Enhancement of altered hepatic foci in rat liver and inhibition of intercellular communication in vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin

Male Sprague-Dawley rats dosed with N-nitrosodiethylamine (NDEA)24 h after two-thirds partial hepatectomy were treated withthe pyrethroid insecticides fenvalerate, flucythrinate or cypermethrinin the diet: for 20 weeks. Altered hepatic foci were analyzedby quantitative stereology from paraffin-embedded sections stainedfor     

Seasonal variation of lead uptake in the earthworm Lumbricus terrestris and the influence of soil liming and acidification

The influence of seasonal temperature variations and liming and acidification of the soil on lead uptake in juveniles and adults of the earthworm species Lumbricus terrestris L. was studied by enclosing specimens for up to five months in net bags provided with lead-contaminated, sandy soil. Lead concentrations were analyzed in the pharynx, gizzard, muscles, seminal vesicles and cerebral ganglion. Lead distribution in whole animals was assessed after an injection of ²⁰³Pb. The lead concentrations of the tissues were mostly linearly correlated with the soil concentrations, which ranged from <0.5 to 310 mg/kg, and the highest concentrations were generally found in the ganglion. The effects on lead concentrations in tissues of lowered soil pH from 5.6 to 5.1 or raised to 5.9 were insignificant, though more lead became allocated to muscles than to ganglion when pH was lowered. The lead uptake was strongly dependent on the ambient temperature, especially in the muscles, and the concentrations were reduced by 50% or more during the cold spell in the winter season, presumably as a consequence of a low feeding activity. Though juveniles seemed more prone to take up lead, the concentrations were not significantly higher than those in adults during the winter period. The observations are discussed in the light of the use of earthworms in standardized programs for environmental hazard assessment, especially with respect to species and tissue selection.     

Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons.

Short-lasting application (10 min) of tachykinin neuropeptides evokes long-lasting (>24 h) modulation of N-methyl-D-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral-root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist D-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output.     

Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ

Lung function, smoking, age and mortality data in 158 adult severe alpha₁-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV₁ value was significantly associated with increased mortality (p < 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV₁ values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV₁ values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV₁ levels (p = 0.008) and higher mortality (p < 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV₁ level were not statistically significant (p = 0.9 and p>0.25, respectively). Cross-sectional analysis of the initial FEV₁ values indicated a significant decline (p < 0.005) of FEV₁ with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV₁ rates of decline in 80 cases with follow-up FEV₁ measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.     

Hematogenous infection after knee arthroplasty

Twenty-five hematogenously infected knee arthroplasties in 20 patients (17 with rheumatoid arthritis and 3 with arthrosis) were followed for 3 years. Staphylococcus aureus was the major infecting organism. Three patients with four arthroplasties died of sepsis. Two patients had removal of the arthroplasty, one of which resulted in an above-the-knee amputation. Four out of five arthrodeses fused. Two knees healed after early debridement and two healed without surgery. Ten knees had successful revision arthroplasty.

Rheumatoid arthritis and constrained prostheses increase the risk of hematogenous infection. Any infection and especially cutaneous lesions in a patient with a knee arthroplasty should be treated vigorously.     

Interaction of lectins with human T lymphocytes mitogenic properties,inhibitory effects,binding to the cell membrane and to isolated surface glycopeptides

The mode of interaction of twelve lectins with human T lymphocytes was investigated. In order to establish possible differences between mitogenic and nonmitogenic lectins, they were studied for their capacity to induce or inhibit DNA synthesis. Their interaction with intact T cells was studied by immunofluorescence and ⁵¹Cr release. Further, lectins conjugated to Sepharose were investigated with regard to their capacity to bind surface glycopeptides from T cell lysates. Operationally, the lectins could be divided into three groups: (a) mitogenic lectins; (b) lectins inhibitory for lymphocyte mitogenesis as induced by leucoagglutinin (La) from Phaseolus vulgaris; and (c) nonmitogenic lectins which were noninhibitory in this La system. Six lectins were nonmitogenic. For two or possibly three of these, lack of mitogenicity was due to complete or partial failure to bind to the lymphocytes. This explanation could not account for lack of mitogenicity of the other three nonmitogenic lectins. Only two of the lectins utilized inhibited La-induced mitogenesis. However, when the lectins were compared with regard to their capacity to bind surface glycopeptides from T cell lysates, important differences between mitogenic and nonmitogenic lectins were seen. As revealed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and autoradiography, the mitogenic lectins bound a larger number of surface glycopeptides (15–20) than the nonmitogenic lectins (3–10). More importantly, five distinct glycopeptides (gp 135 K, 125 K, 105 K, 95 K and 43 K) were bound by all mitogenic lectins but not by the nonmitogenic lectins. It remains to be established whether these glycopeptides are present on the T cells which are susceptible to the mitogenic action of the lectins and whether it is the interaction of the lectins with one or several of them which triggers mitogenicity.     

Expression of the CD44 receptor in the blood vessel system: an experimental study in rat

The CD44 receptor is a transmembrane glycoprotein expressed on a variety of cells like endothelial, epithelial and smooth muscle cells. This molecule has many important functions, e.g. in cell-cell and cell-matrix interactions and signal transduction. The main ligand for CD44 is hyaluronan (HYA). HYA is a glycosaminoglycan with structural and cell biological properties. The localization of HYA in the vessel wall of arteries and veins in the healthy adult and newborn rat has been described earlier. In this study the occurrence of the CD44 receptor was investigated in the same vessels and compared to the localization of HYA. Both CD44 and its ligand showed an increased expression in the vessel wall of newborn rats compared to that of adult rats. Although HYA is abundant in the adventitia of adult rats, virtually no expression of CD44 was observed. Our results indicate that the CD44 receptor expression is increased during the stage of maturation of the vessel tree whereas the CD44 receptor is less needed by HYA in the healthy vessel wall.     

Blood Lymphocyte Proliferation Response to Pollen Extract as a Monitor of Immunotherapy

In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.     

Effects of lithium on water intake and renal concentrating ability in rats with vasopressin-deficient diabetes insipidus (Brattleboro strain)

Male and female Long Evan rats and Brattleboro rats with ADH-deficient diabetes insipidus were treated with lithium administered in the diet for 12 weeks. The plasma lithium level was about 1 mmol/l in all groups. Lithium caused polydipsia and polyuria and lowering of renal concentrating ability in normal rats. In rats with ADH deficiency lithium tended to increase water intake, but did not influence spontaneous urine osmolality or maximal urine osmolality during water deprivation. The results indicate that the renal concentrating defect caused by lithium in rats can be explained by ADH-blockade as the only mechanism. However, there is circumstantial evidence that lithium in addition may stimulate thirst mechanisms by an ADH-independent action.