Early alterations of rat intestinal diamine oxidase activity by azoxymethane,an intestinal carcinogen

Some mutagenic hydrazino compounds are also diamine oxidase inhibitors. Therefore, this interrelationship was studied for the intestinal carcinogen azoxymethane.In vitro, azoxymethane was a very weak inhibitor of rat intestinal diamine oxidase activity.In vivo, after subcutaneous injection of a single dose of azoxymethane, diamine oxidase activity was increased in the duodenum but was mainly inhibited in the colon. Intestinal diamine oxidase activity may then be influenced by regulatory processes induced by azoxymethane rather than by a direct effect.Supported by a grant of the Deutsche Forschungsgemeinschaft Ku 464/2-2.     

AIDS: can we cope?

AIDS has become far more than just another disease; it has become a sensitive political issue, a social and moral problem, a cause of international tensions, a favourite media story and a cause for despair among those who may be infected. Familiarity breeds, if not contempt, then at least complacency; the risk of infection for individuals, even those who are highly sexually active, is often not personalized - people still perceive AIDS as something that happens to other people, not to themselves.     

Neurophysiological evidence of auditory channel anomalies in developmental dysphasia

Steady-state auditory evoked responses to frequency-modulated tones were obtained from normal children and two groups of children with developmental language disorders (developmental dysphasia). Children with predominantly expressive language impairment produced responses not different from normal children, while children with primary receptive language impairment produced responses that were markedly diminished, even absent. This occurred in recordings from either cerebral hemisphere and at mean frequency-modulation depths ranging from +/- 20 to +/- 100 Hz. Pathophysiology of auditory mechanisms concerned with frequency-modulation analysis are particularly associated with receptive developmental language impairment and may underlie associated difficulties in speech perception.     

Ultrastructural features of NPY-containing neurons in the rat striatum

In the present study, we examined the ultrastructure of striatal neurons containing neuropeptide Y (NPY) which were labeled by an immunohistochemical method using peroxidase-conjugated F(ab) fragments in the rat. Each of the 26 neurons identified had a deeply indented oval nucleus. The cytoplasm, which was mainly concentrated at the emergence of the dendrites, contained an abundant Golgi apparatus and a well-developed granular endoplasmic reticulum. Dendrites were poorly branched and rarely exhibited varicosities or dendritic spines. NPY-immunoreactive (Ir) axons were small in diameter and unmyelinated. These features corresponded to a subpopulation of striatal neurons classified as aspiny type IV in previous Golgi studies. Axon terminals forming symmetrical synapses were numerous on the NPY-Ir perikarya and proximal dendrites. On distal NPY-Ir dendrites, synaptic contacts were mainly of the asymmetrical type, suggesting that NPY neurons are contacted by at least 2 categories of afferent fibers. Several NPY-Ir axonal processes and boutons were found to form symmetrical synapses with dendrites, dendritic spines and perikarya belonging to spiny type neurons. These data were consistent with the view that NPY may act as a neurotransmitter of striatal interneurons. Moreover, the frequent observation of NPY axonal processes in the close vicinity of striatal vessels suggested that NPY might also play a role in the control of cerebral vasomotricity. Thirty hours after intranigral injection of 6-hydroxydopamine to induce a degeneration of nigrostriatal dopamine terminals, some characteristic degenerative boutons were observed in close apposition to NPY-Ir cell bodies, suggesting that NPY neurons are under a direct nigrostriatal dopaminergic influence.     

In vitro/in vivo functionality of Catapres-TTS

The in vitro and in vivo functionality of Catapres-TTS, a transdermal therapeutic system that delivers the alpha adrenergic receptor agonist clonidine, is discussed in terms of the drug transport kinetics and resultant plasma drug concentration profiles. The design of Catapres-TTS is presented as an optimization by which the best combination of system performance characteristics is obtained within the inherent limitations of the transdermal drug transport properties and the known pharmacokinetic and pharmacodynamic properties of the drug. Clonidine is a potent antihypertensive agent with a relatively low therapeutic index. For Catapres-TTS, the majority of control over the drug input rate resides within the system, rather than within the skin, which significantly reduces the variability in drug input rate and resulting plasma drug concentration both within and between patients. Moreover, the presence of a rate-control element in the system allows for patterning of the drug release rate. An initial bolus of drug is placed in the contact adhesive layer, where its transport into the skin is not inhibited by the rate control element in the system, for reduction in the time needed to achieve steady state drug input. The selection of the loading dose of drug is described as an optimization between the minimization of the lag time and the maintenance of constant plasma drug concentrations during the crossover period between system applications in chronic therapy.     

Evaluation of the rat tail model for estimating dermal absorption of lindane

Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.