Circadian rhythm of mitotic activity in the adult gull-tapeworm,Diphyllobothrium dendriticum (cestoda)

Summary The mitotic activity of Diphyllobothrium dendriticum reared in hamsters was studied. The hamsters were 1) fed ad libitum 2) fed in the evening only 3) fed in the morning only, and 4) starved for 24 hours. Starvation of the host drastically reduced mitotic activity in the worms. In all other experiments the mitotic activity showed a circadian periodicity with peaks at 22.00–2.00 hrs and minima at 10.00–18.00 hrs. Worms from hamsters fed in the morning only possibly had a second peak some time after feeding.In the group of hamsters fed in the morning, the mitotic activity of the intestinal mucosa was also investigated. No circadian rhythm was observed.Evidently, availability of nutrients is essential to keep the mitotic activity at a high level. It is assumed, however, that the circadian periodicity also depends on other conditions besides nutrition.This study was supported by Finnish State Council for Science.     

Growth hormone modifies the growth rate of enzyme-altered hepatic foci in male rats treated according to the resistant hepatocyte model

Male and female Wistar rats were given an initiating i.p. injectionof diethylnitrosamine (DEN; 200 mg/kg body wt). Two weeks laterthe rats were given a diet containing 0.02% (w/w) 2-acetylaminofluorene(2-AAF) for 2 weeks. In the middle of the 2-AAF treatment a70% partial hepatectomy (PH) was performed. In order to identifythe pituitary hormone responsible for the previously observedsex difference (male > female) in and influence of ectopicpituitary grafts on focal growth during 2-AAF/PH selection ofenzyme-altered foci, male rats were treated with a continuousinfusion of bovine growth hormone (bGH; 6 µg/h) or ovineprolactin (oPrl; 6 µg/h) by way of osmotic minipumps.Hormonal treatment was started 1 week after initiation and wasfinished 1 week after the 2-AAF selection period. All rats werekilled 6 weeks after initiation and liver sections were stainedfor -ghitamyttransferase. The number of foci/cm² as well asthe area per focus and area ratio (mm² foci/cm² liver section)were calculated. Whereas no significant differences in the numberof foci /cm² were observed between the different groups of rats,bGH treatment of male rats decreased both the area/focus andthe area ratio down to the female level. No significant effectswere seen following oPrl administration when compared with controlmales. In vitro studies of subcellular preparations from theliver lobes obtained at PH showed that the sexually differentiatedN-hydroxy-2-AAF sulfotransferase activity (male > female)in male rats was ‘feminized’, i.e. decreased, bybGH administration, but not by infusion of oPrl. The presentinvestigation strengthens the view of growth hormone as an importantdeterminant of sex differences in chemical carcinogenesis inrat liver, possibly via an influence on carcinogen metabolism.     

Increased metabolism to dihydrodigoxin after intake of a microencapsulated formulation of digoxin

Summary A capsule preparation containing small, enteric-coated granules of digoxin was developed to prevent acid hydrolysis of the drug in the stomach and to diminish the variation in plasma glycoside concentration during the intervals between doses. The absorption and metabolism of tritiated digoxin after a single oral loading dose of this formulation (Formulation C) were compared to those after ingestion of a digoxin solution (Formulation S) by 8 healthy men. Drug concentrations were measured by radioimmunoassay (RIA) and liquid chromatography (LC). The percentage of the digoxin dose excreted in the urine during 72 h, as measured by RIA, was significantly lower after the capsule (20.5±2.0% vs 36.2±3.0% after S, mean±SEM) but total urinary radioactivity after the two treatments was similar (C 35.3±5.2 and S 41.2±2.6%; p>0.05). The discrepancy was mainly due to significantly greater excretion of dihydrodigoxin after the capsule ( 12.8%, range 0–28.6% of the dose) than after the digoxin solution ( 5.4%, range 0–14.5%). Dihydrodigoxin was not measured by the RIA. The recovery of hydrolysis metabolites (LC) was greater during the first 24 h after S (2.3±0.6% vs 0.9±0.3% after C; p<0.05). The peak plasma concentration of digoxin (RIA) was significantly reduced and delayed after intake of C (2.5±0.4 nmol/l at 3.8±0.3 h vs. 8.3±0.8 nmol/l at 0.9±0.1 h after S), and so was the shortening of electromechanical systole at 1.5 h, 2.5 h, and 3 h. Thus, the enteric-coated digoxin preparation delayed the absorption and reduced the hydrolysis of the glycoside, but it also carried the drawback of reducing digoxin availability, mainly because of increased metabolism to dihydrodigoxin.     

On mechanisms of sex differences in chemical carcinogenesis: effects of implantation of ectopic pituitary grafts on the early stages of liver carcinogenesis in the rat

The resistant hepatocyte model was used to investigate the influenceof pituitary factors on the early events of chemical carcinogenesisin rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight,was used as an initiator of enzyme altered foci. Two weeks afterinitiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene(2-AAF) diet for two weeks. Partial hepatectomy (70%) was performedthree weeks after initiation. The rats were killed four to sixweeks after DEN initiation. Sex differences in area/foci aswell as in area ratio (mm² foci/cm² liver section) were foundin liver sections from sexually mature male and female rats( > ) of both the Sprague-Dawley and Wistar strains. Ectopicpituitary grafts (PG: s) implanted under the kidney capsuleof male Wistar rats one week before DEN initiation and removedby unilateral nephrectomy one week after initiation did notinfluence the number or area of enzyme altered foci as comparedwith sham operated male rats. On the other hand, PG:s implantedone week before 2-AAF selection in male Wistar rats and allowedto remain until the rats were killed two weeks after the 2-AAFselection period, decreased the area ratio to a level closeto that of sham operated female rats, whereas no effect on thenumber of enzyme altered foci was found. The results suggestthat the hypothalamo-pitu-itary axis may be involved in theregulation of early stages of liver carcinogenesis.     

Monoclonal antibodies against Vibrio cholerae lipopolysaccharide.

A cell line producing monoclonal antibodies directed against the core region of Vibrio cholerae lipopolysaccharide has been established. These antibodies were inhibited by lipopolysaccharide preparations of both O-group 1 vibrios and some non-O-group 1 vibrios as detected in enzyme-linked immunosorbent assay-inhibition experiments. Coagglutination experiments with monoclonal and polyclonal antibodies adsorbed to protein A-carrying staphylococci were performed. All V. cholerae strains tested, regardless of serotype, were agglutinated when mixed with staphylococci coated with the monoclonal antibodies, whereas staphylococci coated with group-specific (O1) polyclonal antibodies only agglutinated with O-group 1 vibrios.     

Effects of thiopental on resistance vessels in cat skeletal muscle

Barbiturates are used clinically as anaesthetics and to reduce raised intracranial pressure. One side effect is hypotension, usually ascribed to a depression of cardiac contractility, while their effects on the resistance vessels are more controversial: both vasodilation and vasoconstriction have been described. This study analyzes the effects of thiopental on basal vascular tone in the cat skeletal muscle. We found that total resistance increased by almost 20% at low (50mol/l) and decreased down to about 50% of control at high (350 mol/l) plasma concentrations of thiopental. The vasoconstriction dominated in the large arterioles (i.d. >25 m) and the vasodilation in the small arterioles (i.d. <25 m). A dosedependent inhibition of myogenic vascular reactivity (here defined as the maximum resistance increase to a transient rise in transmural pressure) coincided with the vasodilation. Autoregulation of blood flow was depressed by thiopental. During vasoconstriction there was a net transcapillary fluid absorption and during vasodilation a net fluid filtration. The fluid movements could be ascribed to variations in capillary hydrostatic pressure. If applicable to the cerebral circulation these results suggest that thiopental at high plasma concentrations might induce, instead of reduce, interstitial brain oedema.     

Androgen treatment of abdominally obese men

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.