Ethanol and sucrose self-administration components: effects of drinking history.

Results of previous studies have shown that when rats consume higher concentrations of ethanol during initiation both the amount consumed and the pattern of consumption change with the return to a lower concentration. In this study, an across-sessions breakpoint procedure in the sipper-tube model was used to examine the effect that experience with drinking higher concentrations (a concentration manipulation) of both ethanol and sucrose had on appetitive and consummatory behaviors. A follow-up study was then conducted in the ethanol-consuming group with across-session breakpoint and intake examined before, during, and after a 3% sucrose/10% ethanol solution was presented in the sipper tube. As ethanol concentration increased, intake was not changed. Exposure to higher ethanol concentrations had no effect on the amount of 10% ethanol consumed when retested. The exposure tended to increase appetitive behavior (breakpoint), but this effect was not unique to ethanol, as rats self-administering 3% sucrose showed a similar increase. When the combined ethanol-sucrose solution was available, a significant increase in both intake and appetitive responding occurred; however, there was no change from prior intake or breakpoint when 10% ethanol was retested. That the addition of sucrose to the ethanol solution significantly increased appetitive and consummatory behaviors supports the suggestion that the composition of the alcoholic beverage can have a strong influence over the control of self-administration. Because most consumption of ethanol by human beings is in solutions that contain mixers that alter the taste of the solution, this taste factor needs to be considered in the regulation of ethanol drinking.     

Direct measurement of the lambda of the lumped constant of the deoxyglucose method in rat brain: determination of lambda and lumped constant from tissue glucose concentration or equilibrium brain/plasma distribution ratio for methylglucose

Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3-O-[14C]methylglucose at various concentrations of glucose in brain and plasma ranging from hypoglycemic to hyperglycemic levels have been determined by direct chemical analyses in the brains of conscious rats. The hexose concentrations were measured chemically in freeze-blown brain extracted with ethanol to avoid the degradation of acid-labile products of [14C]DG back to free [14C]DG that has been found to occur with the more commonly used perchloric acid extraction of brain. Corrections were also made for nonphosphorylatable, labeled products of [14C]DG found in the nonacidic fractions of the brain extracts, which were previously included with the assayed [14C]DG, and for the contribution of the hexose contents in the blood in the brain, which was found to be particularly critical for the determination of the glucose distribution space, especially in hypoglycemic states. From the measured contents of the hexoses in brain and plasma, the relationships of the tissue concentrations and distribution spaces of each of the hexoses and of the lambda (i.e., ratio of tissue distribution space of DG to that of glucose) of the DG method to the tissue glucose concentration were derived. The lambda was then quantitatively related to the measured equilibrium ratio for [14C]methylglucose over the full range of brain and plasma glucose levels. By combining these new data with the values for the lumped constant, the factor that converts the rate of DG phosphorylation to glucose phosphorylation, previously determined in rats over the same range of plasma glucose levels, the phosphorylation coefficient was calculated and the lumped constant graphed as a function of the measured distribution space in brain for [14C]methylglucose.     

Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant

The steady-state distribution volumes of glucose, 3-O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 mM. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.     

Effect of dipyridamole with or without aspirin on urine protein excretion in patients with membranous glomerulonephritis

Summary The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibiton of thromboxane B₂ (TxB₂) synthesis in 8 patients with confirmed membranous glomerulonephritis. There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300 mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB₂ were measured. Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h protein excretion; the latter amounted to 54% with dipyridamole alone and 56 % with dipyridamole plus aspirin (NS). Dipyridamole plus aspirin caused an 82 % reduction in serum TxB₂.     

An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8.

An immunochemical analysis was conducted to compare the C1 isomer of human myelin basic protein (MBP) with the newly described and less cationic, citrullinated isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple epitopes or restricted regions of MBP were used in radioimmunoassays to examine MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP-C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same. With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA), differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most notably near the amino terminus.     

Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo

We have investigated the ability of recombinant TNF (mouse and human) to produce acute inflammatory lesions in an established experimental model of inflammation. Upon intradermal injection in rabbit skin, TNF, in amounts as low as 3 x 10(-14) mol/site, was found to be very potent at inducing local neutrophil accumulation and neutrophil-dependent oedema formation, thereby fulfilling two important criteria to be considered as an inflammatory mediator. Our findings further indicate that the pro-inflammatory properties of TNF are probably more related to its immediate stimulatory effects on neutrophils rather than to its slow (protein biosynthesis-dependent effects on endothelial cells. Our data thus show that very low amounts of mouse and human recombinant TNF can initiate an acute inflammatory reaction in vivo in rabbit skin and that TNF is able to evoke two of the four cardinal signs of inflammation.