Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol or thioridazine

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by itself in the striatum or nucleus accumbens, inhibited the ability of clozapine to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The clozapine-induced increase in DA in the frontal cortex was not blocked by scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in that the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite its strong muscarinic antagonist properties, does not produce full blockade of muscarinic receptors in vivo in the striatum. The interaction of clozapine with the cholinergic system in the striatum could be relevant to its lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.     

Modifications of reward expectation-related neuronal activity during learning in primate striatum

This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.     

InP/InGaAsP double-heterostructure optoelectronic switch

The double-heterostructure optoelectronic switch (DOES), fabricated in the InP/InGaAsP material system, is demonstrated. The functional characteristics and operational parameters exhibit a lower switching voltage (≈1.8 V) and a higher on-state holding current (≈20 mA) than found in either the Si/SiGe- or GaAs/AlGaAs-based DOES of comparable structures and doping levels. In the on-state, optical emission is observed in a manner analogous to a light emitting diode. However, enhanced optical emission is observed when the device is biased in the regime of negative differential resistance     

Diterpenoids

Our aim was to review the results and to investigate the prognosis in a prospective study of aggressive surgical treatment in 186 patients (59% women, 41% men, age 18 to 65 years) treated during the past 9 1/2 years by conventional laying open of the fistula (n = 71), endorectal advancement flap repair (n = 89) and by fistulectomy without internal sphincterotomy (n = 37). 54 (29%) patients had intersphincteric, 57 (30.5%) transsphincteric, 10 (5.5%) suprasphincteric, 37 (20%) low rectovaginal and 28 (15%) had complex fistulas without internal opening. Four sphincter saving techniques were performed by the high and fistulas (n = 89) with primary occlusion of the intraanal ostium and endorectal mucosal flap (n = 29), endorectal advancement flap (n = 41), anodermal flap (n = 8) and transperineal repair with levator interposition (n = 11). Postoperatively 18 cases (20.2%) of suture leakage occurred, 27% in the mucosal flap group, 17.6% in the advancement flap group, 12.5% in the anodermal group, and 27% in the transperineal group. A complete primary healing of perianal wounds was noted in 73% of the patients within 6 months. The presence of rectal disease (n = 77) did not adversely influence the rate and duration of healing. Persistent or recurrent fistula occurs in 29 patients (15.6%), 22% in the sphincter saving group, 4% in the intersphincteric group and 32% in the complex type of fistulas. Disturbance of continence was observed in 9 patients (4.8%). Postoperatively, there was no significant change in resting anal pressure and maximum voluntary conctraction pressure in any fistula group (n = 104). CONCLUSION: The presented clinical and functional long term results of patients with Crohn's fistulas underline the importance of experience in the treatment of perianal fistula disease. A successful treatment depends primarily on an aggressive therapeutic strategy and the appropriate method of operation.     

Bovine longissimus muscle tenderness as affected by postmortem aging time, animal age and sex

Strip loins were removed from 10 bulls and 10 steers ～14 mo old and from 10 cows ≥ 44 mo. Samples were removed at 3, 7, 14, and 28 days postmortem. Shear-force values were measured. Sensory evaluation was done by a 15-member trained panel. Animal age and postmortem aging time had more influence on tenderness attributes than did sex of the animal. Increased postmortem aging time improved tenderness attributes regardless of sex or age.     

Enhanced post-receptor insulin effects in women following dehydroepiandrosterone infusion

While treatment for the neonate continues to be challenging, current technical advances offer more options. Before the 1980s chronic dialysis was technically so difficult for neonates and infants that most considered it impossible; in the 1990s renal replacement therapy is a viable choice. The purpose of this article is neither to advocate active intervention nor passive supportive care, but to help the reader consider questions frequently faced when deciding what to do for a neonate with end-stage renal disease (ESRD). Today ethical issues are tied closely to health care reform, so this bioethical dilemma has only begun. As health care reform addresses benefits of care, the bioethical dilemmas raised by neonates with ESRD will need to carefully considered.     

Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).     

Modelling cortical cataractogenesis. XXIX. Calpain proteolysis of lens fodrin in cataract

The relation between cataract and calpain proteolysis of lens fodrin was studied in two systems: elevated glucose (55.6 mM, diabetic model), and cytochalasin D (CD, 10(-2) mM, actin depolymerization-induced opacity model). Glucose treatment (48 h) caused a visible opaque layer and enzyme leakage, with a concomitant accumulation of ([Ca2+]i) around the lens equatorial cortex. CD caused both earlier and greater opacity and enzyme leakage than glucose. Lens fodrin digestion occurred in parallel with the timing and extent of calcium elevation. A calpain inhibitor peptide (CIP, 10(-2) mM) reduced the proteolysis of fodrin, opacity, and enzyme leakage in glucose-treated lenses but only partially retarded them in CD-treated lenses. These results suggest a mechanism in which calpain proteolysis of fodrin is a critical event in lens damage during opacification of cortical cataract.     

Hypoxic pulmonary vasoconstriction is impaired in rats with nitrofen-induced congenital diaphragmatic hernia

The aim of this study was to determine the efficacy and toxicity of topotecan administered as a 21-day continuous intravenous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas. 26 previously untreated patients with advanced or metastatic pancreatic adenocarcinoma received topotecan at a dose of 0.5 mg/m2/day or 0.6 mg/m2/day as a continuous intravenous infusion for 21 days. Courses were repeated every 28 days. 26 patients were assessable for response and toxicity on an intent-to-treat basis. The initial 8 patients at a starting dose of 0.6 mg/m2/day experienced unacceptable myelosuppression and dose delays. The subsequent 18 patients, therefore began therapy at a dose of 0.5 mg/m2/day. The major toxicity of topotecan at this dose and schedule was myelosuppression, which was reversible and non-cumulative. There were no complete responses and two partial responses for a total response rate of 8% (95% confidence interval, 1-25%). Response durations were 17 and 45 weeks. Stable disease was seen in 3 patients. The median time to progression for all patients was 8 weeks and the median survival was 20 weeks. Topotecan given as a 21-day continuous intravenous infusion has a similar response rate and median survival to our previously reported study of the 5-day short infusion regimen in pancreatic carcinoma.