No abstract

case ventilatory depression returns. The use of a larger dose of naloxone, given either intravenously or intramuscularly, is being investigated to determine whether the action of naloxone can be usefully prolonged.We thank the midwives, obstetricians, and paediatricians of the University Hospital of Wales for their help and co-operation in the study. There was no significant difference in the peak levels or pattern of enzyme increase. The incidence of cardiac failure and reinfarction was similar in the two groups, but major arrhythmias were less common in those on streptokinase (P <0 05). In the streptokinase group there were 36 minor and six more serious haemorrhagic com- References

Unravelling the complex molecular pathways responsible for motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) remains a persistent challenge. Interest is growing in the potential molecular similarities between these two diseases, with the hope of better understanding disease pathology for the guidance of therapeutic development. The aim of this study was to conduct a comparative analysis of published proteomic studies of ALS and SMA, seeking commonly dysregulated molecules to be prioritized as future therapeutic targets. Fifteen proteins were found to be differentially expressed in two or more proteomic studies of both ALS and SMA, and bioinformatics analysis identified over-representation of proteins known to associate in vesicles and molecular pathways, including metabolism of proteins and vesicle-mediated transport—both of which converge on endoplasmic reticulum (ER)-Golgi trafficking processes. Calreticulin, a calcium-binding chaperone found in the ER, was associated with both pathways and we independently confirm that its expression was decreased in spinal cords from SMA and increased in spinal cords from ALS mice. Together, these findings offer significant insights into potential common targets that may help to guide the development of new therapies for both diseases.

This paper describes a preliminary investigation into the bronchodilator action of khellin in patients with clinical bronchospasm.Khellin is one of the active principles of the plant Ammi visnaga (Linn.), which grows wild in many eastern Mediterranean countries. Simple decoctions of its seeds have apparently been used by the local native populations for generations as a spasmolytic, in particular for the relief of ureteric colic. The recent interest awakened in its possible therapeutic applications has been largely due to the work of Anrep, Barsoum, Kenawy, andMisrahy (1946, 1947); Anrep, Barsoum, and Kenawy (1949).A number of crystalline substances have been isolated from the seeds (Spath andGruber, 1938, 1941a and b). Pharmacologically, the most active of these is khellin, which was first isolated by Mustapha in 1879, and chemically is di-methoxy-methylfurano-chromone. Two principal therapeutic properties have been claimed for this substance. It is said to dilate the coronary arteries and to relax smooth muscle throughout the body, including that of the bronchi. Anrep and others, working on guinea-pig lungs, showed that khellin was a bronchodilator with an activity four to six times greater than that of theophylline-with-ethylenediamine. Weight for weight, however, it was considerably weaker than adrenaline, 4 jmg. of khellin being approximately equivalent to 0.01 ,ug. of adrenaline. They found the drug to be rapidly absorbed by the intramuscular or oral route and stated that its rate of excretion or destruction in the body is slow, so that with continued administration it tends to be cumulative. Kenawy, Barsoum, and Bagoury (1950) have reported favourably on the treatment of bronchial asthma with khellin, and Rosenman, Fishman, Kaplan, Levin, and Katz (1950) have described good results in the treatment of chronic cor pulmonale.We were encouraged to begin this investigation by the dramatic improvement observed in a case with severe clinical bronchospasm, following the oral administration of khellin.* The patient, a man aged 58 years, had been in hospital under the care of one of us for three months with severe continuous asthma, unresponsive to any of the usual remedies. He remained persistently orthopnoeic, wheezing, cyanosed, and distressed, and required oxygen almost continuously. Twenty-four hours after beginning oral khellin, 50 mg. thrice daily, his dyspnoea, orthopnoea, and wheezing disappeared and he lay flat for the first time for many months.* Throughout this work we have used " benecardin " (Benger Laboratories, Ltd.), a presentation of khellin in tablet and ampoule form containing 95%°khellin assayed by a modified colorimetric method.