Stable Anticonvulsant Action of Benzodiazepines During Development in Rats

Abstract— The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg^?1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0·1 and 0·02 mg kg^?1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.     

Relative Immunogenicity and Tolerogenicity of Individual Regions or Segments of the MHC

Mixed lymphocyte culture (MIX) reactivity, induction of cytotoxicity in vitro, survival of skin allografts, and induction of neonatal transplantation tolerance were compared in mice of the strain combinations differing in the entire H-2 complex or in individual segments of it. The results showed that antigenic products of the K end of the H-2 complex were more immunogenic and also more resistant to tolerance induction than the products of the D end of H-2. I-region products that elicited transplantation reactions of variable strength, depending on the detection system, were relatively easier to overcome in tolerance induction and could, at least in some combinations, contribute to tolerance induction across the barrier represented by the products of the K region of the H-2 complex.     

Enterostomy in Patients with Primary Neuropathic Amyloidosis

Three patients with primary neuropathic amyloidosis are reported. They were all almost totally disabled by either diarrhea and incontinentia alvi or obstipation. In all three patients enterostomies were tried as a palliative treatment and the results of the operations have been very promising.     

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.