phosphorus-radioisotopes and Alcoholism

Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain.. Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods.. The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08).. These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.

Topics: Adult; Alcoholism; Analysis of Variance; Brain; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phospholipids; Phosphorus Radioisotopes

In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics.. Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously.. Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups.. Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.

Topics: Adult; Alcoholism; Brain; Brain Chemistry; Ethanol; Female; Humans; Magnetic Resonance Spectroscopy; Male; Membrane Lipids; Middle Aged; Phospholipids; Phosphorus Radioisotopes

The adenylyl cyclase (AC) signal transduction pathway is a target of acute and chronic ethanol actions. This study examined whether AC activity in lymphocyte membranes of male alcoholic patients correlated with blood concentrations of ethanol.. Patients (n = 13; mean age: 40 +/- 8 years) were studied on the day of admission (day 0) and 2 days later under detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 +/- 9 years) were included. Lymphocyte membranes were prepared by differential centrifugation whereby blood ethanol was washed out. As a measure of AC activity the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate was determined without (basal activity) and with stimulation of the second messenger system by the guanosine triphosphate (GTP) analogue GTP gamma S (20 mumol/L) via the G-protein or by forskolin (100 mumol/L) acting directly on the AC enzyme.. On day 0, when ethanol blood concentrations were 38-100 mmol/L, we found a significant negative correlation between ethanol blood levels and stimulated AC activities. On day 2, the negative correlation with blood ethanol levels of day 0 had disappeared.. The consumption of ethanol affects the AC system in lymphocytes of alcohol-dependent patients by a persistent effect on the cAMP forming enzyme.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Adult; Alcoholism; Case-Control Studies; Colforsin; Cyclic AMP; Dose-Response Relationship, Drug; Ethanol; Guanosine Triphosphate; Humans; Longitudinal Studies; Lymphocytes; Male; Middle Aged; Phosphorus Radioisotopes; Signal Transduction

The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and nmr observables are discussed. The stability of the ex-vivo preparation based on the nmr observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.

Topics: Alcoholism; Animals; Disease Models, Animal; Dogs; Magnetic Resonance Spectroscopy; Oleic Acid; Oleic Acids; Pancreas; Pancreatitis; Phosphocreatine; Phosphorus Radioisotopes

Adult male rats were given nutritionally balanced high fat (34% corn oil) diets containing either ethanol or isocalorically substituted sucrose for 4-5 weeks. Phosphatidylinositol-phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine contents of whole hepatocytes were not altered in ethanol-treated rats. However, vasopressin and alpha1-adrenergic stimulation of [32P]-incorporation into phosphatidylinositol of isolated hepatocytes from ethanol-treated rats was increased substantially compared to that of controls. Yet, chronic ethanol treatment had no effect on hepatic alpha1 receptor density or affinity as measured by [3H]prazosin specific binding. These results suggest that the supersensitive phosphatidylinositol response to this alpha1 agonist observed in hepatocytes from ethanol-treated rats occurred distal to cell surface receptors and may be similar for vasopressin.

Topics: Alcoholism; Animals; Dietary Fats; Dose-Response Relationship, Drug; Epinephrine; Humans; Lipids; Liver; Male; Phosphatidylinositols; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Cell Surface; Receptors, Vasopressin

Cerebrospinal fluid (CSF) contains two groups of proteins that bind tightly to DNA and to polyriboguanylic acid, respectively. In certain diseases the amounts of a given nucleic acid bound by a constant volume of CSF may increase, while in others the amount of such proteins may be reduced. Binding of polyriboguanylic acid increased in CSF samples from patients with brain tumors, stroke, multiple sclerosis, and communicating hydrocephalus, but it significantly decreased in CSF samples from patients with obstructive hydrocephalus. These increases may or may not be proportional to the rise in total CSF proteins characteristic for these diseases. Elevated binding of DNA was observed in samples from patients with hydrocephalus, epilepsy, and cortical atrophy. The technique described may be applicable to the diagnosis of a variety of diseases of the central nervous system.

Topics: Alcoholism; Astrocytoma; Brain Diseases; Brain Injuries; Brain Neoplasms; Carcinoma; Cerebrospinal Fluid Proteins; Cerebrovascular Disorders; Child, Preschool; DNA; Epilepsy; Female; Guanine Nucleotides; Headache; Humans; Hydrocephalus; Meningioma; Middle Aged; Multiple Sclerosis; Neurilemmoma; Phosphorus Radioisotopes; Polynucleotides; Protein Binding; Schizophrenia; Tritium