Synthesis of tumor necrosis factor α (TNF-α) by human monocytes in vitro

Research Institute of Hematology and Blood Transfusion, Ministry of Health of the Belorussian SSR, Minsk. Institute of Experimental Hematology and Biotechnology, All-Union Hematologic Scientific Center, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. A. Zotikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 9, pp. 287–289, September, 1991.     

Cytostatic effect of different strains of Bacillus Calmette-Guérin on human bladder cancer cells in vitro alone and in combination with mitomycin C and Interferon-α

Summary The cytostatic activity of five Bacillus Calmette-Guérin (BCG) strains (Pasteur, Evans, Tice, RIVM and Connaught) on human transitional cell cancer T24 cells was examined. A striking effect was noted even in 2-day cultures, and the effect was more pronounced when the cells were incubated for 5 days with different BCG strains alone. The concentrations needed were about the same as those used in clinical practice (10⁹ colonyforming units of Pasteur strain in 100 ml buffered saline solution). Combination with mitomycin C or interferon--2b potentiated the cytostatic effect. A slight difference in cytostatic activity between different BCG strains was found.     

Increased senile plaques without microglia in Alzheimer's disease

Summary To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controls were investigated immunohistochemically by a double-labeling method using anti--protein antiserum and anti-ferritin antibody, which is a recently reported microglia marker. In addition, a quantitative analysis was performed. The senile plaques which appeared initially in the nondemented aged controls consisted of a diffuse type without any amyloid cores and these were found in the group aged 50–59 years. The great majority of them were found to contain no ferritin-positive microglia. The number and proportion (percentage) of microglia-containing diffuse plaques increased with age. Classical and compact plaques began to appear in the brains of the group aged 70 years and over, and practically all of them contained microglia. These results suggest that microglia are not associated with initial plaque formation, but correlate with amyloid core formation. In AD, the most prominent feature was that the diffuse plaques, which contained either no or only a few ferritin-positive microglia, increased markedly.Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

The ONG capsular lens,report of 100 implantations

This Capsular Lens (ONG, type IV, to be called O.C.L.) has been developed for routinely performed extracapsular cataract extraction with lens implantation. The fundamental surgical procedure was based on continuing experience with the bimanual aspiration-irrigation technique and system developed by the author in 1971. The biomechanical properties of the asymmetric partly flexible, haptic loops are designed to give tensionfree fixation in two capsular pockets. The plano-anterior position of the lens ensures well-defined irido-lenticular clearance and proper alignment of the convex side with the posterior capsule. Consequently no iridectomy or iridotomy is needed for proper aqueous flow.     

Dibromoethane effects on the induction of γ-glutamyl-transpeptidase positive foci in rat liver

The initiating and promoting activities of 1,2-dibromoethane in rat liver were investigated using the enzyme-altered foci bioassay. The incidence of -glutamyl-transpeptidase (GGT)-positive foci was used as an early histochemical marker for hepatocarcinogenesis. To determine the initiating activity of 1,2-dibromoethane, the halogenated hydrocarbon was administered orally in corn oil as single or multiple doses (60 or 120 mg/kg) either before or after partial hepatectomy. The animals were then given a promoting regimen of 500 ppm phenobarbital in their drinking water. No increase in the incidence of GGT-positive foci was observed in any of the 1,2-dibromoethane initiation groups. The tumor promoting activity of 1,2-dibromoethane was determined in partially hepatectomized rats which were initiated with N-nitrosodiethylamine (30 mg/kg; po), and one week later were administered 1,2-dibromoethane (10 or 30 mg/kg) orally in corn oil five times weekly for 8 weeks. Control groups receiving sham hepatectomy or no initiator were also treated with the halogenated hydrocarbon five times weekly. Only in those animals which received partial hepatectomy, N-nitrosodiethylamine initiation, and 1,2-dibromoethane was the incidence of GGT-positive foci significantly increased. These results do not support significant initiator activity of 1,2-dibromoethane in rat liver, but do indicate that 1,2-dibromoethane possesses promoter activity which may contribute to its carcinogenic activity.     

Y-maze behavior in the mouse after morphine or an enkephalin analog

The mechanism of clonidine-induced hyperphagia and weight gain in monkeys was studied in 11 Stumptail macaques. Clonidine induced a significant increase in food intake over baseline levels and a significant weight gain after the 3-day treatment period. Both changes induced by clonidine were antagonized by the ₂-noradrenergic antagonist yohimbine, but not by prazosin, an ₂-noradrenergic antagonist. These results suggest that clonidine-induced hyperphagia and weight gain in monkeys are mediated through ₂-noradrenergic receptors.     

Physiologic model for the pharmacokinetics of 2′deoxycoformycin in normal and leukemic mice

A flow-limited physiologic mathematical model has been developed to describe the time course of 2deoxycoformycin (2dCF) concentrations in the plasma and tissues of mice following iv and ip doses. Urinary excretion is modeled as a linear process involving filtration and secretion, since kidney clearance exceeded estimated glomerular filtration rate. Intracellular binding is described as the sum of linear nonspecific binding plus strong saturable binding to adenosine deaminase. Pharmacokinetic parameters are determined by a sequential optimization scheme in which each tissue is studied by means of a hybrid model. The model has been used to predict pharmacokinetic behaviour of 2dCF in both normal and leukemic mice, and model simulations are compared with published data.     

Effect of hexachlorobenzene on enzymes of the steroid metabolism in rat liver

Adult female Wistar rats were fed with a diet containing 0.05% hexachlorobenzene. On the 60th day of this treatment the specific activities of NADPH: ⁴-3-oxosteroid-5-reductase and the 3-hydroxysteroid dehydrogenases in rat liver microsomes were diminished compared to control rats. The cytoplasmatic 5-reduction was higher in HCB treated rats than in control rats. These alterations of the steroid metabolism lead to increased formation of 5-H-steroids which are known to be inducers of the porphyrin biosynthesis.

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Zusammenfassung Erwachsene weibliche Wistar-Ratten wurden mit 0.05% Hexachlorbenzol enthaltendem Futter ernährt. Am 60. Tag dieser Behandlung waren die spezifischen Aktivitäten der NADPH: ⁴-3-oxosteroid-5-Reduktase und der 3-Hydroxysteroid-Dehydrogenasen in Lebermikrosomen, verglichen mit Kontroll-Ratten, vermindert. Die cytoplasmatische 5-Reduktion war bei HCB-behandelten Ratten höher als bei Kontroll-Ratten. Diese Veränderungen des Steroidmetabolismus führen zu vermehrter Bildung von 5-H-Steroiden, von denen bekannt ist, daß sie Induktoren der Porphyrin-Biosynthese sind.

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Abbreviations HCB Hexachlorobenzene - 5-DHT 5-Dihydrotestosterone (17-hydroxy-5-androstan-3-one) - 5-DHT 5-dihydrotestosterone (17-hydroxy-5-androstan-3-one) Dedicated to Prof. Dr. Hj. Staudinger on occasion of his 65th birthday     

Absorption of β-methyl-digoxin determined after a single dose and under steady state conditions

Summary Single doses of -methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum^® or Lanitop^® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of -methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with -methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop^® ampoules or oral treatment with Lanitop^® tablets. For a standard daily dose of 0.2 mg -methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.