Phototoxicity of tetracyclines as related to singlet oxygen production and uptake by polymorphonuclear leukocytes

The photo-induced singlet oxygen production of six tetracyclines was measured as tryptophan degradation. Demethylchlortetracycline was the most efficient singlet oxygen producer followed by doxycycline. The least efficient producer was minocycline. Doxycycline, however, was the most potent inducer of photodamage to polymorphonuclear leukocytes (PMNLs) followed by demethylchlortetracycline. Accordingly, the singlet oxygen production during irradiation did not correlate with the induction of photodamage to the PMNLs. However, the uptake of doxycycline by the cells was 3 times higher than that of demethylchlortetracycline, and the tetracycline-induced photodamage to the PMNLs correlated with the product of singlet oxygen production during irradiation and the drug uptake by the cells.     

Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.     

Operative versus non-operative treatment of recent injuries to the ligaments of the knee. A prospective randomized study

Two hundred consecutively seen patients who had an injury to either the anterior cruciate ligament or the medial collateral ligament, or both, were randomly allocated to treatment by either conservative or a surgical regimen. Injuries to the medial collateral ligament could not be demonstrated to benefit from surgical treatment in any respect--with or without surgery the results were excellent. With injuries to the anterior cruciate ligament, recovery was more rapid without surgery but otherwise the results differed between the groups in only one respect: the pivot-shift test was more often positive after conservative treatment. The results were good in both treatment groups even though most of the patients who had an injury of the anterior cruciate ligament were somewhat less pleased with the outcome after a period of time.     

Nutritional dwarfing: is it a consequence of disturbed psychosocial functioning?

Nutritional dwarfing refers to a condition in which maladaptive eating patterns play a primary role in poor linear growth and delayed pubertal development. The present controlled study assesses whether nutritionally dwarfed children and adolescents differ in their psychosocial adjustment from healthy children and adolescents of comparable height in ways that might account for their undernutrition. Children with nutritional dwarfing (n = 16) were compared by standardized questionnaires with a short-stature (ie, heights below the fifth percentile) control group composed of children and adolescents with constitutional growth delay and/or familial short stature (n = 31). Scores on a self-report screening questionnaire for eating disorders did not differentiate the groups. Moreover, the vast majority of nutritionally dwarfed patients expressed a desire to have a heavier physical appearance. Whereas the groups were generally similar in self-perceptions of domain-specific competencies and positive psychosocial adjustment, the parents of nutritionally dwarfed children reported that their children showed significantly fewer externalized behavior problems. These findings suggest the existence of an eating disturbance that compromises growth in childhood and/or adolescence which, unlike anorexia nervosa, is not associated with evidence of psychopathology.     

Oesophageal ulcerations and plasma levels of different alprenolol salts: potential implications for the clinic

The ulcerogenic effect of five different salts of alprenolol were tested against placebo in a porcine oesophageal test model. The salts with high water solubility, such as the hydrochloride and the fumarate, gave rise to the highest plasma concentrations of alprenolol and evoked serious oesophageal lesions, while the salts with low solubility-the benzoate, maleate and sebacate-had no irritative effect on the oesophagus. The plasma levels of alprenolol were much higher following administration of alprenolol hydrochloride in the oesophagus than after an identical intraduodenal dose of the same salt possibly because of the avoidance of the first-pass degradation during oesophageal absorption.