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Biomedical subjects

P A Johansson

Publications and source records attributed to P A Johansson.

15 recordsLinked to original sources

Blood-CSF barrier function in the rat embryo.

Blood-cerebrospinal fluid (CSF) barrier function and expansion of the ventricular system were investigated in embryonic rats (E12-18). Permeability markers (sucrose and inulin) were injected intraperitoneally and concentrations measured in plasma and CSF at two sites (lateral and 4th ventricles) after 1 h. Total protein concentrations were also measured. CSF/plasma concentration ratios for endogenous protein were stable at approximately 20% at E14-18 and subsequently declined. In contrast, ratios for sucrose (100%) and inulin (40%) were highest at the earliest ages studied (E13-14) and then decreased substantially. Between E13 and E16 the volume of the lateral ventricles increased over three-fold. Decreasing CSF/plasma concentration ratios for small, passively diffusing molecules during embryonic development may not reflect changes in permeability. Instead, increasing volume of distribution appears to be important in this decline. The intracellular presence of a small marker (3000 Da biotin-dextranamine) in plexus epithelial cells following intraperitoneal injection indicates a transcellular route of transfer. Ultrastructural evidence confirmed that choroid plexus tight junctions are impermeable to small molecules at least as early as E15, indicating the blood-CSF barrier is morphologically and functionally mature early in embryonic development. Comparison of two albumins (human and bovine) showed that transfer of human albumin (surrogate for endogenous protein) was 4-5 times greater than bovine, indicating selective blood-to-CSF transfer. The number of plexus epithelial cells immunopositive for endogenous plasma protein increased in parallel with increases in total protein content of the expanding ventricular system. Results suggest that different transcellular mechanisms for protein and small molecule transfer are operating across the embryonic blood-CSF interface.

Albumins↗

Aquaporin-1 in the choroid plexuses of developing mammalian brain.

The normal brain develops within a well-controlled stable internal "milieu" protected by specialised mechanisms referred to collectively as blood-brain barriers. A fundamental feature of this environment is the control of water flow in and out of the developing brain. Because of limited vascularisation of the immature brain, choroid plexuses, via the cerebrospinal fluid, have been proposed as the main route of fluid exchange between the blood and brain interfaces. We describe the temporal expression and appearance of aquaporin-1 (AQP1) which is important for water transfer across adult choroid plexuses. AQP1 expression was studied in rat embryos using real time reverse transcription/polymerase chain reaction. mRNA for AQP1 was present in rat brain at embryonic day 12 (E12) one day before the protein was detectable in the fourth ventricular choroid plexus (the first plexus to appear); its relative levels increased at E13-E14 when more AQP1-immunoreactive cells appeared in all plexuses. The presence of AQP1 was determined immunocytochemically in five different mammalian species (rat, mouse, human, sheep and opossum) in all four choroid plexuses from their earliest appearance. In all five species studied, the appearance of AQP1 immunoreactivity followed the same developmental sequence: the fourth, lateral and, finally, third ventricular choroid plexus. The stage of choroid plexus development when AQP1 was first detected in all five species and in all four choroid plexuses corresponded to the transition between Stages I and II. The cellular localisation of AQP1 in all choroid plexuses, as soon as it was detectable, had the characteristic apical membrane distribution previously described in the adult; a basolateral membrane localisation was also observed.

Animals↗

Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of l-DOPA-induced dyskinesia.

Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of l-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with l-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic l-DOPA treatment affected opioid receptor binding in both the basal ganglia and the cerebral cortex, producing changes that were both structure- and receptor-type specific, and closely related to the motor response elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with l-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to l-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.

Animals↗

Rapid spectrophotometric pH measurements based on the dual-wavelength technique.

A spectrophotometric method for the measurement of pH in solutions of lidocaine hydrochloride (Xylocaine) for injection is presented. 4-Nitrophenol is used as an indicator for determinations of pH in the range 6.5-7.0. The method was found to be faster than the conventional potentiometric method, mainly due to the utilization of a computer-controlled photodiode array spectrophotometer for the measurements. A further advantage with the spectrophotometric method is that errors arising from varying liquid junction potentials are avoided.

Journal Article↗

Long-term oral treatment with high doses of verapamil in lone atrial fibrillation.

It has earlier been shown that verapamil given intravenously or orally in sufficiently high single doses, may result in regular ventricular rhythm in patients with atrial fibrillation. We have analyzed whether this effect of verapamil can be utilized in long-term oral treatment. Eleven patients with lone atrial fibrillation were studied. Verapamil was given in gradually increasing doses from 40 mg three times a day to 320 mg three times a day, either alone or in combination with digoxin. Resting ECG was recorded and supine and standing blood pressures were measured on each dose level. When the patients were treated with verapamil alone, only a slight decrease in heart rate was noted, while during combined treatment with verapamil and digoxin a more marked heart rate decrease occurred with increasing doses of verapamil. The variation coefficient of the RR interval, a sign of ventricular regularity, decreased during verapamil treatment regardless of whether or not digoxin was also taken. A dose-dependent blood pressure decrease was noted during verapamil treatment. Side effects were common and led to discontinuation of the attempted protocol in all patients. Three patients were unexpectedly converted to stable sinus rhythm. Five patients improved subjectively, with a marked decrease in the sensation of palpitations during intake of increasing doses of verapamil. The study indicates that chronic oral treatment with verapamil may sometimes relieve the subjective sensation of palpitations in patients with atrial fibrillation. Side effects do, however limit the value of this mode of treatment in the majority of patients.

Administration, Oral↗

A simple rapid method for quantifying microorganisms by their metabolic activity when bound to a specific adsorbent.

A simple rapid assay for microorganisms is described. An adsorbent capable of binding microbial cells is deposited in a disposable plastic syringe. A sample to be analyzed is drawn into the syringe and the number of attached microorganisms is calculated from their ability to produce metabolites. The smallest number of yeast cells in a given sample was 50,000. Each analysis takes 2.5 h.

Concanavalin A↗