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T Glonek

Publications and source records attributed to T Glonek.

At least 91 records · Page 5Linked to original sources

Calcium-dependent effects of cadmium on energy metabolism and function of perfused rat heart.

Postequilibrated isolated rat hearts were perfused for 60 min with a standard supporting electrolyte buffer containing one of the following calcium concentrations: 0.9, 1.8, 3.5, or 5.0 mM, either with or without added cadmium. Doses of cadmium which proved to be minimally (0.03 microM Cd)--and maximally (3.0 microM Cd)--effective at 0.9 mM Ca were studied at all other calcium concentrations. A dose-dependent positive inotropy that persisted throughout the 60-min perfusion period was induced by the graded increases in the perfusate calcium concentration throughout the range from 0.9 to 5.0 mM. Atrioventricular node conductivity was prolonged significantly in hearts perfused with 0.9 mM Ca as compared to hearts perfused with higher calcium concentrations. Increasing the perfusate calcium concentration caused a dose-dependent increase in heart glycerol 3-phosphorylcholine (GPC) content. The other measured phosphatic metabolites of the heart were not altered significantly by varying the perfusate calcium level. In contrast, cadmium (3.0 microM Cd) induced extensive functional and metabolic aberrations which varied in magnitude as an inverse function of the perfusate calcium concentration. Contractile tension, rate of tension development (dT/dt), heart rate, coronary flow rate, and atrioventricular node conductivity were decreased significantly in response to cadmium perfusion. Moreover, these hearts characteristically had significantly elevated low energy phosphate (inosine monophosphate and inorganic phosphate) and decreased high energy phosphate (ATP, PCr) levels relative to their respective calcium controls. Furthermore, various phosphorylated intermediates of glycolysis (glucose 6-phosphate, fructose 6-phosphate, glucose 1-phosphate), as well as glycerol 3-phosphate, and uridine diphosphoglucose accumulated significantly in hearts perfused with cadmium at certain calcium concentrations below 5.0 mM. The calcium-activated increase in heart GPC was inhibited completely by 3 microM cadmium. At the minimally effective dose of cadmium (0.03 microM), demonstrable changes were apparent only at the lowest perfusate calcium concentration examined (0.9 mM). These findings are consistent with the hypothesis that cadmium interferes with calcium-activated and calcium-mediated physiologic and biochemical processes of the mammalian heart. The primary mechanistic basis for the action of cadmium appears to be linked to a competition with calcium for membrane and possibly intracellular binding and activation sites.

Animals↗

Nondestructive metabolic analysis of a cornea with the use of phosphorus nuclear magnetic resonance.

The viability of corneal donor material for penetrating keratoplasty depends on the metabolic status of the tissue; application of nondestructive nuclear magnetic resonance (NMR) techniques to the evaluation of donor tissue metabolism may provide information that would allow improved selection of donor material. The NMR spectrum generated from a single intact cornea permits qualitative and quantitative analysis of the following phosphatic metabolites: the sugar phosphates, inorganic orthophosphate, the alpha- and beta-phosphates of adenosine diphosphate and adenosine triphosphate, and the gamma-phosphate of adenosine triphosphate. Furthermore, the intracorneal pH (6.8) can be monitored from the resonance shift position of inorganic orthophosphate and can serve as an additional indicator of metabolic viability. To our knowledge, this study is the first to demonstrate the feasibility of the use of phosphorus NMR to monitor the metabolic status of a single intact cornea preserved in culture medium.

Adenosine Diphosphate↗

Ex vivo metabolic analysis of eye bank corneas using phosphorus nuclear magnetic resonance.

Application of nondestructive and noninvasive nuclear magnetic resonance (NMR) techniques to the evaluation of corneal donor tissue metabolism may provide information that would allow improved selection of donor material for keratoplasty. A phosphorus 31 NMR spectrum was generated from a single intact human cornea, evaluating phosphatic metabolites qualitatively and quantitatively. The NMR analyses were conducted on four corneas (from patients aged from 73 to 75 years). Intracorneal pH (7.2) was monitored from the resonance shift position of inorganic orthophosphate (Pi). A numerical index (1.15) of tissue energy status was determined by comparing the relative tissue content of high-field, high-energy phosphate signals (adenosine triphosphate, adenosine diphosphate, nicotinamide-adenine dinucleotide, and the uridine diphospho-hexoses) to that of the low-field, low-energy phosphate signals (Pi, sugar phosphates, and phosphodiesters). This is the first demonstration of the feasibility of using nondestructive 31P NMR to monitor the metabolic status of a single intact eye bank cornea as would be required in the evaluation of eye bank tissue before keratoplastic procedures.

Adenosine Diphosphate↗

Metabolic status of fresh v eye-bank-processed corneas. A phosphorus nuclear magnetic resonance study.

The concentrations of corneal phosphatic metabolites in fresh and eye-bank-processed corneas were measured by phosphorus 31 nuclear magnetic resonance of perchloric acid corneal extracts to determine whether metabolic differences exist between these two corneal preparations. Cat corneas were prepared using an eye-bank protocol, including specular microscopic examination and transport to a distant location. Fresh cat corneas were used as controls. The hexose 6-phosphate resonance band, the nucleoside monophosphate band, the phosphodiesters, and adenosine triphosphate of eye-bank-processed corneas were significantly decreased relative to fresh control corneas. Phosphatic metabolites that significantly increased relative to control corneas included inorganic orthophosphate and phosphocreatine. A calculated corneal tissue-energy index was significantly decreased for eye-bank-processed corneas relative to control. This decline demonstrates a compromise in the metabolic energy status of the tissue and is indicative of a diminished ability of the cornea to maintain its complement of high-energy phosphates.

Adenosine Triphosphate↗

P-31 nuclear magnetic resonance analysis of brain: normoxic and anoxic brain slices.

Perchloric acid extracts were prepared from liquid-N2-frozen gerbil and guinea pig brain slices studied under one of three conditions: O2-incubated, N2-incubated or O2-incubated recovery following N2 incubation. Mole percentages of the various phosphatic components contained in the extracts were determined by phosphorus-31 nuclear magnetic resonance spectroscopy. The brain slice extract spectrum revealed a previously unreported group of brain phosphodiesters at -0.73 delta relative to 85% orthophosphoric acid. Although the phosphatic profiles from O2-incubated slices from gerbils and guinea pigs revealed only minor species variations, which differed quantitatively rather than qualitatively, species-specific differences were made readily apparent and amplified by incubating brain slices under oxygen-deficient conditions. Despite these differences which were most prevalent during the recovery phase, the overall metabolic changes described herein in response to N2-incubation were in accord with the results obtained by other analytical techniques. Inorganic orthophosphate (2.63 delta) was increased, while nucleoside (principally, adenosine) triphosphate (alpha-, -10.92 delta, beta-, -21.45 delta, and gamma-, -5.80 delta) and phosphocreatine (-3.12 delta) levels were decreased in response to N2 incubation. In addition, inosine monophosphate (3.78 delta) was increased and the levels of a partially characterized acid-labile phosphate (0.85 delta, guinea pig) were decreased upon N2 incubation. Phosphoglyceride metabolism also appeared to be altered by oxygen deprivation (gerbil). These latter findings provide additional information concerning the metabolic responses of cerebral tissue to oxygen deficient conditions.

Adenine Nucleotides↗

31P nuclear magnetic resonance studies of anoxia in aged rat brain.

In addition to confirming previously reported findings related to changes in high-energy phosphates consequent to anoxia, 31P nuclear magnetic resonance studies of rat brain indicated that maintenance of energy-rich phosphates is less effective in the aged brain than in the mature cerebrum.

Adenosine Triphosphate↗

31P nuclear magnetic resonance spectroscopic evidence for ternary complex formation of fetal dentin phosphoprotein with calcium and inorganic orthophosphate ions.

The single phosphoprotein of fetal calf dentin, having a molecular weight of approximately 94,000 and a phosphorus content of 8% (w/w), was examined by 31P NMR spectroscopy. The single resonance at 3.7 ppm at pH 10 and its chemical shift during acid titration established the phosphomonoester nature of the organic phosphorus moiety. During titration of the phosphoprotein with CaCl2 in the presence of inorganic orthophosphate ions, line broadening for the orthophosphate resonance was both phosphoprotein- and calcium-dependent, indicating ternary complex formation. The data indicate that the phosphoprotein of fetal calf dentin binds both calcium and inorganic orthophosphate ions and therefore has the requisite physical chemical properties necessary for it to facilitate the heterogeneous nucleation of a Ca-PO4 solid phase from solution during tissue mineralization.

Animals↗

Dynamic changes in intact crystalline lens metabolism modulated by alkaline earth metals: I. Effects of magnesium.

Dynamic changes in organophosphate levels during incubation of the intact crystalline lens in Earle's buffer containing 10 and 20 mM-MgCl2 were studied using phosphorus-31 nuclear magnetic resonance spectroscopy. Twenty-eight phosphatic metabolites of intermediary metabolism were quantitated and the utilization of these compounds was determined during a 24-hr time-course. In addition, intralenticular pH was assessed from both the resonance position of alpha-glycerophosphate and inorganic orthophosphate as measured in the intact tissue. Generally, high extracellular magnesium concentrations promote a net reduction of ATP with a concomitant production of inorganic orthophosphate; however, subtle changes occur in the metabolic processes which modulate this primary activity. The most notable difference between incubation in 10 and 20 mM-magnesium is that during 20 mM-magnesium incubations the intralenticular pH decline is proportionate to the net ATP consumption; however, in response to 10 mM-magnesium, the intralenticular pH becomes alkalotic in conjunction with the decrease in intralenticular ATP levels. The demonstration that high extracellular magnesium concentrations significantly alter lens metabolite levels is presumptive evidence that lens metabolic activity may be modulated through cellular mechanisms involving magnesium-sensitive processes.

Adenosine Triphosphate↗

Phosphatic metabolites of the intact cornea by phosphorus-31 nuclear magnetic resonance.

The principal low molecular weight phosphatic metabolites of the intact cornea were identified and quantitated nondestructively by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy. As part of this analytical procedure, the intracorneal pH was approximated from the resonance shift position of inorganic orthophosphate. In addition the metabolic and pH stability of incubated corneas at 37 C in MK medium was evaluated during an 8-hr time course and compared to similar dynamic analyses performed on corneas with denuded endothelium. Perchloric acid extracts prepared from these same corneas were analyzed by P-31 NMR to verify the metabolite peak assignments and to quantitate the concentrations of minor corneal metabolites. The concentrations of phosphatic metabolites of the cornea, including three previously unidentified phosphorus-containing substances, were determined for freshly excised corneas. The initial corneal spectroscopic profile was not altered by removal of the endothelium. At 37 C the MK media-incubated intact whole corneas experienced a time-dependent decline in ATP levels with a concomitant rise in inorganic orthophosphate; however, the tissue levels of the other principal phosphatic metabolites were not altered by prolonged incubation. In contrast, removal of the endothelial layer of the cornea-induced progressive metabolic deterioration of intact corneas characterized, most prominantly, by time-dependent declines in ATP and glycerol 3-phosphorylcholine levels and concomitant increases in ADP and inorganic orthophosphate levels relative to intact whole corneas. This study has established the feasibility of monitoring the metabolic status of intact rabbit corneas nondestructively and noninvasively. As such, P-31 NMR spectroscopy offers a promising method that may enable analysis of the metabolic viability of intact human donor corneas to provide a basis for selecting donor corneas for transplantation.

Adenosine Triphosphate↗

Cardiovascular actions of cadmium at environmental exposure levels.

A low intake of dietary cadmium induces specific dose-dependent functional and biochemical changes in the cardiovascular tissues of rats. Maximum changes occur when the cadmium intake is 10 to 20 micrograms per kilogram of body weight per day. The changes reflect the accumulation of "critical" concentrations of cadmium in the cardiovascular tissues. The biologic activity of cadmium is demonstrated for intakes that approach those of the average American adult exposed to the usual environmental concentrations of the element but not to industrial concentrations. The sensitivity of the cardiovascular system to low doses of cadmium could not be anticipated by extrapolation from data on exposure to high concentrations of cadmium. The data support the hypothesis that ingested or inhaled environmental cadmium may contribute to essential hypertension in humans.

Adenosine Triphosphatases↗

Interspecies variations in mammalian lens metabolites as detected by phosphorus-31 nuclear magnetic resonance.

Multiple interspecies differences were detected between humans and seven other mammals in 15 of the 24 metabolites measured in the intact crystalline lens and lens perchloric acid extracts. Generally, the number of statistically significant metabolite differences among the various species, relative to the human, increase in the following order: cat or approximately dog greater than pig greater than rat greater than sheep greater than rabbit greater than cow.

Adenine Nucleotides↗

Dynamic changes in the organophosphate profile of the experimental galactose-induced cataract.

Dynamic changes in lens organophosphate metabolites during 24 hr incubation in 30 mM galactose media were measured with phosphorus-31 nuclear magnetic resonance spectroscopy. The following phosphates were quantitated from the intact crystalline lens: adenosine triphosphate (ATP), adenosine diphosphate (ADP), inorganic orthophosphate, alpha-glycerophosphate, phosphorylated hexoses and trioses, nicotinamide adenine dinucleotide, uridine diphosphoglucose and uridine diphosphogalactose, glycerol-3-phosphorylethanolamine and 3-phosphorylcholine, and an unidentified phosphorus-containing molecule. The temporal sequences of metabolic events that define the dynamic rates of accumulation or depletion of lens organophosphates reveal that the first event in the decline of the tissue upon galactose incubation is a net consumption of ATP, which occurs as a sigmoidal function with time and which is typified by a characteristic half-life of 18 hr. Alpha-glycerophosphate accumulated at an increasing rate with time, whereas ADP, inorganic orthophosphate, and the other organophosphates were essentially unchanged. Cataract formation in the subcapsular and superficial cortical regions was visible after 16 hr incubation in the experimental buffer. These findings support the hypothesis that alterations in the organophosphate levels of the lens are contributing factors to the initial formation of the experimental galactose cataract.

Adenosine Diphosphate↗

Dynamic changes in the organophosphate profile upon treatment of the crystalline lens with dexamethasone.

Dynamic changes in organophosphate metabolites during incubations of the intact crystalline lens in a medium containing 2 X 10(-3) M dexamethasone were studied using phosphorus-31 nuclear magnetic resonance intact-tissue spectroscopy. ATP, ADP, inorganic orthophosphate, alpha-glycerophosphate, nicotinamide adenine dinucleotides, uridine diphosphorylglucose and diphosphorylgalactose, glycerol 3-phosphorylethanolamine and -phosphorylcholine, and an unidentified phosphorus-containing molecule at 6 ppm were quantitated. Time-dependent changes in lens metabolism involving these compounds were examined during a 24-hr incubation period with dexamethasone. The first event in the decline of the tissue after steroid incubation was the consumption of ATP, which was linear with time until the ATP was reduced to 10% of its initial value. The sugar phosphates, inorganic orthophosphate, and the nucleoside diphosphorylsugars increased linearly with time, whereas the dinucleotides decreased. The ADP concentration was unaffected by the steroid treatment, as was that of the other organophosphates in the intact tissue profile. The steroid-induced alterations in lens phosphate metabolite levels follow a distinctive pattern that differs substantially from that observed in response to experimental hypoglycistic or hyperglycistic conditions. These findings suggest that pharmacologic steroid doses may directly alter lens metabolism through a complex mechanism involving, at least in part, a steroid-mediated antagonism of lens glucose uptake and/or utilization.

Adenosine Diphosphate↗

Analysis of intact rat lens metabolites by P-31 NMR spectroscopy.

Using phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy the rat crystalline lens was evaluated as a potential animal model for the study of lens metabolic processes relevant to the human. The P-31 NMR spectra of intact rat lenses and rat lens PCA extracts provided comparable qualitative and quantitative results concerning the tissue levels of the phosphorus-containing metabolites of intermediate metabolism. The study also establishes the feasibility of examining intact rat lens metabolism by P-31 NMR. Comparisons with reported human and rabbit lens metabolite levels revealed significant differences; consequently, metabolic information derived from rat lens studies should be extrapolated to the human with caution.

Animals↗