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A Post

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Automated spectrophotometric assay of cefazolin.

An automated, stability-indicating, UV spectrophotometric assay for cefazolin is presented. The method employs a reaction with hydroxylamine and derives its stability-indicating power through comparison of reacted and unreacted aliquots of the sample. A double-probe sampling procedure is used. Good agreement with microbiological assays is obtained, and the coefficient of variation is about 1%.

Autoanalysis↗

Plasma protein binding of drugs as a function of age in adult human subjects.

The intent of this study was to determine what influence, if any, increasing age has on the binding of drugs by plasma proteins. Plasma from healthy subjects ranging in age from 21 to 94 years was used. The binding of phenytoin (diphenylhydantoin) (acid), penicillin G potassium (benzylpenicillin potassium), and phenobarbituric acid was determined by equilibrium dialysis of 14C-labeled compounds. No differences were found in total protein concentration; however, albumin was reduced in subjects over 50 years of age. Plasma binding of each drug studied was not related to age; this finding suggests that age per se is not a factor in the binding of drugs by plasma proteins.

Adult↗

Semiautomated turbidimetric microbiological assay for determination of cefazolin.

The Autoturb System, a semiautomated system for photometric bioassay, was used to determine cefazolin content. Suitable conditions for the assay using Streptococcus faecalis ATCC 10541 as the indicator organism included a medium pH of 6.0 to 7.0 and an incubation time of 3 to 3.5 h at 36 C. Multiple independent assays of samples from a common batch showed the test to be highly reproducible. Accuracy of the turbidimetric assay was evaluated by comparing data obtained from a chemical (hydroxylamine) and a biological (disk diffusion) assay. The available data show the turbidimetric assay to be a rapid, accurate, and reproducible method for determining the biological activity of cefazolin samples.

Autoanalysis↗

Repetitive transcranial magnetic stimulation induces active coping strategies and attenuates the neuroendocrine stress response in rats.

The effects of repetitive transcranial magnetic stimulation (rTMS) on various brain functions were investigated in adult male Wistar rats. The stimulation parameters were adjusted according to the results of accurate computer-assisted, magnetic resonance imaging-based reconstructions of the current density distributions induced by rTMS in the rat and human brain, ensuring comparable stimulation patterns in both cases. The animals were subjected to daily rTMS-treatment (three trains of 20 Hz; 2.5 s) for 8 weeks from the age of 4 weeks on. In the forced swim test these rats showed a more active stress coping strategy than the control rats. This was accompanied by a significantly attenuated stress-induced elevation of plasma ACTH concentrations. Pituitary changes accounting for the attenuation were ruled out by the corticotropin-releasing hormone test. Baseline concentrations of ACTH and corticosterone were indistinguishable in the two groups. No changes were found in the anxiety-related behavior of the rats on the elevated plus-maze or in behavior during the social interaction test. Accordingly, the binding characteristics of the benzodiazepine agonist [(3)H]flunitrazepam at the benzodiazepine/gamma-aminobutyric acid type A receptor complex were similar in the rTMS and control groups. In summary, chronic rTMS treatment of frontal brain regions in rats resulted in a change in coping strategy that was accompanied by an attenuated neuroendocrine response to stress, thus revealing parallels to the effects of antidepressant drug treatment.

Adaptation, Psychological↗

Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms?

Potential therapeutic properties of repetitive transcranial magnetic stimulation (rTMS) have been suggested in several psychiatric disorders such as depression, mania, obsessive-compulsive disorder, posttraumatic stress disorder and schizophrenia. By inducing electric currents in brain tissue via a time-varying strong magnetic field, rTMS has the potential to either directly or trans-synaptically modulate neuronal circuits thought to be dysfunctional in these psychiatric disorders. However, in order to optimize rTMS for therapeutic use, it is necessary to understand the neurobiological mechanisms involved, particularly the nature of the changes induced and the brain regions affected. Compared to the growing number of clinical studies on its putative therapeutic properties, the studies on the basic mechanisms of rTMS are surprisingly scarce. rTMS currently still awaits clinical routine administration although,there is compelling evidence that it causes changes in neuronal circuits as reflected by behavioural changes and decreases in the activity of the hypothalamic-pituitary-adrenocortical system. Both alterations suggest regional changes in neurotransmitter/neuromodulator release, transsynaptic efficiency, signaling pathways and in gene transcription. Together, these changes are, in part, reminiscent of those accompanying antidepressant drugs.

Animals↗

Pulmonary surfactant protein C containing lipid films at the air-water interface as a model for the surface of lung alveoli.

The pulmonary surfactant lines as a complex monolayer of lipids and proteins the alveolar epithelial surface. The monolayer dynamically adapts the surface tension of this interface to the varying surface areas during inhalation and exhalation. Its presence in the alveoli is thus a prerequisite for a proper lung function. The lipid moiety represents about 90% of the surfactant and contains mainly dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG). The surfactant proteins involved in the surface tension adaption are called SP-A, SP-B and SP-C. The aim of the present investigation is to analyse the properties of monolayer films made from pure SP-C and from mixtures of DPPC, DPPG and SP-C in order to mimic the surfactant monolayer with minimal compositional requirement. Pressure-area diagrams were taken. Ellipsometric measurements at the air-water interface of a Langmuir film balance allowed measurement of the changes in monolayer thickness upon compression. Isotherms of pure SP-C monolayers exhibit a plateau between 22 and 25 mN/m. A further plateau is reached at higher compression. Structures of the monolayer formed during compression are reversible during expansion. Together with ellipsometric data which show a stepwise increase in film thickness (coverage) during compression, we conclude that pure SP-C films rearrange reversibly into multilayers of homogenous thickness. Lipid monolayers collapse locally and irreversibly if films are compressed to approximately 0.4 nm2/molecule. In contrast, mixed DPPG/SP-C monolayers with less than 5 mol% protein collapse in a controlled and reversible way. The pressure-area diagrams exhibit a plateau at 20 mN/m, indicating partial demixing of SP-C and DPPG.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗