PLATELET-ACTIVATING FACTOR IN THE CNS

Platelet-activating factor (PAF) is a phospholipid synthesized in a variety of cells throughout the body. Platelet-activating factor has been identified in the CNS and has a number of diverse physiological and pathological functions. It has been shown to be a modulator of many CNS processes, ranging from long-term potentiation (LTP) to neuronal differentiation. Excessive levels of PAF appear to play an important role in neuronal cell injury, such as that resulting from ischaemia, inflammation, human immunodeficiency syndrome (HIV) and meningitis. The beneficial effects of PAF receptor antagonists are many and give rise to possible therapeutic strategies for neurotrauma. Copyright © 1996 Elsevier Science Ltd.     

Action of Mitomycin C on Testicular Steroidogenesis and its Probable Mode of Action in Albino Rats

Einfluß von Mitomycin C auf die Steroidgenese im Hoden und ihr möglicher Modus bei Albino-Ratten
Mit Hilfe des Radioimmunassays (Testosteron im Serum) und dem histochemischen Nachweis von dem Schlüsselenzym Δ⁵ 3β hydroxysteroid-dehydrogenase in den Leydig'schen Zwischenzellen nach einer Behandlung mit Mitomycin C wurde die Steroidgenese im Hoden untersucht. Die in vivo Experimente belegen, daß Mitomycin C einen bemerkenswerten Abfall der Serum-Testosteronwerte verursacht im Zusammenhang mit eine signifikanten Reduzierung des Hodengewichtes und des Gewichtes des akzessorischen Geschlechtsdrüsen. In vitro Studien zeigen eine Verminderung der Aktivität von Δ⁵ 3β hydroxysteroiddehydrogenase und der Glukose-6-phosphatdehydrogenase im Hoden nach Zugabe von Mitomycin C in das Inkubationsmedium. Diese Befunde führen zu der Überlegung, daß Mitomycin C die Steroidgenese des Hodens negativ beeinflußt.     

Peptides containing dipropylglycine

Methods for the incorporation of the hindered amino acid 2-amino-2-propyl-pentanoic acid (dipropylglycine, Dpg) into peptides have been investigated. Limitations on the preparation of protected derivatives of Dpg are discussed, and common methods of coupling examined. These methods are not subject to problems when used to link protein amino acids to the amino group of Dpg, but steric hindrance severely limits efficient peptide bond formation by the carboxyl group of Dpg. Only two reagents proved useful in this respect. N-Benzyloxycar-bonyl (Z) Dpg can be coupled through its derivative with 3-hydroxy-4-oxo-3,4-dihydrobenzotriazine; other methods of activation of Z-Dpg tend to lead to formation of 2-benzyloxy-4,4-dipropyloxazolin-5(4H)-one, which resists attack by nucleophiles. 2-Trifluoromethyl-4,4-dipropyloxazolin-5(4H)-one, however, which is readily prepared from N-trifluoroacetyl-Dpg and thionyl chloride, couples cleanly with other amino acids, making it the reagent of choice for introduction of a Dpg residue.     

Hemoglobin Zurich. I. A New Hemoglobin Anomaly Associated with Acute Hemolytic Episodes with Inclusion Bodies after Sulfonamide Therapy

A new abnormal hemoglobin was observed in 15 members over four generations of a large Swiss family and has been termed "Hemoglobin Zürich."The discovery of this hemoglobin was prompted by a severe hemolytic crisisin two members of the family after sulfonamide therapy. During this episode,virtually all erythrocytes and reticulocytes contained a single large inclusionbody which was visible with Giemsa and brilliant cresyl blue stains. Outsidethe hemolytic episode, the erythrocytes revealed no morphologic abnormalities.The results of enzyme studies were all within normal limits. The associationof a hemoglobinopathy with a drug-induced inclusion body anemia withoutany demonstrable enzyme defect is a new entity. The anomalous hemoglobinis inherited as a dominant character and affects both sexes. Thus far, onlythe heterozygous form has been observed.

Submitted on April 9, 1962 Accepted on June 20, 1962     

Clinical Studies with Vincristine

Forty patients with malignant neoplastic disease received vincristine in aneffort to define the toxicity, the tolerated dose, the effect of varying doseschedules, and the antitumor properties. The toxicity of vincristine is doserelated, and the tolerated dose for the weekly schedule is 0.05 mg. per Kg.for the majority of patients. The tolerated dose per unit time is independentof the schedule of administration. The toxic manifestations relate primarilyto the neuromuscular system and the gastrointestinal tract. At the tolerateddose or below, these manifestations are reversible and not accumulative.Hematologic toxicity is rare, and thrombocytosis occurs in some patients.Vincristine produces tumor regression in the majority of the patients withlymphoma where its activity compares favorably with that of the alkylatingagents and vinblastine. There is suggestive evidence that cross-resistance between vincristine and the alkylating agents and between vincristine and vinblastine does not occur.

Accepted on December 28, 1962     

HEMOGLOBIN-OXYGEN AFFINITY IN HYPOPHOSPHATEMIC RICKETS

Abstract. In 14 patients with simple X–linked hypophosphatemic rickets, 5 were below the third percentile in height and 9 were between the third and twenty-fifth percentile. Although the mean serum inorganic phosphorus level was only 2.01±0.65 (normal range for all age groups is 3.8 to 6.0 mg/100 ml), both the mean values for red cell 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were normal at 4.78±1.23 and 1.02±0.17 μmol/ml of red blood cells respectively. Moreover, the mean P₅₀ value was normal at 26.4±0.9 mmHg. These normal oxygen transport data make unlikely any proposal that short stature seen in these patients is secondary to chronic tissue hypoxia. They also indicate that the intra-erythrocytic organic phosphate levels are maintained at normal levels despite profound chronic hypophosphatemia.     

Dofetilide for Atrial Arrhythmias in Congenital Heart Disease: A Multicenter Study

Background: Very little is known about use of the class III antiarrhythmic dofetilide in patients with congenital heart disease (CHD).
Methods: A multicenter retrospective review of experience with dofetilide in CHD patients was undertaken.
Results: Twenty adults with CHD and refractory atrial arrhythmias were treated with dofetilide at four institutions over a 7-year period. Three (15%) experienced adverse effects during in-hospital initiation of dofetilide (two with torsade de pointes, one with excessive QTc prolongation) and were not continued on this therapy. The remaining 17 were discharged taking dofetilide, with either resolved or improved arrhythmia. One was lost to follow-up. Five subsequently discontinued dofetilide due to waning effectiveness, manifest by recurrence of their arrhythmias. Eleven (55%) remained on dofetilide at most recent visit, with a median follow-up of nearly 1 year. Seven of these 11, or 35% of the CHD patients originally started on dofetilide, experienced a complete resolution of their arrhythmia. The remaining four had breakthrough episodes of atrial arrhythmia, but remained on dofetilide. No patient experienced torsade de pointes after the in-hospital initiation period.
Conclusions: Used appropriately, dofetilide appears to be a viable adjunct to catheter-based ablation and alternative pharmacological approaches for the treatment of atrial arrhythmias in adult patients with congenital heart disease.