Growth-related changes of phosphorus metabolites in VX-2 carcinoma implanted into rabbit thigh muscle: in vivo 31P MR spectroscopy

2016 ◽  
Author(s):  
Hyeong-Kil Kim ◽  
Gwang Woo Jeong ◽  
Tae-Hoon Kim ◽  
Gwang-Won Kim ◽  
Jong-Bong Kim
Keyword(s):  
Tumor Growth ◽  
Intracellular Ph ◽  
Tumor Necrosis ◽  
Time Course ◽  
Ph Value ◽  
Thigh Muscle ◽  
Ph Values ◽  
Concentration Changes ◽  
Phosphorus Metabolites

The purpose of this study was to evaluate the usefulness of in vivo 31P magnetic resonance spectroscopy (MRS) for monitoring changes in growth-related phosphate metabolite concentration and intracellular pH value in rabbit thigh muscle implanted with VX-2 carcinoma. The time-course magnetic resonance imaging (MRI) and in vivo 31P MRS were examined weekly in the course of 10 weeks following the onset of a VX-2 carcinoma implantation. The spectra were quantitatively analyzed to obtain vital information on the time course variation of the phosphorus metabolites and intracellular pH value according to the tumor growth. Elevation in the concentrations of phosphormonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) was observed over the time course of 3-4 weeks after the implantation of VX2 carcinoma, while the rest of the metabolites, PCr and ATP tended to be constant. The concentration changes of PME, Pi, and PDE were positively correlated with the volumes of tumor necrosis. The intracellular pH values decreased with the time course of tumor growth and the volumes of tumor necrosis. In vivo 31P MRS is capable of non-invasive monitoring of intracellular pH values as well as the concentration changes of phosphate metabolites during tumor growth.

scholarly journals Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

2020 ◽  
Vol 21 (7) ◽  
pp. 2513 ◽  
Author(s):  
Julia C. Berkmann ◽  
Aaron X. Herrera Martin ◽  
Agnes Ellinghaus ◽  
Claudia Schlundt ◽  
Hanna Schell ◽  
...  
Keyword(s):  
Individual Differences ◽  
Animal Models ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Controlled Drug Release ◽  
Post Injury ◽  
Ph Changes ◽  
Ph Values ◽  
Local Ph

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.

scholarly journals Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of(RGD)3-tTF

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng-jie Huang ◽  
Yilin Zhao ◽  
Wei-yuan Luo ◽  
Jun You ◽  
Shui-wen Li ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Necrosis ◽  
Protein Targeting ◽  
Clotting Time ◽  
Coagulation Activity ◽  
Promising Strategy ◽  
Volume Blood ◽  
Vessel Thrombosis

Purpose. Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrinαvβ3and tTF induce blood coagulation in tumor vessels.Methods. The bioactivities of (RGD)3-tTF including coagulation activity,FXactivation, and binding with integrinαvβ3were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated.Results. The clotting time andFXactivation of (RGD)3-tTF were similar to that of TF (P>0.05) but different with that of RGD (P<0.05). (RGD)3-tTF presented a higher binding withαvβ3than that of RGD and TF at the concentration of 0.2 μmol/L (P<0.05). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (P<0.05).Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.

scholarly journals The role of pH values in porcine reproductive tracts of male and female individuals

2008 ◽  
Vol 24 (3-4) ◽  
pp. 101-108 ◽  
Author(s):  
T. Smiljakovic ◽  
S. Josipovic ◽  
O. Kosovac ◽  
N. Delic ◽  
S. Aleksic ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Ph Value ◽  
Rete Testis ◽  
Female Reproductive Tract ◽  
Ductus Deferens ◽  
Male And Female ◽  
Ph Values ◽  
Small Peak

For a long time, in practice, and science, has been known that pH values of sperm and vagina are important for successful fertilization. In this investigation this fact was confirmed, and the goal was to investigate the role of pH values through whole reproductive tract of male and female individuals: testis, rete testis, epididymis, ductus deferens, Cowper's gland, vesicula seminalis, prostata, corpus cavernosus, corpus spongiosus, epitel tissue of penis tube, sperm, vagina, uterus, horn of uterus, oviduct, fimbrie ovarica, ovarium, follicular fluid. Measurement was performed in reproductive active males as well as before and after ovulation in females. Porcine reproductive tracts (per 15 female and male individuals) were collected from institute's slaughterhouse, immediately post mortem dissected, homogenised and pH values were measured (according to method Rede&Rahelic (1969)). Ovarium and follicular liquid have the highest pH values (7,4) in females, but a small peak in preovulatory oviduct is also present and corresponded to pH of sperm of reproductive fully active male individuals (pH=app.7,2). After fertilization pH in surrounding of zygot (through depolarisation of its membrane) in oviduct, and zygot which then has external decreased pH value moves to less pH values regions by the same principle, that means to uterus, (pH between 7,2 (horn) and 7,07(cervix)) in postovulatory female reproductive tract, where nidation of blastocyst occurs. This investigation could help to elucidate knowledge about reproductive physiology in vivo, giving importance to role of pH values along reproductive tract of male and female individuals.

Messungen zur Manipulation der Glucose-abhängigen Tumorsäuerung in vivo

1968 ◽  
Vol 23 (11) ◽  
pp. 1461-1475 ◽  
Author(s):  
Hermann Matthias Rauen ◽  
Michael Friedrich ◽  
Klaus Norpoth
Keyword(s):  
Ph Value ◽  
Alkylating Agents ◽  
Lactate Concentration ◽  
Ph Values ◽  
Tumor Lesion ◽  
Wet Weight ◽  
Glass Electrodes ◽  
Rat Tumors

On experimental rat tumors, preferentially on DS-Carcinosarcoma, special glass electrodes were used to measure and to register development of tissue-pH after injection of glucose into the rats.On tumor surface pH-values were lowered more quickly and increased much faster as in tumor depth. The lowest registered pH was about 5,9.High s. c. dosages of Insulin caused a marked decrease of pH-values for nearly one hour too. In metabole effective small tumors tumor acidity could be regulated satisfactory with administered glucose and insulin between pH 7,0 and 6,0.Determination of lactate concentration in tumor tissue, surrounding the electrode, indicated a linear correlation between pH-value und lactate concentration in the range between pH 6,0 and 7,0. Regression coefficient comes to — 40,9 ± 2,2 ×10-3 mMol/g wet weight and pH-unit.It is emphasized that according to the varying cell supply the compact tumor shows no homogeneity on pH-rates, acidification kinetics, and sensibility against acidotic cell lesion.Results are criticized with reference to other publications and their significance for the theory of tumor lesion by alkylating agents is discussed.

scholarly journals Functional White-Laser Imaging to Study Brain Oxygen Uncoupling/Recoupling in Songbirds

2010 ◽  
Vol 31 (2) ◽  
pp. 393-400 ◽  
Author(s):  
Stéphane Mottin ◽  
Bruno Montcel ◽  
Hugues Guillet de Chatellus ◽  
Stéphane Ramstein
Keyword(s):  
Time Course ◽  
Brain Aging ◽  
Optical Tomography ◽  
Blood Oxygen Level Dependent ◽  
Blood Oxygen ◽  
Blood Oxygen Level ◽  
Subsequent Increase ◽  
Brain Oxygen ◽  
Concentration Changes

Contrary to the intense debate about brain oxygen dynamics and its uncoupling in mammals, very little is known in birds. In zebra finches, picosecond optical tomography with a white laser and a streak camera can measure in vivo oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) concentration changes following physiologic stimulation (familiar calls and songs). Picosecond optical tomography showed sufficient submicromolar sensitivity to resolve the fast changes in the hippocampus and auditory forebrain areas with 250 μm resolution. The time course is composed of (1) an early 2-second-long event with a significant decrease in Hb and HbO2 levels of −0.7 and −0.9 μmol/L, respectively, (2) a subsequent increase in blood oxygen availability with a plateau of HbO2 (+ 0.3 μmol/L), and (3) pronounced vasodilatation events immediately after the end of the stimulus. One of the findings of our study is the direct link between blood oxygen level-dependent signals previously published in birds and our results. Furthermore, the early vasoconstriction event and poststimulus ringing seem to be more pronounced in birds than in mammals. These results in birds, tachymetabolic vertebrates with a long lifespan, can potentially yield new insights, e.g., into brain aging.

Na+/H+ and HCO3−/Cl− exchange in the control of intracellular pH in vivo in the spontaneously hypertensive rat

1991 ◽  
Vol 81 (6) ◽  
pp. 743-750 ◽  
Author(s):  
P. D. Syme ◽  
J. K. Aronson ◽  
C. H. Thompson ◽  
E. M. Williams ◽  
Y. Green ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Ph ◽  
Acid Concentration ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Concentration Changes ◽  
Wistar Kyoto

1. We have previously shown that the cytosolic acid concentration changes in skeletal muscle during contraction in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats in vivo. We have now found that this change was unaffected by 20% inhaled CO2 or by 4,4′-di-isothiocyanostilbene-2,2′-disulphonate. This is evidence that HCO3− exchange in vivo is not important in the control of cytosolic acid concentration during skeletal muscle contraction in either spontaneously hypertensive or Wistar-Kyoto rats. 2. We have also previously shown that the difference in cytosolic acid response during contraction between spontaneously hypertensive and Wistar-Kyoto rats is due to increased Na+/H+ antiporter activity in the spontaneously hypertensive rats. Our current findings suggest that this increase in Na+/H+ antiporter activity is more likely to be due to a change in the Km of the antiporter than to a change in the Vmax. We estimate that the Km of the antiporter changes in hypertension from pH 7.16 to 7.33. 3. We did not find any differences between adult spontaneously hypertensive and Wistar-Kyoto rats with regard to resting intracellular and extracellular pH and resting intracellular and extracellular HCO3− concentrations. In addition, we did not find any evidence of a difference in skeletal muscle HCO3−/Cl− exchange between adult spontaneously hypertensive and Wistar-Kyoto rats. 4. At rest, skeletal muscles of the spontaneously hypertensive and Wistar-Kyoto rats have the same lactate production, HCO3−/Cl− exchange and arterial partial pressure of CO2. In addition, we can also calculate that at a resting intracellular pH of 7.05 in the spontaneously hypertensive rats, the antiporter is 66% saturated. The corresponding value in the Wistar-Kyoto rats (resting intracellular pH 7.04) is 57%. This explains the lack of difference in resting intracellular pH between the two strains of rat and suggests that at rest differences in Na+/H+ antiporter activity due to a shift in Km of the antiporter are too small to result in a difference in resting pH. 5. Furthermore, Na+/H+ antiporter activity around pH 7.0 was unable to prevent the acidosis caused by CO2 loading. Thus resting pH in skeletal muscle in vivo is determined largely by the HCO3− system and in this regard skeletal muscle is similar to vascular smooth muscle.

scholarly journals Studies on the Regulation of Enzyme Binding During Anoxia in Isolated Tissues of Busycon Canaliculatum

1991 ◽  
Vol 156 (1) ◽  
pp. 467-481
Author(s):  
STEPHEN P. J. BROOKS ◽  
KENNETH B. STOREY
Keyword(s):  
Particulate Matter ◽  
Protein Kinase ◽  
Intracellular Ph ◽  
Anoxic Conditions ◽  
Enzyme Binding ◽  
Busycon Canaliculatum ◽  
Ph Values ◽  
Isolated Ventricle

The role of pH and protein kinase second messengers in triggering or potentiating anoxia-linked changes in enzyme binding to particulate matter were evaluated using in vitro incubations of isolated ventricle strips of Busycon canaliculatum (L.) (Prosobranchia, Melongenidae). Incubating whelks under anoxic conditions for 4h reduced the percentage of phosphofructokinase (PFK), aldolase, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase (PK) activity associated with cellular particulate matter. Triose phosphate isomerase, phosphoglycerate kinase, phosphoglyceromutase and enolase showed no changes in enzyme binding when whelks were subjected to anoxic stress in vivo. Incubating isolated ventricle strips in vitro under anoxic conditions simulated the changes seen in vivo in whole, anoxic whelks with respect to the percentage of PFK and PK bound during anoxic stress; both whole-animal studies and isolated tissue studies showed reduced PFK and PK binding after 4 h of anoxic incubation. Tissue pH could be artificially changed by incubating isolated ventricle strips in sea water buffered to a desired pH. This permitted an investigation of the effect of intracellular pH on PFK and PK binding in situ. PFK and PK responded to altered intracellular pH with increased enzyme binding at lower intracellular pH values and decreased enzyme binding at higher intracellular pH values. These binding patterns were exactly the opposite of those observed during anoxia; during anoxia stress, both intracellular pH and the percentage of PFK and PK associated with particulate matter decreased. Addition of the second messenger compounds dibutyryl cyclic AMP, dibutyryl cyclic GMP or phorbol 12-myristate 13-acetate plus the calcium ionophore A23187 had no effect on the percentage of activity bound to subcellular structures measured under either normoxic or anoxic conditions. This study suggests that enzyme binding in vivo is not regulated by changes in intracellular pH or concentrations of protein kinase second messenger compounds during anoxia.

Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics

1993 ◽  
Vol 265 (2) ◽  
pp. C365-C374 ◽  
Author(s):  
J. M. Wan ◽  
F. Fogt ◽  
B. R. Bistrian ◽  
N. W. Istfan
Keyword(s):  
Cell Cycle ◽  
Tumor Necrosis Factor ◽  
Tumor Growth ◽  
Protein Metabolism ◽  
Tumor Necrosis ◽  
Compensatory Mechanism ◽  
Protein Breakdown ◽  
Cell Cycle Kinetics ◽  
Necrosis Factor

To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.

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