Microbiological aspects of heat sterilization of drugs

International Journal of Clinical Pharmacy - In order to calculate the minimum sterilization process conditions to obtain the generally accepted sterility level (less than 1·10?6...     

Synthesis and teratogenic action of n-hydroxythalidomide

N-Hydroxythalidomide (1d), a potential metabolite of thalidomide (1a), was synthesized from N-phthalyglutaminic acid anhydride (1b) and O-tetrahydropyraline hydroxylamine, followed by deprotection. The teratogenicity of 1d was studied using the Hen's-Egg-Test model which had been found applicable for 1a. 1d was more teratogenic to chicken embryos compared to 1a. The percentage of teratogenic malformations in the 1d groups was 28-46%, whereas the percentage in the 1a groups was 20-23%. The oxygen protected precursor N-hydroxythalidomide (1c) was less teratogenic (11-15%).     

5-Piperazinylalkyl-2(3H)-oxazolones with neuroleptic activity

A series of new 4-aryl-5-[omega-(4-aryl-1-piperazinyl)alkyl]-2(3H)- oxazolones was synthesized and tested for neuroleptic activity in mice and rats. Several compounds exhibited interesting neuroleptic activity with very low liability to the extrapyramidal side effects. In particular the activity of 4-(4-fluorophenyl)-5-[2-[4-(3,5-dichlorophenyl)-1- piperazinyl]ethyl]-2(3H)-oxazolone (14) was greater than that of butropipazone and fluanisone, while of the same order of that of chlorpromazine; however, the product showed a longer lasting activity and minor ability to produce catalepsy as compared with the reference drugs.     

Distribution of tyrosine-hydroxylase (TH)-immunoreactive neurons in the diencephalon of the pigeon (Columba livia domestica)

The distribution of tyrosine-hydroxylase (TH)-immunoreactive cell bodies and fibers in the diencephalon has been investigated with immunohistological techniques in the pigeon. The results suggest that TH is present in a number of morphologically distinct neuronal systems. Preoptic and hypothalamic TH neurons were subdivided into a medial periventricular and a lateral group. The medial group starts with a rostral collection of small cells in the preoptic region. A significantly larger collection of TH neurons occupies the paraventricular nucleus (PVN) (stratum cellulare internum) and mainly consists of large multipolar cells. Further caudally, the main concentration of cells is in the hypothalamic posteromedial and the periventricular regions of the tuberoinfundibular (arcuate) nucleus. No TH neuron was found in the ventral and lateral parts of the tuberoinfundibular region, suggesting that the prominent tuberoinfundibular dopaminergic system described in mammals is absent in the pigeon. This further substantiated by the relative scarcity of TH immunoreactive fibers and varicosities in the neurohemal zone of the median eminence (ME). The caudalmost components of the medial group appear to be continuous with the large population of TH neurons distributed in the midline of the mesencephalon. Tyrosine-hydroxylase-immunopositive cells have not been found in the paraventricular organ. The lateral group consists of TH neurons loosely arranged in the lateral hypothalamus, including regions of the supraoptic nucleus and hypothalamic posterolateral nucleus. Tyrosine-hydroxylase containing neurons vary widely in size, shape, and dendritic arborization in each diencephalic region. However, it is possible to distinguish two main cell types. Small bipolar neurons with two simple arborizing dendrites were concentrated in the medial periventricular system. The second type of cell is large, multipolar with four to five branching dendrites. This latter cell type occurs mainly in the lateral system and in the PVN. Major fiber bundles containing TH immunoreactivity were identified in the lateral and periventricular hypothalamus. The paraventricular organ and the organum vasculosum laminae terminalis contained the densest arborization of fibers and varicosities. In the ME, dense innervation was found in the subependymal layer. Dense arborizations of TH positive fibers and varicosities were located in the septal nuclei and the paleostriatum augmentatum.     

Demonstration, by the cartographic test, of an unusual reaction to intermittent light stimulation in patients with migraine

Topographic electroencephalography was carried out to study reaction to photic stimulation in 29 normal volunteers, and 12 patients who had presented frequent clinically confirmed migraines for at least 3 years. In the group of migraineurs photic stimulation resulted in an increase in the alpha band power. The difference between the two groups was statistically significant. This reaction to photic stimulation is of help in diagnosis and suggests that a diagnosis and therapeutic orientation might be possible in patients for whom clinical diagnosis is not clear. The specificity of the migraineur's reaction to photic stimulation and its possible origin are discussed.     

Positive sign of the stenocardia syndrome as a criterion of myocardial ischemia during the treadmill test

Diagnostic validity of the criteria of myocardial ischemia in coronary patients exposed to the treadmill test is assessed. The risk of a false diagnosis of coronary insufficiency on the basis of the pain syndrome was 5 times as high as that of diagnosis based on ischemic electrocardiographic ST depression. In subjective assessment of walking tolerance, patients with severe angina were particularly prone to mistakes. Limitations of angina classifications by severity, based on subjective sensations of coronary patients, are considered.