Biomedical subjects

D Holtzman

Publications and source records attributed to D Holtzman.

At least 55 records · Page 3Linked to original sources

PubMed1994

Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after hypothermic circulatory arrest.

Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15 degrees C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. Equivalent doses were placed in the cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg kg-1h-1 and 5 mg kg-1h-1). Changes in high-energy phosphate concentrations and pH were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min after reperfusion. Cerebral blood flow determined by radioactive microspheres as well as cerebral oxygen and glucose consumption were studied in 17 other animals. Cerebral blood flow and oxygen consumption were depressed relative to control by both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded by NBQX over the 45 min of rewarming reperfusion and the first hour of normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion was significantly reduced by NBQX (46 +/- 26% baseline, mean +/- SD) versus control (81 +/- 19%) and MK-801 (75 +/- 8%) (p = 0.030). Cerebral oxygen consumption recovered to 105 +/- 30% baseline in group MK-801 and 94 +/- 31% in control but only to 61 +/- 22% in group NBQX (p = 0.070). Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.

Animals↗

PubMed1994

Changes in HIV-related information sources, instruction, knowledge, and behaviors among US high school students, 1989 and 1990.

OBJECTIVES: Few data have been available among adolescents to determine behavioral changes that may prevent human immunodeficiency virus (HIV) infection. This analysis examines changes in the prevalence of self-reported HIV-related information sources, instruction, knowledge, and behaviors among high school students in the United States. METHODS: Two independent, multistage national probability samples of students in grades 9 through 12 were surveyed in 1989 (n = 8098) and 1990 (n = 11,631) with self-administered, anonymous questionnaires that included similar items. RESULTS: Compared with students surveyed in 1989, a significantly greater proportion of students surveyed in 1990 had received HIV instruction in school. Significant decreases were found in the proportion of White and female students who reported having had sexual intercourse, in the proportion of White students reporting two or more lifetime sex partners, and in the proportion of 15- and 16-year-olds, White students, and female students who reported having had four or more lifetime sex partners. For both years, students who had a greater level of HIV knowledge were less likely to have had multiple lifetime sex partners or to have injected illicit drugs. CONCLUSIONS: The findings suggest that school-based HIV education and knowledge may be contributing factors in reducing certain risk behaviors that can lead to HIV transmission among secondary school youth.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Substance use and HIV-related sexual behaviors among US high school students: are they related?

OBJECTIVES: This study was undertaken to examine whether use of alcohol, cigarettes, marijuana, cocaine, and other illicit drugs is related to the likelihood of sexual behaviors that increase risk for human immunodeficiency virus (HIV) infection among youth. METHODS: The 1990 national Youth Risk Behavior Survey was used to collect self-reported information about a broad range of health risk behaviors from a representative sample of 11,631 high school students in the United States. RESULTS: Students who reported no substance use were least likely to report having had sexual intercourse, having had four or more sex partners, and not having used a condom at last sexual intercourse. Adjusted for age, sex, and race/ethnicity, odds ratios for each of these sexual risk behaviors were greatest among students who had used marijuana, cocaine, or other illicit drugs. Students who had used only alcohol or cigarettes had smaller but still significant increases in the likelihood of having had sexual intercourse and of having had four or more sex partners. CONCLUSIONS: HIV prevention programs for youth should recognize that substance use may be an important indicator of risk for HIV infection and acquired immunodeficiency syndrome through its association with unsafe sexual behaviors.

Adolescent↗

PubMed1994

Effects of cerebroplegic solutions during hypothermic circulatory arrest and short-term recovery.

UNLABELLED: Previous studies have suggested that a simple crystalloid "cerebroplegic" solution may prolong the safe duration of hypothermic circulatory arrest. We tested the hypothesis that pharmacologic modification of the cerebroplegic solution would further enhance cerebral protection. Forty-six 4-week-old miniature piglets underwent core cooling to 15 degrees C nasopharyngeal temperature and 2 hours of hypothermic circulatory arrest. Twelve animals had a 50 ml/kg dose of saline infused into the carotid artery system at the onset of hypothermic circulatory arrest and repeat doses of 10 ml/kg every 30 minutes during arrest. Eleven animals received the same initial and repeat doses of University of Wisconsin organ preservation solution and 10 received University of Wisconsin solution with 7.5 mg/L of MK-801, an excitatory neurotransmitter antagonist. In 13 control animals blood was partially drained from the piglet before 2 hours of circulatory arrest at 15 degrees C and no cerebroplegic solution was infused. All solutions were delivered at 4 degrees C. Brain temperature (n = 24) at the onset of hypothermic circulatory arrest was 15.0 degrees +/- 0.1 degrees C (mean +/- standard error). Brain temperature after cerebroplegic infusion dropped to 13.0 degrees +/- 0.3 degrees C and stayed lower than brain temperature in the control group throughout the hypothermic circulatory arrest period. Recovery of cerebral adenosine triphosphate and intracellular pH determined by phosphorus 31 magnetic resonance spectroscopy (n = 22) was significantly improved by saline infusion and was further improved with University of Wisconsin solution and University of Wisconsin solution plus MK-801 (p < 0.001). Recovery of cerebral blood flow measured by microspheres (n = 24) also was augmented by University of Wisconsin solution (p < 0.001) but not in the presence of MK-801. The vascular resistance response to acetylcholine and nitroglycerin suggested that MK-801 has a direct vasoconstrictive effect. Recovery of cerebral oxygen consumption (n = 24) was increased by University of Wisconsin solution and University of Wisconsin solution with MK-801 (p = 0.002). Brain water content (n = 46) was significantly lower in all cerebroplegia-treated groups than in controls (p < 0.001). CONCLUSION: Cerebroplegia improves short-term recovery after 2 hours of circulatory arrest in hypothermic piglets. Pharmacologic modification with University of Wisconsin solution further improves the recovery of cerebral blood flow and metabolism. MK-801 does not augment the protective effects of University of Wisconsin solution and reduces the recovery of cerebral blood flow by a direct vascular action. Modified cerebroplegia may provide a novel approach to improved cerebral protection when prolonged hypothermic circulatory arrest is necessary.

Adenosine↗

PubMed1993

Profound, reversible energy loss in the hypoxic immature rat brain.

The goal of this study was to compare the effects of oxygen deprivation on cellular energy state and pH in the developing and adult rat brain. Relative quantities of phosphocreatine (PC), inorganic phosphorus (P(i)), and nucleoside triphosphates (NTP), and intracellular pH, were determined using in vivo 31P NMR spectroscopy at different postnatal ages (postnatal day (P) 2-6, P9-13, P16-20, P23-27) in the hypoxic rat brain (7 min, 4% O2). While a significant increase in P(i) was seen at all ages during hypoxia, a severe but reversible reduction in concentrations of PC (80-100% decrease) and NTP (40-50% decrease) was observed only at P9-13. This dramatic response was not seen in older (> P16) or younger (< P6) animals. These latter groups responded with moderate decreases in brain PC (50-60% decrease) and NTP (20-40% decrease). In addition, the youngest animals showed much less intracellular brain acidosis than the other age groups. The transient period of development during which the brain exhibits heightened susceptibility to hypoxic energy failure coincides with known changes in brain energy production pathways and susceptibility to hypoxia-induced excitability.

Adenosine Triphosphate↗

PubMed1993

Sports participation, age at smoking initiation, and the risk of smoking among US high school students.

OBJECTIVE: To examine smoking patterns, smoking initiation, and the relationship of sports participation and age at smoking initiation to regular and heavy smoking among adolescents. DESIGN: Survey. PARTICIPANTS: A nationally representative sample of US high school students. OUTCOME MEASURES: Prevalences of smoking patterns, prevalence and incidence of smoking initiation, and prevalences and odds of regular and heavy smoking in relation to sports participation and age at smoking initiation. RESULTS: Seventy-two percent of students reported experimenting with, formerly, or ever smoking cigarettes, and 32% reported smoking in the past 30 days. Students who had participated in interscholastic sports were less likely to be regular and heavy smokers than were others who had not participated. Smoking initiation rates increased rapidly after age 10 years and peaked at age 13 to 14 years. Students who began smoking at age 12 years or younger were more likely to be regular and heavy smokers than were students who began smoking at older ages. CONCLUSIONS: These data suggest that smoking initiation at a young age can increase the risk of nicotine addiction during adolescence and that sports participation may influence smoking behavior. Interventions to prevent smoking should be available before age 12 years to help combat the smoking epidemic among youth.

Adolescent↗

PubMed1993

Creatine kinase-catalyzed reaction rate in the cyanide-poisoned mouse brain.

Brain creatine kinase (CK)-catalyzed phosphorus flux from phosphocreatine (PC) to ATP was measured in vivo in young adult mice made reversibly hypoxic by injection of cyanide. Phosphorus spectra and saturation transfer measurements of CK-catalyzed flux were acquired using a high-field (8.45 T) nuclear magnetic resonance (NMR) spectrometer. After low cyanide doses (1-3 mg/kg of body weight), there were no measurable changes in brain pH or in concentrations of PC, the nucleoside triphosphates (including ATP), and Pi. The CK-catalyzed phosphorus flux increased about 75% after the low cyanide dose. Higher doses (4-6 mg/kg) produced a transient 30-40% decrease in PC concentration, doubling of Pi, and a 0.2 unit decrease in pH. The CK-catalyzed phosphorus flux decreased 50-80% after the higher cyanide doses. This decrease in phosphorus flux was present long after reactant concentrations returned to precyanide values. It is proposed that the increase in brain CK-catalyzed phosphorus flux with the lower cyanide doses is due to an increase in ADP concentration. The large, prolonged decrease in CK-catalyzed reaction rate in the moderately poisoned brain may be due to loss of activity of the mitochondrial CK isoform.

Adenosine Triphosphate↗

PubMed1993

Functional maturation of creatine kinase in rat brain.

The physiological role of the phosphocreatine (PCr)/creatine kinase (CK) system has been studied in rat brain by comparing maturational changes in in vivo CK-catalyzed reaction rate and activities of CK isoenzymes. The CK-catalyzed reaction rates, measured by 31P-nuclear magnetic resonance spectroscopy, increased 4-fold between 12 and 17 days of age. The mitochondrial CK (Mi-CK) isoenzyme, as a percentage of total CK, increased to the same extent over this relatively narrow age period. Cytosolic CK (B-CK) was active earlier and, with the total CK activity, increased steadily over a longer time course. An immunohistochemical study of cerebellum showed Mi-CK predominantly in gray matter, while the cytosolic CK was present in rather large concentrations in both gray and white matter. In the molecular layer, B-CK was most prominent in the Bergmann glial cells, while Mi-CK was more prominent in Purkinje neurons. During development a redistribution of Mi-CK from the Purkinje cell bodies to their processes was observed. These results point to regional differences in CK content and in isoenzyme-specific localizations. The increase in CK activity is temporally coincident with the maturational appearance of closely coupled decreases in brain PCr and ATP during hypoxia. These maturational changes suggest that the activity of the PCr/CK system, particularly the Mi-CK isoenzyme, is central in regulation of brain ATP.

Animals↗

PubMed1993

Recovery of cerebral blood flow and energy state in piglets after hypothermic circulatory arrest versus recovery after low-flow bypass.

A miniature piglet model that replicates clinical hypothermic (14 degrees C nasopharyngeal) circulatory arrest and low-flow (50 ml/kg per minute) bypass was used to study carotid blood flow with electromagnetic flow probe, cerebral blood flow by microsphere injection, cerebral metabolic rate by arteriovenous oxygen and glucose extractions, lactate production by cerebral arteriovenous difference, and cerebral edema. Data from five animals that underwent circulatory arrest and five animals that underwent low-flow bypass (aged 28.8 +/- 0.4 [mean +/- standard error of the mean] days) were analyzed. The duration of circulatory arrest and low-flow bypass was 1 hour. In a parallel study with the same animal model, phosphorus 31 magnetic resonance spectroscopy was used to assess cerebral phosphocreatine, nucleoside triphosphate (adenosine triphosphate), and intracellular pH. Five animals (aged 31.8 +/- 1.1 days) underwent circulatory arrest, and five underwent low-flow bypass. A brief phase of hyperemic carotid blood flow was seen immediately after the onset of reperfusion in the circulatory arrest group but not in the low-flow group. In the circulatory arrest and low-flow bypass groups, cerebral blood flow (percentage of baseline 71.2% +/- 8.3% and 69.1% +/- 5.8%, respectively), cerebral oxygen consumption (45.6% +/- 10.0%, 44.5% +/- 7.6%), and cerebral glucose consumption (31.5% +/- 30.7%, 83.5% +/- 24.2%) remained depressed after 45 minutes of reperfusion and rewarming to normothermia. However, after 3 more hours of pulsatile normothermic reperfusion, cerebral oxygen consumption and cerebral glucose consumption had returned to baseline. Phosphocreatine, adenosine triphosphate, and pH were maintained at or above baseline levels throughout low-flow bypass and throughout 3 hours of normothermic reperfusion. In contrast, both phosphocreatine and adenosine triphosphate became undetectable 32 +/- 3.7 minutes after onset of circulatory arrest. During and early after circulatory arrest, pH decreased to a minimum of 6.506 +/- 0.129 at 40 minutes after reperfusion. After 3 hours of normothermic reperfusion, phosphocreatine and adenosine triphosphate recovered to 98.6% +/- 9.0% and 90.1% +/- 13.5% of baseline, respectively, and pH was 7.087 +/- 0.051, similar to baseline (7.1755 +/- 0.041). In the low-flow bypass group, the disparity between the depressed level of cerebral oxygen consumption and normal high-energy phosphate levels may reflect incomplete cerebral rewarming or decreased energy consumption. In the circulatory arrest group, the parallel recovery of oxygen consumption and high-energy phosphates eventually achieving baseline levels suggests that the degree of hypothermia used provides adequate protection for acute cerebral recovery after 1 hour of circulatory arrest.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1992

Astrocyte volume regulation and ATP and phosphocreatine concentrations after exposure to salicylate, ammonium, and fatty acids.

Cellular volume regulation following swelling in hypo-osmotic phosphate-buffered saline (PBS) and ATP and phosphocreatine concentrations of cells incubated in iso-osmotic or hypo-osmotic PBS were measured in primary cultured rat cerebral astrocytes exposed for 30 min to NH4Cl, salicylate, hexanoate, octanoate, and/or dodecanoate. These compounds have been implicated in the pathogenesis of cerebral edema in Reye's Syndrome. NH4Cl (0.10 - 10 mM) had no effect on astrocyte volume regulation or ATP concentration. Salicylate significantly reduced ATP concentrations at 3.0 mM and 10 mM but had no effect on volume regulation. Hexanoate (10 mM and 30 mM) decreased astrocyte ATP content by over 80% while octanoate (10 mM) reduced ATP content by more than 50%. Concentrations of these fatty acids at or below 3.0 mM had no effect on ATP content. Volume regulation was inhibited by 3.0 mM hexanoate and 3.0 mM octanoate but not lower concentrations. Dodecanoate (0.1-3.0 mM) decreased cellular ATP content by 33-51% in iso-osmotic PBS solutions. Phosphocreatine content was reduced by exposure to salicylate or octanoate at concentrations which had no effect on ATP content. These results indicate that astrocyte energy metabolism and volume regulation may be compromised by agents associated with cerebral edema in Reye's Syndrome. Analysis of the dose-dependence of these effects suggests that inhibition of astrocyte energy metabolism is not sufficient to affect volume regulation.

Adenosine Triphosphate↗

PubMed1992

Synergism between occupational arsenic exposure and smoking in the induction of lung cancer.

We assembled data from numerous studies to examine whether active smoking and occupational exposure to arsenic act synergistically (more than additively) to increase the risk of lung cancer. Although several smaller studies lacked the power to reject simple additive relations, the joint effect from both exposures consistently exceeded the sum of the separate effects by about 70 to 130%. The only study not showing a greater than additive effect appeared to have inadequate data to address this question. We calculated the excess fractions for the synergism; these showed that a minimum of between 30% and 54% of lung cancer cases among those with both exposures could not be attributed to either one or the other exposure alone. Previous authors addressing the synergism between arsenic exposure and smoking have evaluated deviations from a multiplicative model, which is inappropriate for this purpose. Reports of no interaction or "negative" interaction have therefore been misleading. Taken as a whole, the evidence is compelling that arsenic and smoking act in a synergistic manner to produce lung cancer. Substantial reductions in the lung cancer burden of smokers occupationally exposed to arsenic could be achieved by reductions in either exposure. The mechanism for the synergism is unclear.

Arsenic↗

PubMed1992

HIV education and health education in the United States: a national survey of local school district policies and practices.

To determine the extent to which HIV education and health education policies and practices are required by school districts in the United States, a national probability sample of public school districts was surveyed by mail in 1990. Of 2,150 districts selected, 78.1% responded. HIV education was required by 66.9% of districts. Of these, the percentage requiring HIV education increased by grade level from 29.7% in kindergarten to 82.3% in 7th grade, then declined to 37.3% by 12th grade. Districts that required HIV education most often addressed HIV-related prevention skills in the upper grade levels. Similar to requirements for HIV education, health education requirements also declined from 7th to 12th grade, reaching even lower levels than HIV education by the last two years of high school. These declines are of particular concern given that students are most likely to engage in risk behaviors when HIV and health education is least likely to be required. Other practices and policies that support HIV and health education also were lacking in many districts.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Maturational increase in mouse brain creatine kinase reaction rates shown by phosphorus magnetic resonance.

In-vivo phosphorus fluxes in the reaction catalyzed by creatine kinase (CK) were measured in brains of mice from 3 to 40 days of age using high-field (8.45 T) phosphorus magnetic resonance and the saturation transfer technique. This technique gives the ratio of chemical flux to reactant concentration directly and allows the calculation of pseudo-rate constants for the forward direction from PC to ATP (kf) and for the reverse direction (kr). The spin-lattice relaxation times (T1) for phosphocreatine (PC) and for the nucleoside triphosphate (NTP) nuclei, estimated by the progressive saturation technique, did not change during this age period. The PC concentration doubled relative to the NTP concentration over the first month of life. The kf and the flux of phosphorus nuclei in the forward direction increased 2- to 3-fold in the very narrow time period from 12 to 15 days of age. Brain phosphorus flux from PC to ATP thus increased 4- to 6-fold in the first month of life. An increase at least that large occurred in the reverse direction, but the kr could not be measured consistently in the younger animals using the saturation transfer technique. Phosphorus fluxes were equal in the forward and reverse directions in the mature brain. The capacity to increase rates of glycolysis and tissue respiration in response to increased energy demand appears in the same narrow age period as the increase in CK-catalyzed reaction rates in the developing rodent brain. We propose that these coincident changes in brain energy metabolism reflect the maturation of mechanisms for coupling cell energy production to rapid changes in energy requirements.

Adenosine Triphosphate↗

PubMed1991

Epileptogenic effect of hypoxia in the immature rodent brain.

The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia.

Age Factors↗

PubMed1991

HIV-related knowledge, beliefs, and behaviors among high school students in the United States: results from a national survey.

The Secondary School Student Health Risk Survey measured the prevalence of sexual intercourse and illegal drug injection among a national probability sample of U.S. high school students and assessed their HIV-related knowledge and beliefs. Ninety-nine (81%) of the 122 selected schools and 8,098 (83%) of the eligible students participated. Nearly all high school students knew the major modes of HIV transmission. Three percent reported injecting illegal drugs, and 1% reported sharing needles used to inject drugs. In addition, 59% of students reported having sexual intercourse and, of students who reported having sexual intercourse, 40% reported having four or more sexual partners. HIV-related knowledge, beliefs, and behaviors among high school students suggest the need for school-based HIV education programs that help young people acquire the knowledge and skills to adopt and maintain behaviors that reduce risk of HIV infection and other related health problems.

Adolescent↗

PubMed1991

HIV instruction, HIV knowledge, and drug injection among high school students in the United States.

BACKGROUND: The prevalence of HIV-related behaviors and determinants of these behaviors among adolescents in the United States have not been well studied. METHODS: To determine the prevalence of HIV-related drug behaviors and to assess the effects of HIV-related school-based instruction and HIV knowledge on these behaviors, data were analyzed from a 39-item, self-administered questionnaire completed by a probability sample of all students in grades 9 through 12 in the United States. RESULTS: Usable responses were obtained from 8098 students. Of these, 2.7% (95% confidence interval [CI] = 2.3-3.2) and 1.7% (95% CI = 1.3-2.1) reported injecting illicit drugs ever and during the past year, respectively. Corresponding prevalences of needle sharing were 0.8% (95% CI = 0.5-1.1) and 0.5% (95% CI = 0.3-0.7). Regression analysis revealed that students with higher knowledge scores were less likely and males more likely to have ever injected drugs. HIV knowledge was similarly associated with other outcome measures of drug-injection behavior. Although HIV instruction did not directly influence drug-injection behavior independently of demographic characteristics, it was positively associated with HIV knowledge. CONCLUSIONS: While these results do not establish a causal relationship, they suggest that HIV knowledge and school-based instruction may play a role in maintaining low levels of drug-injection behavior among high school students.

Adolescent↗

PubMed1990

Control of astrocyte volume by intracellular and extracellular Ca2+.

Astrocytes from primary culture were exposed to conditions that affect intracellular and extracellular Ca2+ concentrations. Astrocyte cell volume was increased approximately 16% after a 30 min exposure to isoosmotic phosphate-buffered saline (PBS) containing the Ca2+ buffer EDTA. Cell volume returned to control values within 30 min of resuspension in normal PBS. Cellular calcium content was not affected by these treatments; however, the recovery of normal cell volume following EDTA exposure was inhibited by 0.1-1.0 mM quinine HCl in a dose-dependent fashion suggesting that a potassium channel controlled by the intracellular Ca2+ concentration is important in this volume response. Intracellular accumulation of an exogenous Ca2+ buffer, BAPTA, also produced cell swelling that persisted following resuspension in normal PBS. Lowering the extracellular Ca2+ concentration with EDTA enhanced the swelling of BAPTA-loaded cells. These data suggest that conditions leading to a decrease in free intracellular Ca2+ concentration may influence astrocyte volume by a mechanism similar to that described in other cell types.

Animals↗

PubMed1989

Brain creatine phosphate and creatine kinase in mice fed an analogue of creatine.

Brain phosphocreatine (PCr) concentration and creatine kinase (CK) activity have been studied by 31P nuclear magnetic resonance (NMR) spectroscopy in mice fed an analogue of creatine, beta-guanidinopropionic acid (GPA). The phosphorylated analogue (GPAP), which almost completely replaces PCr in skeletal muscle, is a poor substrate for CK. Mice, which received GPA in food (2%) and water (0.5%) for up to 9 months beginning at 35 days of age, were normal in appearance and activity. Maximal brain GPAP concentration, reached after two weeks of feedings, was approximately equal to the concentration of PCr. The concentration of PCr decreased at least 20% relative to that of the nucleoside triphosphates. When GPA feedings were stopped, GPAP disappeared in about 20 days from skeletal muscle, but only after 40-50 days from brain. Steady-state NMR saturation transfer studies showed a markedly reduced chemical exchange rate from PCr to ATP in brains of GPA-fed mice. These results suggest a compartmentation of brain PCr. The GPA-accessible PCr compartment has a slow rate of PCr turnover compared to skeletal muscle. The slow reaction rate of the GPA-inaccessible PCr as a CK substrate is consistent with the hypothesis that this residual PCr is the same compartment which is stable in hypoxic or seizing animals.

Adenosine Triphosphate↗