Atropine modulates changes in striatal muscarinic receptor binding sites in barbital abstinence in the rat

We have previously reported that cholinergic mechanisms in the brain are involved in tolerance and physical dependence as expressed in the abstinence after 30–40 weeks forced chronic treatment with barbital to rats (for reviews see Nordberg & Wahlström 1980, 1981a). In the first part of the abstinence period the turnover of acetylcholine (ACh) seems to be increased in different areas of the brain since both decreased content of endogenous ACh and increased biosynthesis of ACh have been recorded (Nordberg & Wahlström 1977, 1979). These changes have been observed at peak abstinence when there is a maximal tolerance to hexobarbital and a maximal number of spontaneous convulsions. Some changes in cholinergic parameters may prevail in late abstinence as illustrated by reduced content of endogenous ACh in the striatum which is still present after 80 days of abstinence (Nordberg & Wahlström 1981b). The muscarinic receptors also undergo changes in the abstinence (Nordberg et al. 1980). In the striatum an increased number of binding sites has been measured on day 0 to 3 in the abstinence. Increases, but with different time courses, are seen also in other brain areas (Nordberg & Wahlström 1982).     

Effect of denervation on acetylcholine synthesizing activity and nicotine-like binding sites in rat hind limb muscles

The acetylcholine synthesizing (ACh-s) activity and the binding of the nicotinic ligands ³H-α-bungarotoxin (α-Btx) and ³H-d-tubocurarine (d-TC) were analysed in rat hind limb muscles 1–32 days after denervation. Muscles of the contralateral leg served as controls. ACh-s activity was considerably lower in tibialis anterior as compared to the extensor digitorum longus and the peroneus longus muscles. After denervation there was a rapid decrease in ACh-s activity in parallel to a considerable increase in α-Btx binding. The binding of d-TC was essentially unchanged following denervation indicating the special characteristics of the newly formed receptors. ACh-s activity can be differentiated into one specific (choline acetyltransferase) and one unspecific component.     

EXTRADURAL MORPHINE: INFLUENCE OF ADRENALINE ADMIXTURE

The influence of the addition of adrenaline on extradural morphineanalgesia and pharmacokinetics was investigated in a double-blindstudy. Morphine 2 mg was administered to 14 patients undergoingthoracotomy. In addition, adrenaline 50 µg added to theextradural solution, was administered to half of the patients,selected randomly. Morphine concentrations in serial plasmaand cerebrospinal fluid (CSF) samples were measured. Postoperativeanalgesia was estimated by determining the requirement for additionalanalgesics. Following extradural administration of plain morphine,the peak morphine concentraions in CSF were 22±5 (SEM)times those in plasma; during the elimination phase the CSFconcentrations exceeded those in plasma by about 150 times.The area under the concentration v. time curve (AUC) was 162±27(SEM) times larger in CSF than in plasma. The admixture of adrenalinewith the extradural morphine increased the individual variabilityin CSF and plasma concentrations. However, compared with theplain morphine group, adrenaline did not significantly increasethe concentrations of morphine in CSF, nor were the morphineconcentrations in plasma significantly decreased. The durationof analgesia was related to the amount of morphine in CSF, thatis AUC (P < 0.05) and peak concentrations of morphine inCSF (P< 0.05).     

Effect of oxotremorine and sodium pentobarbitone on the pharmacokinetics of intravenous tracer doses of radioactive choline

The present study explains for the previous findings that oxotremorine increases and sodium pentobarbitone decreases the initial brain uptake of intravenously injected radioactive choline (3H—Ch). The effects are explained by haemodynamic changes since a corresponding increase and decrease in the plasma concentrations of 3H—Ch were found. This is important to know when 3H—Ch is used for estimation of acetylcholine turnover in the brain. The drugs did not affect the distribution of radioactivity (3H) between plasma and erythrocytes.     

Diurnal fluctuation in striatal choline acetyltransferase activity and strain difference in brain protein content of the rat

Choline acetyltransferase (CAT) activity was measured in two brain regions of rat at different times of the day. A diurnal fluctuation of the CAT activity was found in the striaturn with a high activity during the light period and a low activity during the dark period. In the hippocampus+cortex the CAT activity remained constant. A marked difference in the brain protein content was found between two strains of Sprague-Dawley rats. This finding emphasizes the importance of expressing enzyme activity both per g tissue and g protein especially when comparing data between different research groups.     

Household health surveys in developing countries: could more use be made of them in planning?

Existing health information systems in Eastern Africa are basedon findings in patients visiting hospitals and clinics and onroutine administrative data. They do not reflect the healthsituation and the health care of the underserved, and do not,therefore, generate the information required for planning andprogramming health care for all. Household health surveys arepotentially very useful in filling important information gaps,but past surveys have been poorly adapted to existing healthcare systems; they have been expensive and difficult to replicate,and findings seem to have been rarely used in the planning process.After a brief presentation of current routine reporting, a fewplanning-oriented surveys conducted in Third World countriesare critically reviewed and presented from a planning perspective.It is concluded that household health surveys can be usefulcomponents of health information systems and could be used moreextensively. However, it is important to involve local healthplanners/managers in developing the survey design and the implementationplan, to keep costs at a replicable level and to estimate andreport survey utility and costs.