Sameridine – intrathecal injection in the rat

BACKGROUND: Sameridine is a type of compound with both local anaesthetic and analgesic effects with the clinical intention to be used intrathecally (i.t.) in order to provide both surgical anaesthesia and prolonged postoperative analgesia. Before new drugs are introduced for clinical use, they must be tested for potential toxic effects. METHODS: In the present study sameridine (5 or 10 mg/ml), bupivacaine (5 mg/ml) or saline (9 mg/ml) was injected intrathecally in rats twice, daily (at 07:00 and 19:00), 5 days a week for 2 weeks. Thereafter, the rats were anaesthetised, perfused and the spinal cords were prepared for microscopic investigation. A morphologic method, using light and electron microscopic examination of the cross-section of the spinal cord, was combined with a quantitative morphometric analysis of the number and size of neuronal cells in the dorsal horn as a sensitive indicator of neurotoxicity. Using the laser-Doppler flowmetry technique, the effects of saline and sameridine (1, 5 and 10 mg/ml) on spinal cord blood flow (SCBF) was studied. RESULTS: No signs of neurotoxicity could be seen in any of the animals and no significant differences were seen when comparing the cell number or cell sizes in the groups injected with sameridine, bupivacaine or saline. After i.t. administration of 10 mg/ml sameridine a significant, short-lasting, decrease in SCBF (72% of pre-drug value) was seen. CONCLUSION: In conclusion, our studies do not show any signs of neurotoxic effects of i.t. administration of sameridine in the rat. A transient decrease in SCBF was noted after i.t. injection of sameridine 10 mg/ml.     

Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1–3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6–9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1–3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6–9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.     

Selective monoamine oxidase inhibitors. 4. 4-Aminophenethylamine derivatives with neuron-selective action

Nine 4-aminophenethylamine derivatives were synthesized and tested for monoamine oxidase (MAO) inhibitory effects with particular attention to their selectivity for MAO within monoaminergic neurons in the rat brain. All compounds selectively inhibited the A form of MAO in vitro. Some of the compounds inhibited the MAO within the monoaminergic neurons at much lower doses than those required for inhibition of MAO within other cells in vivo. The most potent compounds in this respect were 4-amino-2-fluoro-alpha-methylphenethylamine (5) and 4-amino-2-chloro-alpha-methylphenethylamine (4).     

DNA fingerprinting of isolates of Staphylococcus aureus from newborns and their contacts

During a study on the epidemiology of Staphylococcus aureus colonization in newborns, mothers, and hospital staff, S. aureus was isolated from 536 of 1,945 specimens. Ninety-three isolates of S. aureus from the three groups of individuals were included in a study to evaluate the potential of DNA fingerprinting for strain differentiation. The 93 isolates were also phage typed and their plasmid profiles were analyzed. Cleavage of DNA with BamHI resulted in 13 different DNA restriction endonuclease band patterns (DNA REBPs), one of which consisted of eight isolates whose DNA was not cleaved with BamHI. The DNAs from these eight isolates were easily cleaved with HindIII. The different DNA REBPs were stable both during in vitro and in vivo growth and allowed strain differentiation within phage groups or types. We could not show any strong association between DNA REBP classes, phage types or groups, and plasmid profiles. Of the 93 isolates, 27 (29.0%) could not be phage typed and 12 (12.9%) lacked plasmids. We therefore conclude that DNA fingerprinting is a powerful tool, in addition to phage typing and plasmid profile analysis, for strain differentiation of S. aureus.     

Estimation of elastic properties in the urethral flow controlling zone by signal analysis of urodynamic pressure/flow data

When urethral flow is treated as a lossless flow through an elastic tube, the relationship between the detrusor pressure and the urinary flow can be related to the elasticity of the flow-controlling zone of the urethra. A recent analytical method of describing urethral elasticity is implemented on a computer. The function p(Q)=p_mo+L_mQ^m is fitted to the recorded pressure/flow data. p(Q) is the detrusor pressure, Q the flow and p_mo, m and L_m parameters. The elastic properties are then obtained as p(A)=p_mo+K_nAⁿ, where p(A) is the static pressure, A the cross-sectional area of the flow-controlling zone and n and K_n calculated parameters. The urodynamic methods used and the computer implementation of the analytical method are described. In obstructed and unobstructed men without neurological symptoms, the elastic properties could be estimated in 94 per cent of the micturitions. The method makes it possible to describe urethral flow properties with Griffiths' model in a standardised way and compare results obtained by different investigators. It is recommended for quantification of urethral obstruction in research and for assessment of borderline cases of obstruction in clinical practice. deceased     

Pressure measurement techniques in urodynamic investigations

It is apparent that the use of accurate pressure measurement techniques is essential for the outcome of urodynamic investigations. The aim of this paper is to estimate the demands on urodynamic pressure measurements and to review the properties of various techniques used. For the infused catheter technique, the dynamic properties are very much dependent on the complicance of the infusion system. With optimal infusion, the bandwidth and the pressure rise rate seem to be sufficient for most applications. Intraluminal microtransducers have a high bandwidth, but a certain fiber optic transducer cannot accurately measure mechanical pressure in the collapsed urethra. The principal differences in measuring hydrostatic pressure between the infused catheter technique and microtransducers should be observed. Flexion artefacts are a problem when measuring urethral pressure profiles. Newly developed transducers may offer a solution to this problem.