Fluid balance and arterial blood pressure during intracarotid infusions of atrial natriuretic peptide (ANP) in water-deprived goats

The aim of this study was to investigate if atrial natriuretic peptide (ANP) plays a role in the control of water balance in goats and whether ANP affects the increase in mean arterial blood pressure (MAP) which accompanies drinking in water-deprived animals. Bilateral intracarotid infusions were made in female adult goats deprived of water for 48 h. ANP (1.5 micrograms min-1, n = 5, or 4.75 micrograms min-1, n = 5) was infused for 40 min. In control experiments isotonic saline (n = 7) was infused. The goats got access to water 35 min after the start of the infusions. During saline infusions they drank 2.9 +/- 0.4 litres, during the low dose of ANP 1.9 +/- 0.6 litres (n.s. vs saline), and during the high dose of ANP 0.6 +/- 0.2 litres (P less than 0.01 vs saline). Plasma vasopressin concentration did not change during saline infusions until after drinking, when it decreased. The vasopressin concentration increased in one goat after infusion of the low dose of ANP and in two goats after the high dose of ANP. The low dose of ANP caused no change in MAP in four goats, but MAP dropped in the one in which vasopressin concentration increased. MAP fell in all goats infused with the high dose (P less than 0.01), with the largest changes occurring in animals showing increased vasopressin concentration. During the act of drinking a temporary increase of MAP was observed when saline or the low dose of ANP was infused, but this response was attenuated during infusions of the high dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of Francisella tularensis in ulcers of patients with tularemia by PCR.

The diagnosis of human cases of tularemia is usually confirmed by the demonstration of an antibody response to Francisella tularensis, which occurs about 2 weeks after the onset of disease. Due to a high risk of infection in the laboratory, cultivation of the causative agent tends to be avoided. During an outbreak in Sweden, the use of PCR for diagnosing the ulceroglandular form of tularemia was evaluated. Extraction and preparation of F. tularensis DNA from swab samples from the wounds of patients with tularemia involved the use of the nuclease inhibitor guanidine thiocyanate. The DNA was detected by multiplex PCR targeting the 16S rRNA gene and a 17-kDa lipoprotein gene of F. tularensis. In 29 of 40 (73%) patients with serologically confirmed tularemia, F. tularensis DNA was successfully amplified. Considering the limitations of current diagnostic procedures, PCR may become useful for the early diagnosis of tularemia.     

Aldehyde dehydrogenase activities in hepatocyte nodules and hepatocellular carcinomas from Wistar rats

The activities of aldehyde dehydrogenases using benzaldehydeand propionaldehyde as substrates and NADP and NAD as coenzymeswere determined in normal liver, hepatocyte nodules and hepatocellularcarcinomas from male Wistar rats. Hepatocyte nodules were producedby intermittent exposure of rats to 0.05% 2-acetylaminofluoreneor by initiation with diethylnitrosamine followed by selectionusing 2 weeks of dietary exposure to 0.02% 2-acetylaminofluoreneand partial hepatectomy. The activities of propionaldehyde:NAD and benzaldehyde: NADP aldehyde dehydrogenases were increasedin hepatocyte nodules of all types as well as in most hepatocellularcarcinomas. The most prominent elevation of enzyme activitywas found in the cytosol of persistent hepatocyte nodules (35–60times) and some hepatocellular carcinomas (92 times) using benzaldehydeand NADP. The benzaldehyde: NADP aldehyde dehydrogenase activityvaried considerably between different nodules suggesting theexistence of a subpopulation of hepatocyte nodules with veryhigh enzymatic activities. The activity of propionaldehyde:NAD aldehyde dehydrogenase activity as well as of -glutamyltransferasedid not show substantial internodular variations. The activityof benzaldehyde: NADP aldehyde dehydrogenase in individual carcinomasinvestigated in these experiments varied extensively. The datadid not support the idea that all hepatomas had been developedfrom pre-neoplastic nodules with very high activity of thisenzyme.     

Infusion of ornithine-alpha-ketoglutarate in healthy subjects: effects on protein metabolism

Infusion of ornithine-alpha-ketoglutarate (Ornicetil) has been suggested to improve nitrogen balance in trauma patients. Whether this anticatabolic effect is localised to the liver or to skeletal muscle is as yet unknown. Consequently, the splanchnic and leg exchange of amino acids, urea and ammonia were measured in seven healthy non-obese subjects in the basal state and during infusion of ornithine-alpha-ketoglutarate at a rate of 28 mg/min for 150 min. The results demonstrate a six-fold rise in arterial ornithine and an increased uptake by both splanchnic and leg tissues during infusion. The splanchnic uptake of threonine and lysine also increased, while no other alterations were seen in leg amino acid exchange. The arterial urea concentration decreased slightly (-6%, P<0.01) during the infusion in spite of an unchanged urea production from the liver. The ammonia concentration fell by 20% (P<0.05), while glycerol and ketone body concentrations did not change significantly. It is concluded that intravenous infusion of ornithine-alpha-ketoglutarate in healthy subjects does not significantly influence hepatic or skeletal muscle protein metabolism.     

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.     

Randomized trial of oral naproxen or local injection of betamethasone in lateral epicondylitis of the humerus

A randomized pilot study, comparing oral naproxen and a single betamethasone injection, was carried out in 21 patients suffering from lateral epicondylitis of the humerus ("tennis elbow"). The naproxen dosage was 250 mg per day for two weeks. Six milligrams of betamethasone in a long-acting form was given as a local injection. To achieve "blindness," the patients receiving naproxen were also given an injection of saline into the area of maximal tenderness at the epicondyle, while the patients getting the betamethasone-injection were given oral placebo tablets. At a clinical control after two weeks, five of the ten patients receiving naproxen and five of the 11 patients receiving betamethasone injection were improved. Thus, no apparent difference in effect could be noted at an evaluation after two weeks' treatment. No significant side effects were noted with any of the treatments.     

Stereoselective inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by 4-dimethylamino-2,α-dimethylphenethylamine (FLA 336)

Summary The in vitro inhibition by amiflamine [FLA 336(+)] and related compounds of the activity of rat monoamine oxidase (MAO)-A and-B, rat semicarbazide sensitive amine oxidase (SSAO) and human platelet poor plasma benzylamine oxidase was studied. Amiflamine was an MAO-A selective inhibitor, but also inhibits SSAO with both a reversible (competitive, K _i=200 mol/l) and a small time-dependent component which was irreversible in nature. The optical isomer FLA 336(–) was ten times less potent towards MAO-A. However, this compound was much more potent an inhibitor of SSAO (competitive, K _i=4.6 mol/l). The amiflamine metabolites FLA 788(+) and FLA 668(+) inhibited SSAO, but only at concentrations considerably higher than required for MAO-A inhibition. Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones.