Cholecystokinin-8 increases K-evoked [H]γ-aminobutyric acid release in slices from various brain areas

[³H]γ-Aminobutyric acid (GABA) release was studied in rat brain slices in the absebce or presence of cholecystokinin-8 (CCK-8). [³H]GABA release under the conditions used was Ca²⁺-dependent and insensitive tot he presence of the glial uptake blocker β-alanine. While the basal release of [³H]GABA was not affected by CCK-8, the K⁺-stimulated release of [³H]GABA wasm significantly enhanced by 300 nM of CCK-8 in the caudate putamen, the substantia nigra, the hippocampal formation and the parietofrontal cortex. In the cerebral cortex the CCK-8 enhancement of [³H]GABA release was concentration-dependent and abolished by the CCK_B receptor antagonists PD135,158 (1.0 nM) and L-365,260 (100 nM). A significant counteraction of the CCK-8 action was also found with the CCK_A receptor antagonist L-364,718 (100 nM) but only in concentrations at which both CCK_A and CCK_B receptors are blocked. No CCK-8 effects on [³H]GABA release were observed when tetrodotoxin was superfused 5 min before the K⁺-induced [³H]GABA release. It is suggested that the enhancing actions of CCK-8 on K⁺-stimulated [³H]GABA release is mainly related to an activation of CCK_B receptors.     

The experimental basis of sciatica

Although injuries of the lumbosacral spinal nerve roots in the spinal canal have been recognized as the primary cause of the symptoms of sciatica, the basic pathophysiologic mechanisms of the condition are still poorly understood. It is evident that mechanical deformation of a nerve root is significantly linked to the symptoms of sciatica. It was also recently confirmed experimentally that nucleus pulposus may induce structural and functional changes in adjacent nerve roots, as well as having potential inflammatogenic properties. Probably, the potency of the disc-derived materials has previously not been fully recognized. Recent research is now trying to define which basic pathophysiologic events at the cellular or sub-cellular level are responsible for the nerve root injury. It is to be hoped that the results of such research will provide resources to diagnose and treat patients earlier and more specifically, and that the number of chronic cases should be dramatically reduced.     

Interleukin-1&; and interleukin-6 in the urine,kidney, and bladder of mice inoculated with Escherichia coli

After bladder inoculation of mice using the pyelonephritogenic Escherichia coli strain DS17, urinary interleukin-1α (IL-1α) peaked at 0.5 h post infection (mean 233 pg/ml), interleukin-6 (IL-6) at 2 h (mean 572 pg/ml), and leukocyturia at 4 h, all three persisting for more than 24 h. In the kidneys IL-1α peaked at 2 h, persisted over 24 h (mean 900 – 1,000 pg/ml), and decreased over 2 – 6 days post inoculation to a mean value of 208 pg/ml. Control kidneys showed low IL-1α values. IL-6 in the kidneys peaked at 5 h (mean 9,999 pg/ml) but normalized, i.e., similar to control kidneys, by 48 h (mean 105 pg/ml). A similar cytokine response, but with tenfold lower levels, was found in the bladder tissue. The isogenic P-negative E. coli mutant DS178 elicited lower IL-6 in the kidneys at 5 h, but persisted in higher numbers in the kidneys at 6 days. Bacterial counts and cytokine levels correlated both in the kidneys and in bladder tissue, (r = 0.50 – 0.76, P <0.001). Characterization of the immune response gives a better understanding of the relative importance of different bacterial characteristics for the local inflammatory process and is needed for studies of its pharmacological downregulation. Received May 4, 1995; received in revised form and accepted November 21, 1995     

Histochemical demonstration of mercury in the olfactory system of salmon (Salmo salar L.) following treatments with dietary methylmercuric chloride and dissolved mercuric chloride

The deposition of organic and inorganic mercury compounds was studied histochemically in the salmon Salmo salar L. olfactory system. One group of salmon was given fodder pellets containing methylmercuric chloride (CH₃HgCl, 99 μg Hg/g) for 4 weeks. Other groups of fish were exposed to dissolved mercuric chloride (HgCl₂, 270 μg Hg/liter) for 2, 6, and 12 hr, respectively. In both series of experiments, the radioisotope ²⁰³Hg was included in order to determine the accumulation of mercury in the olfactory system. Gamma-spectrometry showed that both mercury compounds accumulated in the olfactory rosettes and their nerves. Tissue sections from the rosettes and olfactory nerves were subjected to autometallographic silver enhancement, thereby rendering mercury deposits visible for light and electron microscopy. Microscopic analysis demonstrated an intense and comprehensive Hg deposition in the axons and Schwann cells of both methylmercury- and inorganic mercury-exposed fish. On the other hand, the two mercury compounds showed different staining patterns in the sensory epithelium. The silver grains evoked by methylmercury were localized predominantly in lysosome-like inclusions within the receptor cells, while those produced by HgCl₂ exposure were situated mainly along the borders of neighboring cells. The present findings that organic and inorganic mercury compounds were deposited in the olfactory system along its whole length, from the receptor cell apices to the brain, support the electrophysiological results presented elsewhere (Baatrup et al., 1990, Ecotoxicol. Environ. Safety 20, 269–276).     

Omeprazole inhibits growth of cancer cell line of colonic origin

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic thein vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In thesein vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P<0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCI-H716 cell line alone but only at the highest concentration (10^–6M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.     

Distribution of chondroitin 4-sulfate epitopes (2/B/6) in various zones and compartments of articular cartilage in guinea pig osteoarthrosis

We studied changes in the morphology of tibial articular cartilage in early guinea pig osteoarthrosis (OA) at 6 and 12 months of age with quantitative light microscopy, and the distribution of chondroitin-4-sulfate with quantitative ultrastructural immunolabeling, using the 2/B/6 epitope. Labeling was correlated to previous chromatography findings concerning proteoglycan (PG) concentration in animals of the same age. The cell volume fraction had decreased at 12 months in the superficial zone of cartilage with OA (medial condyle) as well as in cartilage without OA (lateral condyle), being lower medially than laterally. The PG concentration differed between the zones and matrix compartments. Medially, a reduction in PG concentration occurred between 6 and 12 months in the interterritorial compartment of the two uppermost zones. Laterally, the concentrations increased. In general, the pericellular PG concentration was higher than the interterritorial in the two uppermost zones. The striking variation in structural and labeling responses in the various zones and compartments indicate a heterogeneous tissue response in guinea pig OA that will probably affect sampling in biochemical analyses of cartilage homogenates and synovial fluid.     

Acute thermal nerve root injury

Summary Bone cement is sometimes used for vertebral body reconstruction following tumor removal. During such procedures, the polymerization of the methyl-metacrylate in the bone cement generates heat. Such temperature increase might cause damage to the nerve roots within the spinal canal. In the present study, pig cauda equina nerve roots were subjected to controlled temperature increases by means of a heat-generating probe. A temperature of 40°C applied for 5 min did not cause any changes in nerve root function. However, 70°C resulted in a complete block of nerve root function within 5 min. Histological nerve fiber damage was seen after exposure to 60°C and 70°C. The present study provides basic knowledge of heat-resistance properties of spinal nerve roots that might be directly applicable as guidelines for safety margins during surgical spine reconstruction procedures using bone cement.     

Dopamine D1 Receptor-mediated Facilitation of GABAergic Neurotransmission in the Rat Strioentopeduncular Pathway and its Modulation by Adenosine A1 Receptor-mediated Mechanisms

By using in vivo microdialysis it was found that one of the main functions of striatal dopamine D₁ receptors is to selectively facilitate GABAergic neurotransmission in the 'direct'strioentopeduncular pathway. D₁ receptors localized in the entopeduncular nucleus were also found to facilitate GABA release. However, results obtained from in vivo microdialysis, in vivo electrochemistry, immunohistochemistry and confocal laser microscopy suggested that entopeduncular D₁ receptors could only be activated under pharmacological conditions. Adenosine A₁ receptors were found to antagonistically modulate the D₁-mediated regulation of the strioentopeduncular pathway. Furthermore, using in situ hybridization D₁ and A₁ receptors were shown to be colocalized in medium-sized striatal neurons. These results show that the strioentopeduncular neuron is a main locus for adenosine-dopamine interactions in the brain.