Publications by authors named "Maria Lahtinen"

9 Publications

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Excess protein enabled dog domestication during severe Ice Age winters.

Sci Rep 2021 01 7;11(1). Epub 2021 Jan 7.

Faculty of Medicine, University of Helsinki, PO Box 63, 00014, Helsinki, Finland.

Dogs (Canis familiaris) are the first animals to be domesticated by humans and the only ones domesticated by mobile hunter-gatherers. Wolves and humans were both persistent, pack hunters of large prey. They were species competing over resources in partially overlapping ecological niches and capable of killing each other. How could humans possibly have domesticated a competitive species? Here we present a new hypothesis based on food/resource partitioning between humans and incipient domesticated wolves/dogs. Humans are not fully adapted to a carnivorous diet; human consumption of meat is limited by the liver's capacity to metabolize protein. Contrary to humans, wolves can thrive on lean meat for months. We present here data showing that all the Pleistocene archeological sites with dog or incipient dog remains are from areas that were analogous to subarctic and arctic environments. Our calculations show that during harsh winters, when game is lean and devoid of fat, Late Pleistocene hunters-gatherers in Eurasia would have a surplus of animal derived protein that could have been shared with incipient dogs. Our partitioning theory explains how competition may have been ameliorated during the initial phase of dog domestication. Following this initial period, incipient dogs would have become docile, being utilized in a multitude of ways such as hunting companions, beasts of burden and guards as well as going through many similar evolutionary changes as humans.
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http://dx.doi.org/10.1038/s41598-020-78214-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790815PMC
January 2021

Buried in water, burdened by nature-Resilience carried the Iron Age people through Fimbulvinter.

PLoS One 2020 21;15(4):e0231787. Epub 2020 Apr 21.

Department of Cultures, Archaeology, University of Helsinki, Helsinki, Finland.

Levänluhta is a unique archaeological site with the remains of nearly a hundred Iron Age individuals found from a water burial in Ostrobothnia, Finland. The strongest climatic downturn of the Common Era, resembling the great Fimbulvinter in Norse mythology, hit these people during the 6th century AD. This study establishes chronological, dietary, and livelihood synthesis on this population based on stable carbon and nitrogen isotopic and radiocarbon analyses on human remains, supported by multidisciplinary evidence. Extraordinarily broad stable isotopic distribution is observed, indicating three subgroups with distinct dietary habits spanning four centuries. This emphasizes the versatile livelihoods practiced at this boundary of marine, freshwater, and terrestrial ecosystems. While the impact of the prolonged cold darkness of the 6th century was devastating for European communities relying on cultivation, the broad range of livelihoods provided resilience for the Levänluhta people to overcome the abrupt climatic decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231787PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173937PMC
July 2020

Mechanism-based population pharmacokinetic and pharmacodynamic modeling of intravenous and intranasal dexmedetomidine in healthy subjects.

Eur J Clin Pharmacol 2015 Oct 2;71(10):1197-207. Epub 2015 Aug 2.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, 404 Kapoor Hall, State University of New York at Buffalo, Buffalo, NY, 14214, USA.

Purpose: Dexmedetomidine is an α2-adrenoceptor agonist used for perioperative and intensive care sedation. This study develops mechanism-based population pharmacokinetic-pharmacodynamic models for the cardiovascular and central nervous system (CNS) effects of intravenously (IV) and intranasally (IN) administered dexmedetomidine in healthy subjects.

Method: Single doses of 84 μg of dexmedetomidine were given once IV and once IN to six healthy men. Plasma dexmedetomidine concentrations were measured for 10 h along with plasma concentrations of norepinephrine (NE) and epinephrine (E). Blood pressure, heart rate, and CNS drug effects (three visual analog scales and bispectral index) were monitored to assess the pharmacological effects of dexmedetomidine. PK-PD modeling was performed for recently published data (Eur J Clin Pharmacol 67: 825, 2011).

Results: Pharmacokinetic profiles for both IV and IN doses of dexmedetomidine were well fitted using a two-compartment PK model. Intranasal bioavailability was 82%. Dexmedetomidine inhibited the release of NE and E to induce their decline in blood. This decrease in NE was captured with an indirect response model. The concentrations of the mediator NE served via a biophase/transduction step and nonlinear pharmacologic functions to produce reductions in blood pressure and heart rate, while a direct effect model was used for the CNS effects.

Conclusion: The comprehensive panel of two biomarkers and seven response measures were well captured by the population PK/PD models. The subjects were more sensitive to the CNS (lower EC 50 values) than cardiovascular effects of dexmedetomidine.
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http://dx.doi.org/10.1007/s00228-015-1913-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167593PMC
October 2015

Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients.

Crit Care 2011 26;15(5):R257. Epub 2011 Oct 26.

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, PO Box 52, FI-20521 Turku, Finland.

Introduction: Only limited information exists on the pharmacokinetics of prolonged (> 24 hours) and high-dose dexmedetomidine infusions in critically ill patients. The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses. Additionally, we wanted to quantify for the first time in humans the concentrations of H-3, a practically inactive metabolite of dexmedetomidine.

Methods: Thirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score (SAPS) II score of 45 were included in the study. Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours. After the first 12 hours, the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 μg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale. Dexmedetomidine was continued as long as required to a maximum of 14 days. Plasma dexmedetomidine and H-3 metabolite concentrations were measured, and pharmacokinetic variables were calculated with standard noncompartmental methods. Safety and tolerability were assessed by adverse events, cardiovascular signs, and laboratory tests.

Results: The following geometric mean values (coefficient of variation) were calculated: length of infusion, 92 hours (117%); dexmedetomidine clearance, 39.7 L/h (41%); elimination half-life, 3.7 hours (38%); and volume of distribution during the elimination phase, 223 L (35%). Altogether, 116 steady-state concentrations were found in 12 subjects. The geometric mean value for clearance at steady state was 53.1 L/h (55%). A statistically significant linear relation (r2 = 0.95; P < 0.001) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine. The elimination half-life of H-3 was 9.1 hours (37%). The ratio of AUC0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 (105%), ranging from 0.29 to 4.4. The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion.

Conclusions: The results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 μg/kg/h. Despite the high dose and prolonged infusions, safety findings were as expected for dexmedetomidine and the patient population.

Trial Registration: ClinicalTrials.gov: NCT00747721.
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http://dx.doi.org/10.1186/cc10518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334808PMC
August 2012

Bioavailability of dexmedetomidine after intranasal administration.

Eur J Clin Pharmacol 2011 Aug 12;67(8):825-31. Epub 2011 Feb 12.

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland.

Purpose: The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers.

Methods: Single doses of 84 μg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine.

Results: Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15-60) min and its absolute bioavailability was 65% (35-93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration.

Conclusions: Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.
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http://dx.doi.org/10.1007/s00228-011-1002-yDOI Listing
August 2011

Metabolic modifications of birch leaf phenolics by an herbivorous insect: detoxification of flavonoid aglycones via glycosylation.

Z Naturforsch C J Biosci 2004 May-Jun;59(5-6):437-44

Laboratory of Environmental Chemistry, Department of Chemistry, University of Turku, Turku, Finland.

The metabolic modifications of birch (Betula pubescens Ehrh.) leaf phenolics in the digestive tract of its major defoliator, larvae of the autumnal moth Epirrita autumnata, were studied. The main phenolic acids of birch, i.e. chlorogenic and p-coumaroylquinic acids, were isomerised in the alkaline digestive tract. Moreover, only 16 to 92% of the ingested amounts of chlorogenic acid were found in the faeces of individual larvae; the missing portion is possibly being used in the formation of reactive o-quinones. Water-soluble flavonoid glycosides were mostly excreted unaltered. In contrast, lipophilic flavonoid aglycones were not excreted as such, but as glycosides after being detoxified by E. autumnata via glycosylation. When the larvae were fed with leaf-painted acacetin and kaempferide, i.e. two naturally occurring birch leaf flavonoid aglycones, acacetin-7-O-glucoside and kaempferide-3-O-glucoside appeared in larval faeces as major metabolites. However, the efficiency of aglycone glycosylation varied-, ranging from 17 to 33%, depending on the aglycone and its dietary level. There was also large variation in the efficiency of glycosylation--from 2 to 57%--among individual larvae. These results demonstrate a compound-specific metabolism of phenolic compounds, leading to different phenolic profiles in the insect gut compared to its leaf diet.
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http://dx.doi.org/10.1515/znc-2004-5-627DOI Listing
January 2009

HPLC analysis of leaf surface flavonoids for the preliminary classification of birch species.

Phytochem Anal 2006 May-Jun;17(3):197-203

Laboratory of Organic Chemistry and Chemical Biology. Department of Chemistry, University of Turku, FI-20014 Turku, Finland.

Flavonoid aglycones found on the surfaces of birch (Betula spp.) leaves may constitute up to 10% of the dry weight of the leaf. A facile extraction and HPLC procedure has been developed that can be used for the preliminary classification of birch species according to the patterns of their leaf surface flavonoids. The procedure involves no complex sample preparation steps, and is able to provide HPLC chromatograms from fresh leaves in less than 30 min. If necessary, leaves do not even need to be removed from the tree. Since the genus Betula is taxonomically complex and separation of different birch species can be problematic, the developed method was applied to 15 Betula species and four sub-species of Betula pendula Seven of the studied species were classified as B. pubescens and eight as B. pendula-type birches. The remaining four species did not belong to either of these two classes on account of their unique pattern of external flavonoids. The difference between the leaf surface flavonoid composition of B. pubescens and B. pendula type birch species was unambiguously clear, and the developed method could reliably distinguish between the two species. Whilst leaf surface flavonoids can be valuable chemotaxonomic markers, they classify birch species differently from morphological markers. Birch species with diploid chromosome sets did not contain any of the flavanones that were present in the leaves of other species. The close relationship between the occurrence of some flavonoid aglycones and the ploidy level of Betula species suggests that these chemotaxonomic markers may be useful both in taxonomic and phylogenetic analyses.
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http://dx.doi.org/10.1002/pca.906DOI Listing
July 2006

Newly hatched neonate larvae can glycosylate: the fate of Betula pubescens bud flavonoids in first instar Epirrita autumnata.

J Chem Ecol 2006 Mar 30;32(3):537-46. Epub 2006 Mar 30.

Laboratory of Organic Chemistry and Chemical Biology, Department of Chemistry, University of Turku, Finland.

Betula pubescens bud flavonoid aglycones reportedly have negative effects on the performance of first instar Epirrita autumnata and, thus, may defend birch leaves from larval defoliation. We hypothesized that the detrimental effects of these lipophilic flavonoids on larvae are due to their high levels in birch buds and/or the inability of naïve neonates to glycosylate them, which we have shown to occur in fifth instars. To test the latter hypothesis, we investigated the biochemical transformation of bud flavonoids in first instar E. autumnata. We found that newly hatched larvae have the ability to glycosylate birch bud/leaf flavonoid aglycones into corresponding glycosides. Moreover, we suggest that glycosylation may depend upon the chemical character of the aglycone and is an important factor in the performance of first instars.
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http://dx.doi.org/10.1007/s10886-005-9015-6DOI Listing
March 2006

Defensive effect of surface flavonoid aglycones of Betula pubescens leaves against first instar Epirrita autumnata larvae.

J Chem Ecol 2004 Nov;30(11):2257-68

Laboratory of Environmental Chemistry, Department of Chemistry University of Turku, FI-20014 Turku, Finland.

The surface of birch leaves contains glandular trichomes that secrete exudates containing flavonoid aglycones. We investigated the biological activities of white birch (Betula pubescens) leaf surface exudates against larvae of the autumnal moth, Epirrita autumnata, a common insect pest of birch. We found that tree-specific mortality (up to 100%) of first instar larvae correlated strongly with the tree-specific contents of surface flavonoid aglycones (r(s) = 0.905) in emerging leaves. We also found that first instars clearly preferred birch buds from which surface exudates had been removed. In addition, the duration of the first instar was shortened by 29%, and the weights and relative growth rates of first instars improved by 8% and 52%, respectively, as a result of removal of the exudates from their leaf diet. The correlation of tree-specific foliar contents of flavonoid aglycones, especially 5-hydroxy-4',7-dimethoxyflavanone, with changes in larval performance, suggests that flavonoid aglycones are responsible for the changes observed in first instar larval performance. The results show that chemical characteristics of birch leaves are effective against neonate E. autumnata larvae. However, the removal of leaf surface exudates from fully expanded leaves did not affect the leaf acceptance for the voracious fifth instars. This is probably a result of reduction in contents of flavonoid aglycones compared to those of emerging leaves.
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http://dx.doi.org/10.1023/b:joec.0000048787.34388.ddDOI Listing
November 2004