bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term oral citrulline supplementation in normal rats
Authors: Berthe Marie Clotilde , Breuillard Charlotte , Couderc Remy , Marc Julie , Cynober Luc , Darquy Sylviane 
Published: June 2021

Administration of arginine (Arg) is associated with higher mortality in a clinical trial. The application of citrulline (Cit)as an indirect progenitor for nitric oxide (NO) synthesis is therefore of particular interest. Also, Cit is not a substrate or inducer of arginase, and bypasses the liver metabolism, whereas Arg converted into urea and ornithine (Orn) and is therefore no longer available for endothelial NO synthesisIn this study, we evaluated the effects of a diet with ranging Cit enrichment. Sprague‐Dawley rats (aged 8 weeks) were housed in metabolic cages to monitor food intake, and body weight daily. Every three days blood was sampled at the retro‐orbital sinus to determine glycaemia, insulinemia and amino acids. Rats were given 0.5, 1.0 and 2.0 g Cit/kg body weight mixed into their chow. After 3 weeks they were anaesthetised, decapitated, and blood was collectedResults:Weight (g) increase was not significantly different between the 3 groups (on Day 21: 320±16; 316±19 and 314±8 for the 0.5g, 1 g and 2g Cit groups respectively). A peak of plasma Cit, Arg and Orn (μmol/l) was observed on Day 10. *p<0.005 vs same Cit supplementation at day 0.An increase in glycaemia was observed on Day 21 in all 3 groups; 9.11±0.95, 8.03±0.39 and 9.09±0.40 (mmol/l) in the 0.5g, 1g and 2g Cit groups respectively, without modification to insulinemia:Conclusions:Cit is able to increase plama Arg, so Cit administration can be considered as an alternative to arginine supplementation in clinical use.
Plasma adiponektine relation to inflamatory status of patients with metabolic syndrome
Authors: Lysiak‐Szydlowska Wieslawa , Gnacinska Maria , Magorzewicz Sylwia , Sworczak Krzysztof 
Published: June 2021

Adiponectin is an adipocyte‐specific protein; it plays an important role in the regulation of body weight, insulin resistance and cardiovascular diseases.The aim of the study was to determine relation between plasma concentration of adiponectin and inflammatory status of patients with metabolic syndrome (MS)Methods: The study was performed in 38 obese (+MS) and 17 obese (−MS) patients. Individuals with the metabolic syndrome were identified by the diagnostic criteria of the Intl. Diabetes Fed. Plasma adiponectin, C‐reactive protein (hsCRP), interleukin‐6 (IL‐6), tumor necrosis factor a (TNF a) and insulin concentrations were measured using commercial ELISA kits. HOMA1‐IR was calculated.Results: Adiponectin was significantly lower but IL‐6 and hs‐CRP were higher in patients with metabolic syndrome (Table). The adiponectin levels were inversely correlated with BMI, WHR, % of fat contents, insulin concentration and HOMA‐IR. In the study population, the results indicated that BMI and adiponectin were most closely related to the components of the metabolic syndrome.Conclusion: Adiponectin may be useful parameter to evaluate metabolic syndrome. Research was supported by the Polish Acad. Sci., grants W‐114, W‐751.
Effects of dietary polymethoxylated flavones on glucose metabolism in fructose‐induced insulin resistant hamsters
Authors: Evans Malkanthi , Lloyd Jonathan , Guthrie Najla 
Published: June 2021

Citrus polymethoxylated flavones (PMFs) have been positively implicated in the regulation of sugar, fatty‐acids and lipoprotein metabolism. To evaluate the anti‐diabetic potential of a proprietary formula of PMFs, trademarked Diabetinol™, six male Syrian golden hamsters (Mesocricetus auratus) were fed a 60% fructose diet for 14 days followed by treatment with Diabetinol™ for 42 days. Hamsters in a control group were administered only the 60% fructose control diet for the duration of the study. Treatment group animals showed decreased whole blood glucose and serum insulin levels indicating an improvement in glucose tolerance. The control group showed raised serum insulin levels and impaired glucose tolerance. Total cholesterol and triglyceride levels were also decreased in Diabetinol™ treated animals as compared to fructose‐fed control animals. This study suggests that the PMFs used to formulate Diabetinol™ may have an anti‐diabetic effect and has prompted the pursuit of clinical research into this formulation.Source: KGK Synergize, Inc.
Suppression of growth, progression and metastasis of breast cancer xenografts by dietary complex sphingolipids
Authors: Ding Shengli , Simon Kirk , Schmelz Eva M 
Published: June 2021

Dietary sphingolipids are hydrolyzed in the intestinal tract to bioactive metabolites. In the present study, we investigated if these bioactive can suppress tumor formation, progression and metastasis in distant organs. Human cells representing early, intermediate, late and metastatic stages of breast cancer were injected into the mammary fat pad of nude mice. 0.1% of complex sphingolipids were added to the diet either before or after tumor implant to test both a preventive and an intervention approach. Orally administered sphingolipids affected tumor number and volume in a stage‐dependent manner, with the less aggressive xenografts responding with both lower tumor incidence and tumor volume while the more advanced xenografts responded with a reduction of tumor size only. This appears to correlate with the reduced rate of proliferation that was more affected in xenografts representing earlier stages of breast cancer. However, sphingolipid supplements significantly reduced metastases of MDA‐MB‐231 xenografts to the lungs (60–73%) and bone marrow (60–84%). These results suggest that sphingolipid supplements suppress less aggressive tumors and metastases while they are relatively ineffective against aggressive tumors, indicating a promising potential as chemopreventive agents.Supported by grant BCT0503453 from the Susan G. Komen Foundation and NIH/NCI R03 CA101125.
Effects of diets supplemented with sphingomyelin and Lactobacillus casei and Bifidobacterium bifidum on colon cancer development
Authors: Florencio Marzo , Elena Urdaneta , Jauregui Patricia , Barrenetxe Jaione , Alfaro Maria , Ibañez Francisco , Santidrian Santiago 
Published: June 2021

Functional foods, probiotic and prebiotic, could play a modulating function on colon cancer development. In the present study, we have analysed the possible use of Lactobacillus casei (Lc) and Bifidobacterium bifidum (Bb) (108 ufc/ml) and sphingomyelin (SM) (0.05%), determining its effect on intestinal physiology.Balb/c mice were divided in three groups (n=12) and colon cancer was induced by a dimethilhydrazine injection s.c. for 3 weeks. They were fed for 9 weeks with a control standard diet and milk and standard diet and milk supplemented with the different bacteria strains. Body weight was recorded everyweek. A colon fragment was examined for the presence of aberrant crypt. Jejune was excised and analysed for the expression of SGLT‐1 and PEPT‐1 transporters by western blott. Including Bb/Lc/SM in the diet did affect the final body weight of the animals. In the supplemented diet group the crypt aberrant foci count was smaller (P<0.01) than in other group. SGLT1 expression in the supplemented diet group is significantly higher compared with the cancer colon group and is similar compared with control group. In the expression of PEPT‐1, the supplementation produced a significantly low expression compared with the cancer colon group and it is similar to control group. This data indicate that diets supplemented with symbiotic (Lc, Bb and sphingomyelin) shown beneficial effects related to colon cancer development.
Effect of delayed processing of whole blood on the stability of vitamin B12, folate and transferrin receptor in human serum
Authors: Zhang Mindy , Schleicher Rosemary L , Drammeh Bakary S , Pao Ching‐I , Pfeiffer Christine M 
Published: June 2021

As part of a comprehensive assessment of analyte stability in support of international nutrition studies, we compared several analytical methods that use different principles. Vitamin B12: protein binding (Biorad) and immunoassay (Axsym). Folate: protein binding (Biorad) and microbiological (MA) assay. TfR: immuno‐turbidimetry (Hitachi 912) and ELISA (Ramco). To evaluate stability under harsh field conditions, whole blood (WB) collected from healthy volunteers was stored at 32°C for up to 3 days (d) before serum separation. Specimen treatment effects were calculated using relative changes (%) compared with immediately processed WB. Differences > ± 5% were considered significant.Serum B12 levels (n=27) were unchanged using Axsym; an apparent artifact of incubation of WB at 32°C was measured using the Biorad B12 assay. Significant folate (n=16) losses were measured using either method (greater folate losses with MA versus Biorad). Hitachi serum TfR levels (n=35) were unchanged. Using Ramco, TfR levels were slightly more variable. We conclude that apparent analyte ‘stability’ may be method‐dependent, thus multiple methods should be used to verify findings.
Induction of apoptosis in human chondrosarcoma, synovial sarcoma, liposarcoma and fibrosarcoma cell lines by a novel nutrient mixture
Authors: Roomi M. Waheed , Roomi Nusrath , Ivanov Vadim , Niedzwiecki Aleksandra , Rath Matthias 
Published: June 2021

Sarcomas of soft tissues account for more than 10% of diagnosed cancer in adults. Once the sarcomas have metastasized, current treatment methods are generally ineffective. We have identified a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract that demonstrates a broad spectrum of antitumor activity. We investigated whether the antitumor effect of a NM on sarcoma cell lines was due to apoptosis.Chondrosarcoma (SW‐1353), synovial sarcoma (SW‐982), liposarcoma (SW‐872) and fibrosarcoma (HT‐1080) cell lines (ATCC) were cultured in the recommended media and treated with NM in different doses: 0, 100, 500 and 1000 μg/ml. Cell proliferation was measured by MTT assay, morphology by H&E staining, and apoptosis by Live Green Caspase Detection Kit.The sarcoma cell lines studied showed no toxicity at 100 μg/ml NM, moderate at 500 μg/ml and significant at 1000 μg/ml. When treated with NM at 500 and 1000 μg/ml, obvious apoptotic cells were observed by H&E. The apoptotic cells showed shrinkage with condensed and darkly stained nuclei and strongly acidophilic cytoplasm. Slight apoptosis was observed at 100 μg, moderate at 500 μg/ml and significant at 1000 μg/ml NM for all sarcoma cell lines.The results suggest that NM induces apoptosis in sarcoma cell lines and raises the possibility of its use as a new therapeutic agent.
Molecular characterization of aggressive basal cell carcinoma
Authors: Malliah Rajit , Fernandes Neil , Bhattacharya Sid , Seth Anjali , Chen Wen , Mirani Neena , Hameed Meera , Lambert Clark W. , Fernandes Helen 
Published: June 2021

A subset of Basal Cell Carcinoma (BCC) tumors characterized by rapid growth, recurrence, deep local invasiveness including dura and/or bone is classified as aggressive. These tumors are histologically similar to the non‐aggressive BCC. We have compared molecular signatures of these tumors.21 BCC specimens, 6 aggressive and 15 non‐aggressive were used in the study. DNA was extracted from formalin fixed paraffin embedded sections of 21 pairs of normal and tumor tissue. The specimens were subjected to Loss of Heterozygosity (LOH) analysis in the PATCHED gene using capillary electrophoresis, single nucleotide polymorphisms (SNP's) in cytokine promoter genes by real‐time PCR and melt curve analysis, UV specific mutations in the Sonic Hedgehog (SHH) gene and the V600E mutation in the BRAF kinase gene by sequencing and allele specific Taqman probes.Significant LOH was observed in 54.5% of the aggressive BCC compared to 17.9% of the non‐aggressive BCC. The TNF‐a ‐238 SNP was more prevalent in aggressive (3/6) compared to non‐aggressive BCC (3/12). There was a greater incidence of the IL‐10 ‐1082 SNP ‐ 4/6 in aggressive versus 6/16 in the non‐aggressive BCC. No mutation in the BRAF kinase gene was detected and none of the specimens had mutations in the SHH gene.Our results indicate an increase in LOH in aggressive BCC compared to non‐aggressive specimens and suggest that aggressive BCC prefer a pro‐inflammatory environment.
Expression of Leukemia/Lymphoma Related Factor (LRF) in Human Breast Carcinoma and Comparison with other Cancers
Authors: Agrawal Anshu , Hunter William J. , Silva Edibaldo D. , Mary Davey S. , Murphy Richard F. , Agrawal Devendra K. 
Published: June 2021

Leukemia/lymphoma‐related factor (LRF), a member of the POK family, has a vital function in cellular transformation. Apart from its role in lymphomas, very little is known about its expression in most solid tumors, including breast carcinoma. In this study, LRF mRNA transcripts and protein expression was quantified in benign and malignant breast, colon, liver, lung, renal, and mesothelioma tissues by performing RT‐PCR, Western blot, immunohistochemistry, and immunocytochemistry. All malignant breast tissues expressed significantly more LRF mRNA transcripts and protein than the benign breast tissues. LRF was expressed more strongly in fibroadenoma, invasive lobular carcinoma and ductal carcinoma in situ than in other breast diseases. The ducts in ductal hyperplasia tissues of the breast were weakly positive. In general, a significantly higher expression of LRF was seen in malignant tissue than in the corresponding benign or normal tissue. LRF expression in the carcinoma of the colon, liver, and lung was higher than in the corresponding normal or benign tissues. A strong expression of LRF was observed in normal prostate but not in prostate cancer. These data suggest that LRF could be a marker for malignancy or proliferation of the cancers.(Supported by the Claire Booth Luce Fellowship to A.A.)
Exacerbation of DSS induced intestinal inflammation following inoculation of BALB/c mice with Mycobacterium avium subsp. paratuberculosis
Authors: johnson charles scott , hostetter jesse micheal 
Published: June 2021

Mycobacterium avium subsp. paratuberculosis (M. ptb) DNA has been detected in lesions of human patients with Crohn's disease, a distinct clinical and histologic form of inflammatory bowel disease. However, the significance of this observation remains unresolved. The purpose of the following study was to determine if infection of mice with M. ptb would influence the development of DSS induced intestinal inflammation. BALB/c mice were inoculated intraperitoneally with 1x109 CFU of either live or heat‐killed (HK) M. ptb or saline. At 4–7 months post inoculation, the mice were administered dextran sulfate sodium (DSS) at a suboptimal concentration of 2% in the drinking water for 6 days. After addition of DSS to the drinking water, mouse weights were recorded daily. When the mice were euthanized, sections of small intestine, colon, cecum, liver, and spleen, were collected for histopathology, M. ptb isolation, acid‐fast staining, and for cytokine analysis via qRT‐PCR. Histologic lesion scores were generally more severe and the cecal lengths were generally shorter in the BALB/c mice inoculated with HK M. ptb relative to mice inoculated with live M. ptb or saline. Mice inoculated with either HK or live M. ptb expressed higher levels of IL‐6 and IL‐1 alpha. This data suggests that prior exposure of mice in this model system to M. ptb enhances the colitis that develops after acute exposure to DSS.This study was funded by an Iowa State University research grant.
Human FP prostanoid receptors regulate HIF‐1α through activation of a ROS mediated non‐canonical Wnt signaling pathway
Authors: Chou Chih‐Ling , Xu Wei , Hutchinson Anthony J , Israel Davelene D , Regan John W 
Published: June 2021

Hypoxia inducible factor‐1α (HIF‐1α) is an important transcription factor in the regulation of angiogenesis and is up‐regulated in many cancers. Here, we report that stimulation of the human FP receptor with prostaglandin F2α (PGF2α) activates the non‐canonical Wnt signaling by a mechanism involving the generation of the superoxide anion (O2‐). This activation of non‐canonical Wnt signaling leads to the stabilization of HIF‐1α and stimulation of luciferase reporter gene activity under the control of a hypoxia response element (HRE). Transfection of cells with a dominant negative mutant of T‐cell factor‐4 (TCF‐4) abolishes FP receptor mediated HIF‐1α up‐regulation and stimulation of HRE luciferase activity. These results provide a novel mechanism for the stimulation of angiogenesis under normoxic conditions.Supported by EY011291
Molecular characterization of specific H1‐receptor agonists histaprodifen and its derivates on bovine aortic H1‐receptors
Authors: Carman‐Krzan Marija , Zorko Matjaz , Schunack Walter 
Published: June 2021

We determined the molecular properties of the selective and potent H1‐receptor agonist histaprodifen, its Nα substituted analogues (methyl‐, dimethyl‐, and imidazolylethyl‐ histaprodifen (suprahistaprodifen)) and o′‐, m′‐, p′‐pyridylbutylhistaprodifens. All derivates show high affinity for 3H‐mepyramine labelled bovine aortic H1‐receptor binding sites with the folowing order of potency: suprahistaprodifen >dimethylhistaprodifen >p′‐pyridylbutylhistaprodifen >methylhistaprodifen >m'‐pyridylbutylhistaprodifen >histaprodifen >o′‐pyridylbutylhistaprodifen >histamine. Binding of histaprodifen and all derivates except dimethylhistaprodifen was differentially influenced by the addition of GTP.All drugs, except dimethylhistaprodifen, were activators of G‐proteins. Their order of potency was suprahistaprodifen >histamine >p′‐pyridylbutylhistaprodifen >histaprodifen >m′‐pyridylbutylhistaprodifen >methylhistaprodifen >o′‐ pyridylbutylhistaprodifen. Their effect was abolished by the addition of the H1‐receptor antagonist triprolidine (10μM). Our data suggest that histaprodifens are potent H1‐receptor ligands with diverse effects in our model system. Our results for the histaprodifen and its derivates are in agreement with their agonistic nature, as previously shown in the functional studies, dimethylhistaprodifen behaved as an antagonist in our study.
C‐Type Natriuretic peptide (CNP) release does not contribute to endothelium‐derived hyperpolarizing factor (EDHF) mediated relaxation in porcine coronary artery
Authors: Ng Kwok Fu Jacobus , Leung Susan Wai Sum , Man Ricky Ying Keung , Vanhoutte Paul M 
Published: June 2021

Objective: The release of CNP accounts for EDHF‐mediated relaxations in the rat mesenteric artery1 and is Gi protein dependent2. EDHF‐mediated relaxations in the porcine coronary artery are not Gi dependent3. This study investigates whether or not CNP release accounts for EDHF‐responses in this artery.Methods: (1) CNP concentration was measured by enzyme immunoassay in bathing solution containing porcine coronary arterial rings where EDHF response was initiated by bradykinin (100 nM). (2) EDHF‐mediated relaxations induced by SFLLRN were compared with those to exogenous CNP in the presence of phosphoramidon (10 μM; known to potentiate CNP induced relaxations).Results: There was no significant difference in the CNP concentrations between chambers containing rings that did or did not exhibit a EDHF‐mediated response. Relaxations induced by CNP alone were potentiated by phosphoramidon (maximal relaxation 60.7 ± 7.7 % vs 84.1 ± 7.5 %, control vs phosphoramidon, P<0.05) but the EDHF‐mediated responses to SFLLRN were not (maximal relaxation 69.9 ± 9.1 % vs 72.8 ± 9.9 %, control vs phosphoramidon)Conclusions: Unlike in the mesenteric artery and the heart of the rat, CNP release does not contribute to EDHF‐mediated relaxations in the porcine coronary artery.
Agonist‐induced desensitization of rat bladder relaxation by β‐adrenergic agonists
Authors: Vrydag Wim , Michel Martin C. 
Published: June 2021

The overactive bladder symptom complex has a high prevalence and reduces quality of life. A potential drug target is the β‐adrenergic receptor, which mediates the detrusor smooth muscle relaxation. Since treatment with β‐adrenergic receptor agonists is symptomatic only, it requires a long term usage and could be limited by desensitization of the receptor. Therefore, we have explored the presence and possible mechanisms of such desensitization in the bladder.Rat bladder strips were studied in an organ bath after 6 hours pre‐stimulation with isoproterenol, forskolin or vehicle. Following wash‐out relaxation curves were generated against both KCl‐induced tone and passive tension.A 6 hour pre‐stimulation with isoproterenol desensitized the subsequent relaxation in response to isoproterenol against both KCl and passive tension, but not that to forskolin. In contrast, pre‐stimulation with forskolin did not alter the efficacy or potency of isoproterenol.We conclude that rat bladder β‐adrenergic receptors are subject to agonist‐induced desensitization despite a proposed involvement of the relatively desensitization‐resistant β3‐subtype. Whether this also occurs with agonists currently in clinical development for the treatment of bladder dysfunction, remains to be established.
Genotype‐phenotype correlations for polymorphisms in cytochrome b5 and NADH cytochrome b5 reductase and hepatic sulfamethoxazole hydroxylamine reduction
Authors: Sacco James C , Trepanier Lauren A 
Published: June 2021

NADH cytochrome b5 reductase (b5R) and cytochrome b5 (b5) catalyze the reduction of sulfamethoxazole hydroxylamine (SMX‐HA) to the parent drug sulfamethoxazole. SMX‐HA and a spontaneous nitroso metabolite are thought to contribute to sulfonamide hypersensitivity. Variability in SMX‐HA reduction could therefore contribute to the risk of sulfonamide hypersensitivity. The aim of this study was to characterize variability in SMX‐HA reduction in 100 human livers, and determine genotype‐phenotype correlations for polymorphisms in b5R and b5 cDNA. Mean SMX‐HA reduction (200 μM) was 0.59 ± 0.33 nmol/min/mg protein, with a 10‐fold range (0.11–1.23) in 70 livers to date. Vmax for livers with high reduction activity was an order of magnitude higher than livers with low reduction activity.Three individuals were heterozygous for novel single‐nucleotide polymorphisms (SNPs) in either b5R (R59H, R297H) or b5 (S5A). The subject heterozygous for the R297H had low reductase activity (0.21 nmol/min/mg). Two previously reported synonymous b5 SNPs (C35T and G288A; frequencies: 27% and 29% in this population) were found to be in linkage disequilibrium. Work is ongoing to determine the relationship between non‐synonymous SNPs in b5R or b5 and outlier reduction activities.
Regulation of ATP‐binding cassette (Abc) transporters by organoselenium compounds
Authors: Arch Dorinda D , El‐Sayed Wael M , Aboul‐Fadl Tarek , Roberts Jeannette C , Franklin Michael R 
Published: June 2021

Selenium‐containing compounds have demonstrated chemopreventive activity in a variety of chemically‐induced tumor models, but a unifying mechanism for this effect remains elusive. Altered disposition of chemicals and toxic metabolites may be contributing factors. Following dietary ingestion of selenocysteine pro‐drugs and selenocystine (15 ppm Se) for 1 month, mouse hepatic glutathione transferase, quinone oxidoreductase and microsomal epoxide hydrolase activities were elevated by 2‐butyl‐ and 2‐oxoselenazolidine‐4‐carboxylic acids (SCAs) and selenocystine, but not by 2‐cyclohexyl‐, 2‐phenyl‐, and 2‐(2′‐hydroxyphenyl)‐ SCAs. Expression of multidrug resistance‐associated proteins and other Abc transporters were evaluated by qPCR. Of 10 transporters examined, none responded in a pattern similar to the activities of the enzymes capable of being regulated via the Nrf2/ARE mechanism. Abcc3 (Mrp3) was increased only by 2‐butylSCA and no transporters were induced by 2‐oxoSCA or selenocystine. 2‐(2′‐Hydroxyphenyl)SCA was the only compound that induced expression of Abcc2 (Mrp2) and Abcb6. All the selenocompounds reduced the expression of Abcb11. Expression of Abcc1, Abcc4, Abcc5, Abcc6, and Abcg2 and Abca3, was not altered by any compound. Selenocompound regulation of Abc transporter expression appears to be compound dependent and unrelated to the Nrf2/ARE pathway.Support: GM 058913