Fish oil treatment and apolipoprotein(a).

Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross-over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels.     

G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells

Summary Differentiated human leukemia (HL 60) cells contain high numbers of receptors for the chemotactic factors, N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and complement component 5a (C5a), both coupled to pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Agonist activation of either receptor stimulated binding of the GTP analog, guanosine 5-[-thio]triphosphate (GTP[S]), to membrane G proteins and by a similar extent in a non-additive manner. The possible interaction of the two receptors was studied by measuring agonist binding to one receptor in the presence of the other receptor agonist. fMet-Leu-Phe and C5a had no effects on [¹²⁵I]C5a and fMet-Leu-[³H]Phe receptor binding, respectively, when studied in the absence of regulatory ligands. Similarly, the inhibitory effects of NaCl and GDP on agonist receptor binding were not altered in the presence of the other receptor agonist. In contrast, in the presence of the GTP analogs, GTP[S] and guanosine 5-[,-imino] triphosphate, fMet-Leu-Phe and C5a reduced the binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe, respectively, in a concentration-dependent manner. The potencies of the GTP analogs to inhibit binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe was increased about 3-fold by fMet-Leu-Phe and C5a, respectively. The data presented suggest that fMet-Leu-Phe and C5a receptors share the same G protein pool in membranes of HL 60 cells and that activation of these G proteins by one of the two receptors decreases the availability of G proteins for the other receptor. Correspondence to T. Wieland at the above address     

Effect of photocorrosion on cadmium sulfide suspensions applied in animal inhalation studies with CdS particles

Cadmium sulfide aerosol (90 g Cd/m³) was generated from an aqueous suspension for 12 weeks and the ratio of Cd⁺⁺/Cd_total in the suspension and the resulting aerosol was determined. After 4 weeks the concentration of Cd⁺⁺ in the suspension and the aerosol leveled off at 43.5±11.4% and 35.8±6.8%, respectively. Therefore, lung tumors in rats observed after inhalation exposure to such CdS aerosols (Glaser et al. 1990) may have been caused not only by the effect of CdS but also by the influence of inhaled Cd⁺⁺ or CdSO₄. The contribution of CdS particles to the observed lung tumor rate depends on the bioavailability of CdS retained in the lungs. The photochemical decay of CdS in aqueous suspensions only occurred when exposed to light and adjusting the suspension up to pH 3 did not increase the decomposition rate of CdS. Ethanolic suspensions of CdS are much more stable than aqueous ones and experiments with suspensions kept under shield gases showed that the decay of CdS is not dependent on oxygen.     

Stoff und Applikationsart beim Drogenkonsum Jugendlicher

Zusammenfassung In einer Stichprobe von 382 schweren Drogenkonsumenten wurden Art und Ausmass des Drogenkonsums unter Berücksichtigung der Applikationsart der Stoffe erfragt und die Angaben einer Faktorenanalyse unterworfen. Es bildeten sich drei Faktoren mit den Kurzbezeichnungen «intravenös applizierte illegale Drogen», «oral applizierte illegale Drogen» und «oral applizierte Medikamente». Dies weist darauf hin, dass sich «intravenös spritzen» von den übrigen Applikationsarten eindeutig unterscheidet und dass die Definitionen des Betäubungsmittelgesetzes ein starkes Kriterium für die Einstellung der Drogenkonsumenten den Stoffen gegenüber ist. Pharmakologische Gesichtspunkte und solche der subjektiven Wirkung der Stoffe erlangen daneben kaum sichtbare Bedeutung.

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Drugs and their modes of application — a factor analytic inquiry of drug abuse

Summary In a sample of 382 heavy users mode and extent of drug abuse were inquired. Factor analysis of the data gave three factors named i.v. applicated illegal drugs, oral applicated illegal drugs and oral applicated medicaments for short. Results show that attitudes of the drug users towards their drugs are strongly influenced by the mode of application and the definitions of the drug laws, whereas pharmacological aspects and subjective effects have hardly any demonstrable importance.

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Drogues et leurs modes d'application — une enquête concernant la consommation abusive de drogues utilisant l'analyse factorielle

Résumé Une enquête sur mode et quantité de l'abus de drogues a été faite dans un échantillon de 382 graves consommateurs de drogues. L'analyse factorielle des données mène à trois facteurs abbréviés: «drogues illégales appliquées i.v.», «drogues illégales appliquées per os» et «médicaments appliqués per os». En regardant ces résultats on peut dire que les attitudes des consommateurs envers les drogues sont tout d'abord influencées par la mode d'application et les définitions des lois concernant les narcotiques, pendant que des points de vue pharmacologiques et les effects subjectifs n'ont peu d'importance.

     

Electron microscopic localization of nitric oxide I synthase in the organ of Corti of the guinea pig

Nitric oxide synthase (NOS) activity has been detected previously in the mammalian cochlea at a light microscopic level. Here we present results of electron microscopic analysis for post-embedding immunoreactivity of neural-type NOS I in the cochlea of the guinea pig. Strong enzyme immunoreactivity was identified in the cytoplasm of inner and outer hair cells. Gold-labeled NOS I antibodies were mainly located in electron-dense areas of the cytoplasm, whereas electron-lucent regions of the receptor cells were nearly free from any immunoreactivity. In both types of hair cells anti-NOS I antibodies were also visible in the cuticular plates, hair bundles and nuclei. Further ultrastructural analysis revealed that the submembranous cisternae of the outer hair cells were nearly free from any reaction product, demonstrating that the whole cytoplasm of this hair cell was not immunoreactive. Other NOS I immunoreactivity was identified in the cuticular plates of the inner and outer pillar cells and in the cytoskeletal elements located in the apical parts of Deiter cells, forming the lamina reticularis or in cytoskeletal-containing regions in basal Deiter cells. Anti-NOS antibodies were visible in the nuclei of various cell types. Our findings suggest that nitric oxide produced by NO I synthase in the organ of Corti may act as a modulator of hair cell physiology during the processes of signal transduction with frequence selectivity.     

Alteration of loosely bound calcium in the guinea pig organ of Corti after treatment with diltiazem as calcium channel blocker

After oral administration of the organic calcium channel blocker diltiazem to guinea pigs for 7 days, calcium ions were precipitated with potassium antimonate in the cochleae. The spatial distribution of the precipitates was studied by energy-filtering transmission electron microscopy and the amount of the ultrastructural reaction products formed was determined semiquantitatively by an image processing system. Compared with untreated control ears, the number of the formed precipitates was reduced drastically in the inner hair cells after diltiazem treatment. In addition, electron microscopic analysis revealed that the number of calcium precipitates attached at the basolateral membrane of the outer hair cells was clearly reduced when compared with untreated control specimens. A large number of histochemical reaction products could be identified in the basilar membrane and were also observed in the untreated control specimens. The spatial distribution of the calcium precipitates in the lamina reticularis was not affected by diltiazem treatment and calcium precipitates could be identified within different cell membranes. The technique used was considered to be helpful for identifying calcium channels ultrastructurally in intact undissected tissues and to support light microscopic analyses and patch-clamp electrophysiological measurements.     

Use of electron spectroscopic imaging to determine element composition of the melanin granules in the stria vascularis of the guinea pig

Electron spectroscopic imaging (ESI) was used to analyze the element content of melanin granules in the stria vascularis seen in ultrathin sections of Spurr-embedded cochleae of the guinea pig. To determine element composition, ESI images were taken at different ionization edges, and non-specific background signals were subtracted digitally by an image processing system. The presence of calcium and nitrogen in the melanin granules could be demonstrated clearly. The calcium identified in the melanin granules was then compared with the spatial distributions of calcium binding sites after the application of an antimonate precipitation method, which was used to localize loosely bound calcium. Despite a high calcium concentration within the granules, only very small single scattered calcium precipitates could be detected between these structures as compared with the amount of calcium precipitates attached to the plasma membrane or located within the cell nuclei. The nearly complete absence of precipitates within the melanin granules after the application of antimonate suggests differences in calcium binding and mobility involved in various physiological processes of ion balance regulation within the stria vascularis. Received: 14 October 1997 / Accepted: 11 February 1998     

Evidence that Tamoxifen Preserves Bone Density in Late Postmenopausal Women with Breast Cancer

Tamoxifen, which is used for treating breast cancer, exhibits estrogenic and antiestrogenic characteristics, depending on the tissue. In the human breast it acts as an antiestrogen, whereas estrogenic effects have been reported on endometrium and bone. The purpose of this study was to determine whether tamoxifen (TAM) prevents bone loss in elderly, postmenopausal women. Bone mineral density of the lumbar spine (SBD) was measured in elderly women (at least 10 years after menopause) 5 years after stage I or II breast cancer (n=111). The results showed that SBD in untreated patients (n=74) was significantly lower (p0.05) than SBD in patients (n=37) treated with TAM over 5 years. In a subgroup of patients (n=24) with positive estrogen receptor status, changes in SBD 12 months after discontinuation of 5-year TAM therapy were measured and compared with the changes of extended TAM treatment over a sixth year. Twelve months after withdrawal of 5-year TAM medication (n