Effects of Semistarvation on the Distribution of Erythrocytes and Plasma in Organs and Tissues of the Rat

Lasher, Earl P.; Simmons, Barbara S.; Everett, N. B.

doi:10.1093/jn/65.2.317

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…This does not appear to have been reported before in rats, but is consistent with the prior observation that a 48-h food deprivation did result in a 9% increase in hematocrit in lactating goats (Chaiyabutr et al, 1980). It is also consistent with the previously documented observation of decreased plasma volume with food deprivation in rats despite ad libitum access to water (Lasher et al, 1958;Wright and O'Kelly, 1973).…”

Section: Discussionsupporting

confidence: 93%

Coordination of mammary metabolism and blood flow after refeeding in rats

Stewart

Cooper

Davis³

2009

Journal of Dairy Science

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The production of milk is closely linked to nutritional state in many mammalian species, but the mechanisms by which changes in nutritional state are signaled to the mammary glands are poorly understood. Simultaneous measurements of mammary blood flow and glucose arterio-venous difference were made across the inguinal mammary glands of anesthetized, lactating rats. Blood flow to the mammary glands of previously fed rats was 0.48 mL/min per gram of mammary tissue. Glucose supply was 1.7 mumol/min per gram and 28% was extracted by the mammary glands. After food deprivation for 18 h, mammary blood flow decreased 48%, glucose arterio-venous difference decreased 72%, and hematocrit increased 7%, resulting in a 60% decrease in glucose supply and an 88% decrease in glucose uptake. After 1 h of refeeding, glucose supply had returned to a similar level to that of normally fed animals, but glucose uptake was 60% higher than in the normally fed state. Mammary glucose uptake was not closely linked to either blood flow or glucose supply, suggesting that substrate supply was not the primary determinant of mammary metabolism. Denervation experiments showed that the mammary metabolic response to altered nutritional state was also unlikely to be closely controlled by neural pathways. Severance of the cutaneous branch of the posterior division of the femoral nerve innervating the inguinal mammary glands did not reduce the high glucose uptake by mammary glands of either fed or refed rats, nor did denervation change the low glucose uptake by mammary glands of food-deprived rats. Denervation reduced blood flow in the associated mammary gland, however, indicating that neural pathways may play a role in supporting mammary blood flow when food is available. In in vitro experiments, the rate of glucose uptake was 35% lower in mammary acini from food-deprived rats than in fed rats 2.5 h after tissue removal, indicating some persistence of the food deprivation-induced suppression of mammary metabolism. Administration of insulin increased glucose uptake in acini from both fed and food-deprived rats, indicating that insulin may be involved in signaling the mammary gland of the restoration of nutrient supply when food-deprived rats are refed. The effects of administration of a gut extract in vivo and in vitro are discussed.

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Section: Discussionsupporting

confidence: 93%

Coordination of mammary metabolism and blood flow after refeeding in rats

Stewart

Cooper

Davis³

2009

Journal of Dairy Science

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“…A few rats ( n = 4) were euthanized with focused microwave irradiation and the brain tissue (i.e., normal and tumor) was removed, weighed and homogenized for agent concentration analysis ex vivo by 1 H NMR. Blood plasma samples were also collected to measure the agent in the plasma for correction of agent concentration in the tissue using tissue‐plasma volumes . NMR solutions of each organ suspensions were prepared and 0.1 mM TmDOTMA − was used as an internal reference.…”

Section: Methodsmentioning

confidence: 99%

Imaging the intratumoral–peritumoral extracellular pH gradient of gliomas

et al. 2016

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Solid tumors have acidic extracellular pH (pHe) but near neutral intracellular pH (pHi). Because acidic pHe milieu is conducive to tumor growth and builds resistance to therapy, simultaneous mapping of pHe inside and outside the tumor (i.e., intratumoral-peritumoral pHe gradient) fulfills an important need in cancer imaging. We used Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), which utilizes shifts of nonexchangeable protons from macrocyclic chelates (e.g., 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) or DOTP8−) complexed with paramagnetic thulium (Tm3+) ion, to generate in vivo pHe maps in rat brains bearing 9L and RG2 tumors. Upon TmDOTP5− infusion, MRI identified the tumor boundary by enhanced water transverse relaxation and BIRDS allowed imaging of intratumoral-peritumoral pHe gradients. The pHe measured by BIRDS was compared with pHi measured with 31P-MRS. In normal tissue pHe was similar to pHi, but inside the tumor pHe was lower than pHi. While the intratumoral pHe was acidic for both tumor types, peritumoral pHe varied with tumor type. The intratumoral-peritumoral pHe gradient was much larger for 9L than RG2 tumors, because in RG2 tumors acidic pHe was found in distal peritumoral regions. Increased presence of Ki-67 positive cells beyond the RG2 tumor border suggested that RG2 was more invasive than 9L tumor. These results indicate that extensive acidic pHe beyond the tumor boundary correlates with tumor cell invasion. In summary, BIRDS has sensitivity to map in vivo intratumoral-peritumoral pHe gradient, thereby creating preclinical applications in monitoring cancer therapeutic responses (e.g., with pHe-altering drugs).

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“…Blood plasma and urine samples were collected throughout the experiment from rats in Groups I and II. Plasma concentrations were used for calibrating the agent concentration in the tissue using tissue–plasma volumes . After the infusion, rats were euthanized with focused microwave irradiation , immediately after which various organs (i.e.…”

Section: Methodsmentioning

confidence: 99%

Towards longitudinal mapping of extracellular pH in gliomas

et al. 2016

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Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), an ultrafast chemical shift imaging technique, requires infusion of paramagnetic probes like 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (DOTP8−) complexed with thulium (Tm3+) ion (i.e., TmDOTP5−), where the pH-sensitive resonances of hyperfine-shifted nonexchangeable protons contained within the paramagnetic magnetic resonance probe are detected. While imaging extracellular pH (pHe) with BIRDS meets an important cancer research need by mapping the intratumoral-peritumoral pHe gradient, the surgical intervention used to raise the probe’s plasma concentration limits longitudinal scans on the same subject. Here we describe using probenecid (i.e., an organic anion transporter inhibitor) to temporarily restrict renal clearance of TmDOTP5−, thereby facilitating molecular imaging by BIRDS without surgical intervention. Co-infusion of probenecid with TmDOTP5− increased the probe’s distribution into various organs, including the brain, compared with when infusing TmDOTP5− alone. In vivo BIRDS data using probenecid/TmDOTP5− co-infusion method in rats bearing RG2, 9L, and U87 brain tumors showed intratumoral-peritumoral pHe gradients that were unaffected by the probe dose. This co-infusion method can be used for pHe mapping with BIRDS in preclinical models for tumor characterization and therapeutic monitoring given the possibility of repeated scans with BIRDS (e.g., over days and even weeks) in the same subject. The longitudinal pHe readout by probenecid/TmDOTP5− co-infusion method for BIRDS adds translational value in tumor assessment and treatment.

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Effects of Semistarvation on the Distribution of Erythrocytes and Plasma in Organs and Tissues of the Rat

Cited by 3 publications

References 4 publications

Coordination of mammary metabolism and blood flow after refeeding in rats

Coordination of mammary metabolism and blood flow after refeeding in rats

Imaging the intratumoral–peritumoral extracellular pH gradient of gliomas

Towards longitudinal mapping of extracellular pH in gliomas

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