oluwakemi , Adedapo Adeolu Alex , Yakubu Momoh Audu 
Published: November 2023

Sodium fluoride (NaF), a component of certain household items is known to cause renal, cardiac and DNA damage in animals and man. The present study investigated the effect of co‐administration of quercetin on the toxic effects of NaF in rats. Forty male Wistar rats of 10 per group were used for this study. Group A was the control group which was given water; Group B was exposed to 300 ppm (300 mg/L) of NaF alone in drinking water for a week. Rats in Groups C and D were exposed to 300 ppm (300 mg/L) of NaF in drinking water for a week and co‐administered orally with quercetin at 50 mg/kg and 100 mg/kg, respectively. Electrocardiogram and blood pressure parameters including the systolic pressure, diastolic pressure and mean arterial pressure were measured prior to sacrifice of the rats. Biochemical assays, histology and immunohistochemistry on kidneys and hearts tissues were also carried out. Results reveal a significant (p<0.05) decrease in nitric oxide (NO) of rats that received NaF alone alongside a significant (p<0.05) increase in markers of oxidative stress, hydrogen peroxide (H2O2), malondialdehyde (MDA), advanced oxidative protein products (AOPPs) and serum myeloperoxidase. Systolic, diastolic and mean arterial pressure also increased (p<0.05) significantly in NaF alone treated rats. Genotoxicity results revealed increased frequency of Micronucleated Polychromatic erythrocytes (MnPCEs) in NaF alone treated rats. Furthermore, administration of NaF led to a reduction in the expressions of Heat Shock Proteins (HSP 70) and Extracellular signal regulated kinase ERK. Co‐administration of quercetin (50 mg/kg & 100 mg/kg) with NaF (300 mg/L), however led to reductions in the markers of oxidative stress, blood pressure and frequency of MnPCEs, improved antioxidant defence system and increased expressions of ERK and HSP 70, respectively.Support or Funding InformationThe authors declare that this work was self funded
Manganese Exposure Induces Neuroinflammation by Impairing Mitochondrial Dynamics in Astrocytes
Authors: Malovic Emir , Sarkar Souvarish , Harischandra Dilshan S. , Ngwa Hillary A. , Jin Huajun , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G. 
Published: November 2023

Chronic manganese (Mn) exposure induces neurotoxicity, which is characterized by Parkinsonian symptoms resulting from impairment in the extrapyramidal motor system of the basal ganglia. Mitochondrial dysfunction and oxidative stress are considered key pathophysiological features of Mn neurotoxicity. Recent evidence suggests astrocytes as a major target of Mn neurotoxicity since Mn accumulates predominantly in astrocytes. However, the primary mechanisms underlying Mn‐induced astroglial dysfunction and its role in metal neurotoxicity are not completely understood. In this study, we examined the interrelationship between mitochondrial dysfunction and astrocytic inflammation in Mn neurotoxicity. We first evaluated whether Mn exposure alters mitochondrial bioenergetics in cultured astrocytes. Metabolic activity assessed by MTS assay revealed an IC50 of ~ 100 μM Mn at 24 h in both primary mouse astrocytes (PMAs) and the human astrocytic cell line U373s. Furthermore, Mn treatment reduced mitochondrial mass, indicative of impaired mitochondrial function and biogenesis, which is substantiated by the significant reduction in mRNA of mitofusin‐2, a protein that serves as a ubiquitination target for mitophagy. Seahorse analysis of bioenergetics status in Mn‐treated astrocytes revealed that Mn significantly impaired the basal mitochondrial oxygen consumption rate as well as the ATP‐linked respiration rate. The effect of Mn on mitochondrial energy deficits was further supported by a reduction in ATP production. Mn‐exposed PMAs also exhibited a severe quiescent energy phenotype, which was substantiated by the inability of oligomycin to increase the extracellular acidification rate. Since astrocytes regulate immune functions in CNS, we also evaluated whether Mn modulates astrocytic inflammation. Mn exposure in astrocytes not only stimulated the release of proinflammatory cytokines, but also exacerbated the inflammatory response induced by aggregated α‐synuclein. Lastly, the novel mitochondria‐targeted antioxidant, mito‐apocynin, significantly attenuated Mn‐induced inflammatory gene expression in U373s, further supporting the role of mitochondria dysfunction and oxidative stress in mediating astrogliosis. Collectively, we demonstrate for the first time that Mn drives proinflammatory events in astrocytes by impairing mitochondrial bioenergetics.Support or Funding InformationNIH grants ES026892 and NS088206
Role of Acyl‐CoA Short Chain Synthetase 2 and Acetyl‐CoA in Regulation of Chromatin Modifications and Gene Expression
Authors: Lindahl Anastasia J. , Moffett John R. , Krishnan Jishnu K. S. , Appu Abhilash , Puthillathu Narayanan V. , Krautkramer Kimberly , Dowell James A. , Namboodiri Aryan M. A. , Denu John M. 
Published: November 2023

Post‐translational modifications of proteins control many complex biological processes, including genome expression, chromatin dynamics, metabolism, and cell division. Histone protein acetylation and methylation have been extensively linked to the regulation of chromatin remodeling and gene expression. Chromatin modifying enzymes utilize a variety of metabolites as co‐substrates to catalyze their respective chromatin modifications, closely linking chromatin modifications and metabolism. In this study, we have investigated the role of acyl‐CoA short chain synthetase family member 2 (ACSS2), the cytosolic and nuclear Acetyl‐CoA synthetase of the cell, in the regulation of histone and chromatin protein post‐translational modifications as well as gene expression through proteomic and genomic approaches.Support or Funding InformationAJL was supported by NIH National Research Service Award T32 GM07215
Elucidate the Role of TGF‐beta in Prevention and Treatment of Gingival Hyperplasia Using HGF‐1 Cells
Authors: Kale Vijay , Mathew Sarah , Melnik Mariya , Danh Lisa M 
Published: November 2023

PurposeThe purpose of this study was to evaluate the effects of nifedipine (calcium channel blocker), phenytoin (antiepileptic drug), and losartan (TGF‐beta inhibitor) on cytotoxicity and ATP levels in human gingival fibroblasts (HGF‐1) and evaluate whether losartan attenuates gingival overgrowth caused by nifedipine and phenytoin.MethodsHGF‐1 cells obtained from ATCC were grown to confluency in D‐MEM media supplemented with PenStrep, and bovine serum (FBS 10%) in a CO2 incubator in T‐flasks. For cytotoxicity (LDH leakage in the medium was measured using the CytoTox 96 Non‐radioactive Cytotoxicity Assay Kit) and ATP (Total % ATP was measured using CellTiter‐Glo Luminescent Cell Viability Assay Kit). For ATP and LDH measurements, cells were treated with various concentrations of nifedipine (5, 10, 25, 50 and 100 μM), phenytoin (10, 25, 50, 100 and 200 μM) and losartan (25, 50, 100, 250 and 500 μM) dissolved in DMSO and incubated for 24 h, 72 h and 7 day periods (1×104 cells/well in 96 well plates, 5% CO2, 37 °C and 95% relative humidity).ResultsResults show that none of the drug concentrations had a significant cytotoxic effect on HGF‐1 cells. No significant increase in ATP levels were observed for losartan. At 24h, nifedipine and phenytoin showed significant increase in percent ATP levels when compared to vehicle control. Percent ATP levels for losartan, nifedipine and phenytoin were in range of 101 ± 4 to 113.5 ± 8.2%; 143.1 ± 16.9 to 148.5 ± 20.4% and 135 ± 11.1 to 138.1 ± 16.5% respectively after 24h treatment.ConclusionIn conclusion, our study suggests that nifeidipine and phenytoin causes cell proliferation as evidenced from increased ATP levels. Concentrations identified from these studies will be used to assess effects of losartan on nifedipine and phenytoin induced gingival overgrowth using various markers involved in gingival overgrowth.Support or Funding InformationThis project is supported by College of Pharmacy, Roseman University of Health Sciences, South Jordan, Utah
Chemical Composition and In vitro Antioxidant Activity Evaluation of Acetone Extract of Crinum jagus bulbs (Liliaceae) Linn
Authors: Shorinwa Olusayo Aderonke , Ebong Omotayo Oluranti , Siminialayi Iyeopu Minakiri , Obianime Atuboyedia Wolfe 
Published: November 2023

ObjectiveCrinum jagus is popularly referred to as bush onions in Nigeria and is used for the treatment of various diseases in traditional medicine. Oxidative stress is a central pathogenic factor for chronic diseases. Fruits and vegetables have been shown to exert a protective effect against oxidative stress. The primary nutrients thought to provide the protection afforded by fruit and vegetables are the antioxidant phytochemical agents. Hence, this study investigated the in‐vitro antioxidant potential and chemical composition of the acetone extract of Crinum jagus bulbs.MethodsThe plant extract was screened for the presence of phytochemicals while the antioxidant activity was evaluated with 2, 2‐diphenyl‐1‐picryl‐hydrazyl radical (DPPH) and nitric oxide free radical scavenging assay. Total antioxidant activity, total phenol and total flavonoid content were determined using a spectrophotometer. Isolation and characterization of the active principles were done using GC‐MS techniques.ResultsPreliminary phytochemical screening of the plant revealed the presence of flavonoids, tannins, saponins, steroids and alkaloids. DPPH radical scavenging activity of the plant extract (IC50 value) was found to be 72μg/ml while that of the reference standard, ascorbic acid was 31μg/ml. Nitric oxide scavenging activity of extract was found to be 55μg/ml while that of ascorbic acid was 35μg/ml. The plant extract was found to have a tannin content of 194.1 ± 5.33mg/g (expressed as ascorbic acid equivalent), total flavonoids content (220 ± 0.19mg/g expressed as quercetin acid equivalent), tannin (259.6 ± 0.58mg/g expressed as tannin equivalent) and phenol content of 136.9 ± 0.29 mg/g gallic acid equivalent. The active principles were found to be bowdensine and demethoxybowdensine.ConclusionThe potency of the extract is about 40% (two‐fifth) that of ascorbic acid against DPPH whereas potency of the extract is about 60% (two‐third) that of ascorbic acid for nitric acid inhibition. The findings of this study have shown that the plant possesses good anti‐oxidant activity comparable to the standard.Support or Funding InformationSelf funded
Effect of ultrasound on antimicrobial properties of whey protein‐totarol nanogel
Authors: Guo Mingruo , Ma Shuang 
Published: November 2023

Totarol is a natural antimicrobial compound extracted from the heartwood of the Totara tree. The effects of whey protein‐totarol nanogel treated with ultrasound on the growth of Staphylococcus aureus (S. aureus) were investigated. The particle size of WPI‐Totarol nanogels was reduced by ultrasound treatment from 31.24 ± 5.31 nm to 24.20 ± 4.02 nm and its distribution was also narrowed by the treatment. The data of viscosity and modulus indicated that the flow behaviors of WPI‐Totarol nanogels seemed to be a Newtonian and exerted a typical viscoelastic fluid at protein content of 15% (w/v). Rheological properties were more insensitive to ultrasonic time. Time‐killing assays, agar diffusion tests, the cell membrane damage analysis and microstructure were also exploited to study the antibacterial properties of WPI‐Totarol nanogel. The minimal inhibitory concentration (MIC) of WPI‐Totarol after ultrasound treatment decreased from 4 to 2 μg/mL compared to that without ultrasound treatment. WPI‐Totarol nanogels treated with ultrasound resulted in a significant (P<0.05) decrease in time‐killing after 24 h. The agar diffusion results showed that the inhibition zones of WPI‐Totarol nanogels were 12 and 36 mm for untreated and treated with ultrasound, respectively. The bacterial membrane damages and the microstructure changes also proved that WPI‐Totarol nanogels treated with ultrasound had strong antibacterial activities against S. aureus and the antibacterial effectiveness enhanced with the increasing of ultrasonic time. These findings suggested that WPI‐Totarol nanogels treated with ultrasound were more effective against S. aureus than untreated ones.Support or Funding InformationThe financial support for this project was provided by the Ministry of Science and Technology of China (Project # 2013BAD18B07)
Cardiovascular risk factors and academic performance in Peruvian medical students
Authors: Fernandez‐Rodríguez Lissett Jeanette , Bardales‐Zuta Victor Hugo , Altamirano‐Sarmiento Dan Orlando , Hilario‐Vargas Julio Santos 
Published: November 2023

IntroductionCardiovascular diseases (CVD) are the leading cause of death and disability worldwide. Cardiovascular risk factors are present in increasingly younger populations and medical students are no exception.ObjectivesTo determine if there is a relationship between cardiovascular risk factors and academic performance in medical students enrolled during 2015 at Antenor Orrego Private University (UPAO) in Trujillo, Peru.MethodsA descriptive, cross‐sectional study was performed on a population of 78 second‐year medical students (74% female, mean age of 18.9±1.5 years). Family history of CVD, medical history, tobacco use, vital functions, body mass index, waist – hip index (WHI), serum glycemia levels, electrocardiogram and lipid profile (ATP III) were evaluated. Academic performance was measured using the grade obtained in the morphophysiology I course.ResultsCardiovascular risk factors associated (p<0.05) with poor academic performance were pre‐hypertension in women and men and a WHI > 0.8 in women.ConclusionsCardiovascular risk factors correlate with academic performance of medical students, which underlines the importance of mitigating such risk factors.Support or Funding InformationAntenor Orrego Private University (UPAO)