Effect of l-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo

1992 ◽  
Vol 83 (2) ◽  
pp. 183-190 ◽  
Author(s):  
P. C. Dagnelie ◽  
D. K. Menon ◽  
I. J. Cox ◽  
J. D. Bell ◽  
J. Sargentoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Human Liver ◽  
Pulse Sequence ◽  
Whole Body ◽  
Maximal Increase ◽  
Normal Human Liver ◽  
Normal Human ◽  
Biochemical Pathology

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters]. 5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.

Ru(III) complexes of pyrazolopyrimidines as anticancer agents: In vitro, in vivo anticancer activity and underlying multi-mechanisms

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Wen-Ying Shen ◽  
Qi-Yuan Yang ◽  
Zhen-Feng Chen ◽  
Hong Liang
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human ◽  
Low Toxicity

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(Ln)(H2O)Cl3] (13, n=13) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver...

scholarly journals In Vivo Radioprotective Activity of Cell-Permeable Bifunctional Antioxidant Enzyme GST-TAT-SOD against Whole-Body Ionizing Irradiation in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jianru Pan ◽  
Huocong He ◽  
Ying Su ◽  
Guangjin Zheng ◽  
Junxin Wu ◽  
...  
Keyword(s):  
Growth Rate ◽  
Antioxidant Activity ◽  
Body Weight ◽  
Whole Body ◽  
White Pulp ◽  
Radioprotective Activity ◽  
Significant Difference ◽  
Wbc Count

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.

In vivo n.m.r. imaging in medicine: the Aberdeen approach, both physical and biological

1980 ◽  
Vol 289 (1037) ◽  
pp. 519-533 ◽  
Keyword(s):  
Pulse Sequence ◽  
The Body ◽  
Spin Lattice Relaxation ◽  
Surrounding Tissue ◽  
Whole Body ◽  
Spin Concentration ◽  
Stage Of Development ◽  
Wide Range

A novel magnetic field and radio frequency (1.7 MHz) pulse sequence is described for a whole body n.m.r. imaging machine under construction. Selective excitation is used to obtain signals from successive lines of proton spins (water) across the body to build up an image of a transverse section. The images display spin concentration and spin-lattice relaxation time, T 1 , separately. For a 50 % change in T 1 to be discerned in the human trunk, a spatial resolution of 2 cm 3 is expected for a 2 min scan and 0.5 cm 3 for a 30 min scan. Very preliminary images at the present incomplete stage of development show the geometrical accuracy and T 1 discrimination: an in vivo image demonstrates some of the difficulties to be overcome. In vitro measurements of normal rabbit tissue samples have been made at 24 MHz to map the T 1 distributions that can be expected from normal subjects. The transposition of this information from rabbit to man, and from 24 MHz to 2.5 MHz have been checked and the comparison shown to be meaningful. Of pathological samples, human breast tumour and human liver metastases offer a good contrast to their surrounding tissue, and an experimental investigation has shown that tissue immediately surrounding a tumour also has an elevated T 1 value. A wide range of abnormalities that are associated with abnormal fluid formation in the body may be amenable to imaging by the n.m.r. technique. Potential hazards are believed to be small in the present generation of equipment.

Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

2021 ◽  
Vol 76 (3-4) ◽  
pp. 201-210
Author(s):  
Nabeel A. Abdul-Ridha ◽  
Afraah D. Salmaan ◽  
Rita Sabah ◽  
Bahjat Saeed ◽  
Najim A. Al-Masoudi
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Hydrophobic Interactions ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Protein Receptor ◽  
Normal Human Liver ◽  
Normal Human

Abstract The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.

scholarly journals Clinical Evaluation of Efficacy of99mTC -Ethambutol in Tubercular Lesion Imaging

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Namrata Singh ◽  
A. Bhatnagar
Keyword(s):  
Clinical Trial ◽  
Human Subjects ◽  
Animal Experiments ◽  
Whole Body ◽  
Biodistribution Studies ◽  
Biological Studies ◽  
Normal Human ◽  
Tubercular Lesion

Purpose. The aim of this work was to develop specific radiopharmaceutical and to evaluate its efficacy in human to detect and locate the tubercular lesion.Materials and Methods.99mTc-Ethambutol (EMB) was produced by direct labeling method.In vitro and in vivobiological studies and animal experiments were done. Phase I Clinical trial was performed. As per plan, 2 normal human subjects for biodistribution studies and fourteen patients (8 males and 6 females; age range of 25–50, with one patient aged 12 years as an exception) were chosen for clinical trial. Whole body scan and spots were acquired at 1 hour and 4 hour. Angiography, blood pool, and 24-hours spot images of the infected areas were also acquired.Result. Radiolabeling yielded>85%of labeled complex.In vitro and in vivobiological studies and animal experiments indicated99mTc-EMB as a specific tuberculosis imaging agent. The biodistribution study in normal human subjects suggested stability of99mTc-EMB, with main excretory pathways being renal and hepatobiliary, which appeared to be similar to the known behavior of unlabeled EMB. No adverse reactions were observed.99mTc-EMB got localized in pulmonary and bone tubercular lesions. Scintigrams of99mTc-EMB and99mTc-Ciprofloxacin were compared at different time intervals.Conclusion. The present study states that developed99mTc-EMB has high potential to qualify as a specific tuberculosis imaging radiopharmaceutical and is safe for human use.

scholarly journals Methodological approaches to assess body-weight regulation and aetiology of obesity

2000 ◽  
Vol 59 (3) ◽  
pp. 405-411 ◽  
Author(s):  
Amelia Marti ◽  
Carlos De Miguel ◽  
Susan A Jebb ◽  
Max Lafontan ◽  
Martine Laville ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Laboratory Animals ◽  
Positive Energy ◽  
Weight Regulation ◽  
Body Weight Regulation

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Presence and Possible Origin of ɛ(γ-Glutamyl)Lysine Isodipeptide in Human Plasma

1992 ◽  
Vol 67 (01) ◽  
pp. 060-062 ◽  
Author(s):  
J Harsfalvi ◽  
E Tarcsa ◽  
M Udvardy ◽  
G Zajka ◽  
T Szarvas ◽  
...  
Keyword(s):  
Human Plasma ◽  
Fibrinolytic Therapy ◽  
Normal Human Plasma ◽  
Normal Human ◽  
Hplc Technique ◽  
Significant Change

Summaryɛ(γ-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 μmol/1. Incubation of in vitro clotted plasma at 37° C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.

Evaluation of a New Preparation of Urokinase

1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol
Keyword(s):  
Body Weight ◽  
Maintenance Therapy ◽  
Initial Dose ◽  
Fibrinolytic Activity ◽  
Pharmacological Effect ◽  
Whole Body ◽  
Fibrinolytic Agent ◽  
Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

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