Effect of portocaval anastomosis on the incorporation of (U-14C)-D-glucose into protein, cholesterol, and lipid of rat brain

The incorporation of [U—¹⁴C]-D-glucose into lipid and protein of the brains of rats subjected to portocaval anastomosis has been studied from 2 to 20 weeks after the operation. It has been found that there is a reduction by about 30% of the labelling of protein, total lipid and of cholesterol in all experimental animals compared with controls. These findings are discussed in relation to the early astroglial disturbances after liver bypass and the later degenerative changes in terminal neurites that constantly occur in brain in this experimental preparation.     

Pathology of liver necrosis and regeneration after administration of dimethylnitrosamine in massive doses

Two groups of dogs were given dimethylnitrosamine (DMNA), a hepatotoxic drug, in a single lethal dose. Control dogs were allowed to die. Experimental dogs received life-saving auxiliary liver transplants which were removed after recovery of the host liver or when rejection occurred. The histopathologic findings in the host livers of the two groups are presented. Remarkable variations were noted even among livers from the same group. Centrilobular and midzonal congestion and necrosis were the main findings but appeared less severe than one would expect in view of the lethality of DMNA in control dogs. In contrast to the changes noted with long-term administration of the drug to dogs, there was nothing in this series to suggest cirrhosis.     

Benzodiazepine treatment of panic disorder: a comparison of alprazolam and lorazepam

The antipanic efficacy of alprazolam and lorazepam was evaluated in 48 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder in a double-blind random assignment study. On the basis of rating scale scores, both drugs demonstrated similar efficacy in reducing panic attacks and phobic behavior compared with placebo baseline. The doses required to achieve response were approximately double those required for the treatment of generalized anxiety. These results suggest that most, if not all, benzodiazepines may be effective antipanic drugs at high doses. The implications of these findings for drug treatments of choice for recurrent panic attacks are discussed.     

Contractile speed and EMG changes during fatigue of sustained maximal voluntary contractions

Measurements were made from the human adductor pollicis muscle of force, contractile speed, and electromyographic activity (EMG) before, during, and after maximal isometric voluntary contractions sustained for 60 s. The use of brief test periods of maximal nerve stimulation with single shocks or trains of shocks enabled various muscle mechanical properties to be studied throughout each contraction. Electrical activity was measured after rectification and smoothing of the surface potentials and also by counting the total number of potentials per unit time from a population of motor units using fine wire intramuscular electrodes. During a 60-s maximal voluntary contraction, the force fell by 30-50%. Throughout the experiment the voluntary force matched that produced by supramaximal tetanic nerve stimulation. This indicated that, with sufficient practice, full muscle activation could be maintained by voluntary effort. However, the amplitude of the smoothed, rectifed EMG and the rate of spike counts declined. Since no evidence for neuromuscular block was found, the decline in EMG and spike counts was attributed to a progressive reduction of the neural drive from the central nervous system, despite maintained maximum effort. After the prolonged voluntary contractions twitch duration was prolonged, mainly as a result of slowing in relaxation rate. Twitch summation in unfused tetani increased. Both the maximum rate of relaxation and the time course of force decay declined by 50-70%. Similar changes were seen in both voluntary contractions and in test periods of stimulation. The percentage change in muscle contractile speed measured by these parameters approximately equaled the percentage change in the surface EMG measured simultaneously. It is concluded that 1) during a 60-s sustained maximal voluntary contraction there is a progressive slowing of contraction speed such that the excitation rate required to give maximal force generation is reduced, 2) the simultaneous decline in EMG may be due to a continuous reduction in motoneuron discharge rate, and 3) the EMG decline may not necessarily contribute to force loss.     

Design, synthesis, and testing of insulin hexamer-stabilizing agents

The addition of zinc to insulin solution leads to a long-acting insulin preparation because the zinc stabilizes the less soluble hexameric form of the hormone. It is clear from the crystal structure of dizinc insulin that there is a space at the center of the hexamer, between the two zinc atoms, that could accommodate a small organic molecule. It should thus be possible to design a structure that could further stabilize the insulin hexamer by binding at this site. Computer graphic techniques have been used to design several molecules capable of forming multiple bonds to the six histidine residues surrounding the site. Synthesis and testing of one of these compounds, benzene-1,4-disulfonic acid, show a significant increase in weight-average molecular weight of insulin in solution, and control experiments with related structures suggest that this effect is due to the proposed binding mechanism.