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T Honkanen

Publications and source records attributed to T Honkanen.

At least 19 recordsLinked to original sources
PubMed2004

Variation in natural selection for growth and phlorotannins in the brown alga Fucus vesiculosus.

Directional selection for plant traits associated with resistance to herbivory tends to eliminate genetic variation in such traits. On the other hand, balancing selection arising from trade-offs between resistance and growth or spatially variable selection acts against the elimination of genetic variation. We explore both the amount of genetic variation and variability of natural selection for growth and concentration of phenolic secondary compounds, phlorotannins, in the brown alga Fucus vesiculosus. We measured variation in selection at two growing depths and two levels of nutrient availability in algae that had faced two kinds of past growing environments. Genetic variation was low for growth but high for phlorotannins. The form and strength of selection for both focal traits depended on the past growing environment of the algae. We found strong directional selection for growth rate in algae previously subjected to higher ultraviolet radiation, but not in algae previously subjected to higher nutrient availability. Stabilizing selection for growth occurred especially in the deep growing environment. Selection for phlorotannins was generally weak, but in some past-environment-current-environment combinations we detected either directional selection against phlorotannins or stabilizing selection. Thus, phlorotannins are not selectively neutral but affect the fitness of F. vesiculosus. In particular, there may be a fitness cost of producing phlorotannins, but the realization of such a cost varies from one environment to another. Genetic correlations between selective environments were high for growth but nonexistent for phlorotannins, emphasizing the high phenotypic plasticity of phlorotannin production. The highly heterogeneous selection, including directional, stabilizing, and spatially variable selection as well as temporal change in selection due to responses to past environmental conditions, probably maintains a high amount of genetic variation in phlorotannins. Such variation provides the potential for rapid evolutionary response of phlorotannins under directional selection.

Analysis of Variance↗
PubMed2001

Epidemiology of three cases of severe diphtheria in Finnish patients with low antitoxin antibody levels.

During the 1990-1998 diphtheria epidemic in the newly independent states of the former Soviet Union, more than 150,000 infections and 5,000 deaths occurred. During this period, more than 10 million trips were made from Finland to Russia or vice versa. This resulted in only 10 cases of diphtheria in Finland. There was no secondary spread to healthcare workers or other close contacts. Three patients had severe respiratory tract diphtheria. All three were middle-aged men who had made a short visit to Russia, during which time they had intimate contact with local women. These findings suggest diphtheria was transmitted mainly by direct saliva contact. All patients with severe diphtheria had a non-protective level of antitoxin antibodies during the first days of the disease. Only the patient whose antibody titre rose rapidly to a protective level (>1 IU/ml) had an uncomplicated recovery. The other two, one of whom died, had myocarditis and severe polyneuropathy.

Adult↗
PubMed2000

Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin.

OBJECTIVE: To study the effects of possible interactions between levosimendan and warfarin on pharmacokinetics and pharmacodynamics. Furthermore, the effects of levosimendan on blood coagulation were investigated. METHODS: Open, randomised cross-over design with two treatment phases was used. During one phase, levosimendan (0.5 mg four times daily) was given orally to ten healthy subjects for 9 days. On the fourth treatment day with levosimendan, a single oral dose of warfarin (25 mg) was given. Pharmacokinetic parameters of levosimendan from the third and fourth treatment days were compared with each other. During the other treatment phase the subjects received only a single dose of warfarin. Pharmacokinetic parameters of warfarin alone were compared with those determined after concomitant administration of levosimendan. Changes in blood coagulation parameters were evaluated after levosimendan and warfarin alone and after concomitant administration. RESULTS: Warfarin did not change the pharmacokinetics of levosimendan. The distribution volume of warfarin was higher and elimination half-life shorter after concomitant levosimendan administration than after warfarin alone. However, concomitant levosimendan administration did not potentiate the effects of warfarin on blood coagulation assessed using activated partial thromboplastin time (APTT) and thromboplastin time (TT-SPA). Levosimendan alone for 3 days did not change APTT or TT-SPA values. There were no changes in the protein binding of levosimendan or warfarin upon concomitant administration. Continuous treatment with oral levosimendan caused headache, which was probably due to cerebral vasodilation. CONCLUSIONS: Concomitant levosimendan administration did not potentiate the effect of warfarin on blood coagulation after a single dose. Levosimendan itself had no effects on blood coagulation.

Adult↗
PubMed1998

The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan.

Itraconazole is a potent inhibitor of CYP3A4 isoenzyme and it can cause clinically significant interactions with some other drugs. Levosimendan is a new calcium-sensitizing drug intended for congestive heart failure. We aimed to study possible interactions of itraconazole with levosimendan in healthy volunteers. Twelve healthy male volunteers were included into a randomized, double-blind, two-phase crossover study. A wash-out period of 4 weeks was held between the phases. The subjects were given orally itraconazole 200 mg or placebo daily for 5 days. On the fifth day, they received a single oral dose of 2 mg of levosimendan. Levosimendan plasma concentrations were determined up to 12 hours and ECG, heart rate, and blood pressure followed-up to 8 hours after intake of levosimendan. Itraconazole had no significant effects on the pharmacokinetic parameters of levosimendan. Neither were there any differences in heart rate, PQ-, QTc- or QRS intervals between the placebo and itraconazole phases. The systolic blood pressure was decreased slightly more (p < 0.05) during the itraconazole phase than during the placebo phase. In conclusion, because the potent CYP3A4 inhibitor itraconazole had no significant pharmacokinetic interaction with levosimendan, interactions with CYP3A4 inhibitor, and oral levosimendan are unlikely.

Adult↗
PubMed1997

Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.

Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. In this study the possible interactions between levosimendan and ethanol in human have been studied. Twelve healthy male volunteers were included in this double-blind, randomized, cross-over study. The study consisted of three treatment periods: levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and ethanol concentrations were collected for 8 h after the dosing. To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for subjective assessment of performance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the pharmacokinetics of levosimendan except the volume of distribution of central compartment which was decreased. Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.

Adult↗
PubMed1996

Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients.

OBJECTIVE: To compare the safety, efficacy, tolerability and duration of the antihypertensive effect of an ACE-inhibitor spirapril 3 mg or 6 mg in elderly (> or = 60 y) hypertensive patients in a multicentre, observational, double-blind randomised study. METHODS: After a four-week placebo period, 39 patients were randomised to six weeks of treatment with spirapril 3 mg and 47 patients with spirapril 6 mg. RESULTS: In the sitting position the mean (SD) decrease in systolic blood pressure (SBP) was 12(15) mmHg (95% confidence interval 7 to 17 mmHg) and in diastolic blood pressure (DBP) 10(7) mmHg (8 to 12 mmHg) in the 3-mg group and 10(13) mmHg (6 to 14 mmHg) and 9(7) mmHg (7 to 11 mmHg), respectively, in the 6-mg group (P < 0.001 compared to placebo period in both groups). Spirapril 3 mg and 6 mg produced DBP < or = 90 mmHg or a fall > or = 10 mmHg in 53% and 51% of the patients, respectively. DBP was < or = 90 mmHg in 36% and SBP < or = 160 mmHg in 67% of the patients taking 3 mg and in 26% and 63% of the patients taking 6 mg spirapril. The most commonly reported adverse effects were cough (13-17%), dizziness, headache and insomnia. A trend to a more frequent adverse effects was observed in patients receiving spirapril 6 mg. Spirapril was both cholesterol- and glucose-neutral. CONCLUSIONS: According to our study, spirapril 3mg seems to be a suitable starting dose for the treatment of hypertension in the elderly patients.

Aged↗
PubMed1995

Reproducibility of angiotensin converting enzyme inhibitor induced cough: a double-blind randomised study.

1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.

Adult↗
PubMed1994

Oral induction and consolidation of acute myeloid leukemia with etoposide, 6-thioguanine, and idarubicin (ETI) in elderly patients: a randomized comparison with 5-day TAD. Finnish Leukemia Group.

In order to study the efficacy of an oral induction and consolidation regimen in the treatment of acute myeloid leukemia (AML) in elderly patients assessed not to tolerate full-scale intensive chemotherapy, 51 patients over 65 years of age with newly diagnosed AML were randomized to receive two cycles of either totally oral ETI (25 patients) or conventional 5-day TAD (26 patients). The median age of the patients was 73 years, range 65-87 years. Thirty-eight patients had de novo AML and the remaining patients AML subsequent to myelodysplastic syndrome ((n = 11) or treatment related AML (n = 2)). ETI consisted of etoposide 80 mg/m2 and thioguanine 100 mg/m2 twice a day on days 1-5, and idarubicin 15 mg/m2 on days 1-3, all given orally. TAD consisted of oral thioguanine and i.v. cytarabine, both in the dose of 100 mg/m2 twice a day on days 1-5, and daunorubicin 60 mg/m2 on day 5. The maintenance treatment was daily oral mercaptopurine 70 mg/m2 and weekly oral methotrexate 12 mg/m2. In the ETI group complete remission (CR) was achieved in six patients after the first cycle and in nine more patients after the second cycle. The CR rate was 15/25 = 60%. The corresponding figures for the TAD group were four and two remissions, CR rate 6/26 = 23% (p = 0.007). The survival was significantly longer in the ETI arm (p = 0.042). The median survival was 9.9 months in the ETI group and 3.7 months in the TAD group. There were no significant differences in the side effects between the two arms. In conclusion, the totally oral ETI regimen resulted in a significantly higher remission rate and longer survival than the 5-day TAD regimen in elderly patients with AML, with no more toxicity.

Acute Disease↗
PubMed1992

Comparative study of the olfactory epithelium of the three-spined stickleback (Gasterosteus aculeatus) and the nine-spined stickleback (Pungitius pungitius).

The olfactory epithelium of the three-spined stickleback (Gasterosteus aculeatus) and the nine-spined stickleback (Pungitius pungitius) has been studied with a conventional histochemical and a novel immunological staining technique. In both species, the sensory epithelium is arranged in folds separated by non-sensory epithelial tissue. In the nine-spined stickleback, intrinsic folds consisting of non-sensory cells are found in the apical part of the sensory epithelium where they divide the surface of the sensory epithelium into small islets. These non-sensory cells are non-ciliated, flattened and piled on top of each other; they contain numerous electron-translucent vesicles. The intrinsic folds are absent from the sensory epithelium of the three-spined stickleback. In both species, axons of receptor cells form a layer of fibers in the sensory epithelium immediately above the basal cells. In the three-spined stickleback, thick branches of the olfactory nerve are frequently found in this layer. These branches are only occasionally observed in the sensory epithelium of the nine-spined stickleback. Thus, the three-spined stickleback and the nine-spined stickleback show considerable differences in the organization of the sensory regions of the olfactory epithelium.

Animals↗
PubMed1992

Venous thrombosis: a controlled study on the performance of scintigraphy with 99Tcm-HMPAO-labelled platelets versus venography.

Thirty-three patients with symptoms and signs of a deep venous thrombosis (DVT) were examined by contrast venography and radionuclide imaging with 99Tcm-hexamethylpropyleneamineoxime (99Tcm-HMPAO)-labelled autologous platelets. There were 13 patients on heparin therapy and 20 without anticoagulation during the scintigraphy. Scintigraphy consisted of blood pool imaging at 5 to 20 min and accumulation imaging at 2, 4-6 and 18-24 h. In scintigraphy a positive finding was either a defect of radioactivity in the immediate blood pool phase or a hot spot indicative of accumulation of platelets in later phases. Fifteen out of 23 patients positive by venography were also positive by scintigraphy. Five of the eight false negative patients were on heparin treatment, two probably had DVT which were not quite fresh. The venography negative patients were also negative on scintigraphy. Nine out of 12 patients without anticoagulation had positive platelet accumulation compared with two out of 11 patients on heparin therapy. This difference was statistically significant (P less than 0.025). The sensitivity and specificity of platelet scintigraphy were 65 and 100%, respectively, in all patients and 83 and 100% in patients without anticoagulation. Our results suggest that scintigraphy with 99Tcm-HMPAO-labelled platelets is a useful alternative in diagnosing DVT in patients in whom a standard contrast X-ray venograph is contraindicated or otherwise unsuccessful.

Adult↗
PubMed1991

An immunocytochemical study of the development of the olfactory system in the three-spined stickleback (Gasterosteus aculeatus L., Teleostei).

Antisera against a variety of substances have been found to produce an identical immunoreaction in the developing olfactory system of a teleost, the three-spined stickleback (Gasterosteus aculeatus). The label is localized in the olfactory placode, the olfactory nerve and those parts of the secondary olfactory tracts which constitute the dorsal descending fascicles and the ventral descending fibers of the medial olfactory tract. The label was first detected 3 days after fertilization (3D) in the olfactory placode where labeled supporting cells were observed. At 4D, the label was observed at the site of the developing olfactory bulbs. At 7D, the olfactory placode lost the direct contact with the brain and the labeled olfactory nerve became visible. At the same time, the medial olfactory tract emerged from the bulbs, and contacts with cells in the nucleus of the terminal nerve were observed. The development of the medial olfactory tract proceeded caudally, and by the end of 10D, the olfactory tract reached the periventricular hypothalamus. Pre-absorption of the antisera with the respective antigens did not abolish the capacity of the antisera to produce the label. The immunoreaction is thus not specific for the antigens against which the antisera have been raised. Yet the label produced by the immunoreaction is an extremely reliable marker for the primary olfactory tract, and the only existing marker by which secondary olfactory tracts can be visualized.

Animals↗
PubMed1990

An immunocytochemical study of the olfactory projections in the three-spined stickleback, Gasterosteus aculeatus, L.

The distribution of olfactory fibers in the brain of the three-spined stickleback was visualized by means of immunohistochemistry. The labeling of the olfactory fibers was produced by serum containing antibodies against somatostatin-14. Olfactory fibers were observed entering the olfactory bulbs, where they terminated in the glomerular layer or collected into fascicles that coursed through the bulbs into the telencephalon without participating in the formation of the glomerules. In the telencephalon the fascicles, which belonged to the medial olfactory tract, formed two fiber systems: ventral descending fibers and dorsal descending fibers. The ventral descending fibers could be followed through the ventral telencephalon to the vicinity of the lateral tuberal nucleus. The dorsal descending fibers coursed via the anterior commissure to the posterior part of the telencephalon. Part of the postcommissural fibers of the dorsal descending system coursed to the posterior zone of the area dorsalis telencephali while others left the telencephalon via the medial forebrain bundle and could be followed to the periventricular hypothalamus. Some axons formed synaptic contacts with unlabeled cell bodies in the nucleus of the terminal nerve which, in this species, is situated immediately behind the bulbs. In addition, an extensive terminal field associated with the dorsal descending fibers was found in the ventromedial aspects of the telencephalon. It is unlikely that the labeling represents immunoreactive somatostatin-14 because: 1) the labeling persisted after the absorption of the antiserum with synthetic somatostatin-14; 2) antiserum against somatostatin-14 from another manufacturer did not have this labeling property; and 3) the production of the absorbable labeling depended on the choice of fixative whereas the production of the unabsorbable labeling did not.

Animals↗
PubMed1989

High serum erythropoietin levels are normalized during treatment of congestive heart failure with enalapril.

Eighteen patients with dilated cardiomyopathy (three female, mean age 57 years), were treated for 48 weeks with enalapril added to digoxin and diuretic therapy for congestive heart failure of New York Heart Association (NYHA) functional class II (three patients). III (eight patients) and IV (seven patients), respectively. Serum levels of erythropoietin (EPO) were raised at the start (37 +/- 12.8 pmol 1(-1); mean +/- SD) and were normalized during enalapril treatment (17.5 +/- 9.9 pmol 1(-1) at 48 weeks; P less than 0.001). Serum EPO correlated at the start with NYHA functional class (r = 0.68; P less than 0.05). Normalization of elevated serum EPO concentrations during treatment with enalapril paralleled clinical and haemodynamic improvement, and probably reflected relief from renal hypoxia.

Adult↗
PubMed1989

Radiolabelling of human platelets with 99mTc-HMPAO.

The optimum conditions for labelling platelets with lipophilic 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO) were evaluated. An aseptic closed system was used throughout the procedure in patient studies. 48 ml blood were withdrawn into 12 ml ACD using sterile 60 ml plastic syringes. After mixing, the blood was transferred to sterile 10 ml vacuum tubes and platelets were isolated according to standard centrifugation procedures. The labelling efficiency was not dependent upon incubation temperature (22 degrees C, 37 degrees C) but was greater in saline than in the presence of plasma. The labelling efficiency increased with time up to 60 min in saline. The elution of 99mTc from platelets was about 25% in plasma milieu in vitro but did not increase with time during 160 min. 5 patients with verified fresh deep vein thrombosis in the lower leg were imaged after injection of labelled autologous platelets. All 4 of the patients without anticoagulant therapy showed positive uptake of 99mTc-HMPAO-labelled platelets, but the 5th patient--under heparin therapy--was negative in scintigraphy. Our results are encouraging and 99mTc-HMPAO-labelled platelets offer a promising tool for evaluating various clinical situations.

Blood Platelets↗
PubMed1988

FMRFamide-like immunoreactive neurons of the nervus terminalis of teleosts innervate both retina and pineal organ.

The tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) was first isolated from molluscan ganglia. Subsequently, it has become clear that vertebrate brains also contain endogenous FMRFamide-like substances. In teleosts, the neurons of the nervus terminalis contain an FMRFamide-like substance, and provide a direct innervation to the retina (Proc. Natl. Acad. Sci. U.S.A., 81 [1984] 940-944). Here we report the presence of FMRFamide-immunoreactive axonal bundles in the pineal organ of Coho salmon and three-spined sticklebacks. The largest numbers of axons were observed proximal to the brain, in the pineal stalk, while the distal part of the pineal organ contained only few axons. No FMRFamide-like-immunoreactive (IR) cell bodies were observed in the pineal organ. In adult fish it was not possible to determine the origin of these axons, due to the large numbers of FMRFamide-like IR axons in the teleost brain. However, by following the development of FMRFamide-like IR neurons in the embryonic and larval stickleback brain, it was possible to conclude that, at least in newly hatched fish, FMRFamide-like IR axons that originate in the nucleus nervus terminalis reach the pineal organ. Thus, it seems there is a direct connection between a specialized part of the chemosensory system and both the retina and the pineal organ in teleost fish.

Aging↗