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1.  Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5-dihydrothiazole in female mice 
The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development, was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life.
PMCID: PMC4528559  PMID: 26136453
male murine pheromone; mammary gland development; nursing behaviour; cross-generational impact; polysialyltransferase; cognitive function
2.  Potentially severe drug–drug interactions among older people and associations in assisted living facilities in Finland: a cross-sectional study 
This study aims to assess potentially severe class D drug–drug interactions (DDDIs) in residents 65 years or older in assisted living facilities with the use of a Swedish and Finnish drug–drug interaction database (SFINX).
A cross-sectional study of residents in assisted living facilities in Helsinki, Finland.
A total of 1327 residents were assessed in this study. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and DDDIs were coded according to the SFINX.
Main outcome measures
Prevalence of DDDIs, associated factors and 3-year mortality among residents.
Of the participants (mean age was 82.7 years, 78.3% were females), 5.9% (N = 78) are at risk for DDDIs, with a total of 86 interactions. Participants with DDDIs had been prescribed a higher number of drugs (10.8 (SD 3.8) vs. 7.9 (SD 3.7), p < 0.001). A larger proportion of residents with DDDIs suffered from rheumatoid arthritis or osteoarthritis than those not exposed to DDDIs (24.7% vs. 15.4%, p = 0.030). The most frequent DDDIs were related to the concomitant use of potassium with amiloride (N = 12) or spironolactone (N = 12). Carbamazepine (N = 13) and methotrexate (N = 9) treatments were also frequently linked to DDDIs. During the follow-up, no differences in mortality emerged between the participants exposed to DDDIs and the participants not exposed to DDDIs.
Of the residents in assisted living, 5.9% were exposed to DDDIs associated with the use of a higher number of drugs. Physicians should be trained to find safer alternatives to drugs associated with DDDIs.
Key Points
Potentially severe, class D drug–drug interactions (DDDIs) have been defined in the SFINX database as clinically relevant drug interactions that should be avoided. • Of the residents in assisted living, 5.9% were exposed to DDDIs that were associated with the use of a higher number of drugs. • The most frequent DDDIs were related to the concomitant use of potassium with amiloride or spironolactone. Carbamazepine and methotrexate were also linked to DDDIs. • No difference in mortality was observed between residents exposed to DDDIs and residents not exposed to DDDIs.
PMCID: PMC5036014  PMID: 27428445
Assisted living; drug–drug interactions; Finland; general practice; mortality
3.  Are single odorous components of a predator sufficient to elicit defensive behaviors in prey species? 
When exposed to the odor of a sympatric predator, prey animals typically display escape or defensive responses. These phenomena have been well-documented, especially in rodents, when exposed to the odor of a cat, ferret, or fox. As a result of these experiments new discussions center on the following questions: (1) is a single volatile compound such as a major or a minor mixture constituent in urine or feces, emitted by the predator sufficient to cause defensive reactions in a potential prey species or (2) is a whole array of odors required to elicit a response and (3) will the relative size or escapability of the prey as compared to the predator influence responsiveness. Most predator-prey studies on this topic have been performed in the laboratory or under semi-natural conditions. Field studies could help to find answers to these questions. Australian mammals are completely naïve toward the introduced placental carnivores. That offers ideal opportunities to analyze in the field the responses of potential prey species to unknown predator odors. During the last decades researchers have accumulated an enormous amount of data exploring the effects of eutherian predator odors on native marsupial mammals. In this review, we will give a survey about the development of olfactory research, chemical signals and their influence on the behavior and—in some cases—physiology of prey species. In addition, we report on the effects of predator odor experiments performed under natural conditions in Australia. When studying all these literature we learned that data gained under controlled laboratory conditions elucidate the role of individual odors on brain structures and ultimately on a comparatively narrow range behaviors. In contrast to single odors odor arrays mimic much more the situation prey animals are confronted to in nature. Therefore, a broad range of methodology—from chemistry to ecology including anatomy, physiology, and behavior—is needed to understand all the different (relevant) stimuli that govern and guide the interactions between a predator and its potential prey.
PMCID: PMC4518157  PMID: 26283903
predator odors; aging of odors; predator naive prey; odor avoidance; field studies in Australia
4.  Modulation of social behavior by the agouti pigmentation gene 
Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.
PMCID: PMC4117936  PMID: 25136298
social behavior; agouti; melanocortin receptors; preputial glands; volatile organic compounds (VOCs); sorptive stir bar extraction (SBSE)
5.  Stimulation of cell proliferation in the subventricular zone by synthetic murine pheromones 
Adult neurogenesis in female mice is known to be enhanced by exposure to soiled bedding from males, although the identity of the relevant chemosignals has remained unknown. Here we show that the previously recognized male murine pheromones, the farnesenes and 2-sec-butyl-4,5-dihydrothiazole (SBT), strongly increase cell proliferation in the subventricular zone (SVZ) of adult female mice, but not younger female mice. In addition, we found that a unique female murine pheromone, 2,5-dimethylpyrazine, facilitates similar changes in males. SBT stimulated cell proliferation in the SVZ of only adult females and not in young adult or pre- and post-puberty females. Our study suggests that pheromonal communication between males and females is enhancing reproductive success by controlling the estrous cycle and by promoting cell proliferation in a reciprocal manner.
PMCID: PMC3734356  PMID: 23964214
pheromones; enhanced cell proliferation; subventricular zone; male; female; mice
6.  Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial 
Trials  2012;13:85.
Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people’s drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents’ quality of life and use of health services.
Methods and design
During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months.
The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations.
To our knowledge, this is the first large-scale randomized trial exploring whether relatively light intervention, that is, staff training, will have an effect on reducing harmful drugs and improving QOL among institutionalized older people.
Trial registration
PMCID: PMC3541247  PMID: 22709731
Inappropriate drugs; Psychotropic drugs; Anticholinergic drugs; Drug-drug interactions; Polypharmacy; Assisted living; Serviced housing; Randomized controlled trial
7.  Songbird chemosignals: volatile compounds in preen gland secretions vary among individuals, sexes, and populations 
Behavioral Ecology  2010;21(3):608-614.
Chemical signaling has been documented in many animals, but its potential importance in avian species, particularly songbirds, has received far less attention. We tested whether volatile compounds in the preen oil of a songbird (Junco hyemalis) contain reliable information about individual identity, sex, or population of origin by repeated sampling from captive male and female juncos originating from 2 recently diverged junco populations in southern California. One of the populations recently colonized an urban environment; the other resides in a species-typical montane environment. The birds were field-caught as juveniles, housed under identical conditions, and fed the same diet for 10 months prior to sampling. We used capillary gas chromatography–mass spectrometry to quantify the relative abundance of 19 volatile compounds previously shown to vary seasonally in this species. We found individual repeatability as well as significant sex and population differences in volatile profiles. The persistence of population differences in a common environment suggests that preen oil chemistry likely has a genetic basis and may thus evolve rapidly in response to environmental change. These finding suggest that songbird preen oil odors have the potential to function as chemosignals associated with mate recognition or reproductive isolation.
PMCID: PMC2854530  PMID: 22475692
birds; chemical communication; Junco hyemalis; olfaction; pheromones
8.  Biochemical Individuality Reflected in Chromatographic, Electrophoretic and Mass-Spectrometric Profiles 
This review discusses the current trends in molecular profiling for the emerging systems biology applications. Historically, the methodological developments in separation science were coincident with the availability of new ionization techniques in mass spectrometry. Coupling miniaturized separation techniques with technologically-advanced MS instrumentation and the modern data processing capabilities are at the heart of current platforms for proteomics, glycomics and metabolomics. These are being featured here by the examples from quantitative proteomics, glycan mapping and metabolomic profiling of physiological fluids.
PMCID: PMC2603028  PMID: 18551752
systems biology; metabolomic profiling; quantitative proteomics; glycomic profiling; biodiversity; animal models; bioinformatics; stable isotope labeling; metabolic stable isotope labeling LC-MS; GC-MS
9.  Individual and gender fingerprints in human body odour 
Individuals are thought to have their own distinctive scent, analogous to a signature or fingerprint. To test this idea, we collected axillary sweat, urine and saliva from 197 adults from a village in the Austrian Alps, taking five sweat samples per subject over 10 weeks using a novel skin sampling device. We analysed samples using stir bar sorptive extraction in connection with thermal desorption gas chromatograph–mass spectrometry (GC–MS), and then we statistically analysed the chromatographic profiles using pattern recognition techniques. We found more volatile compounds in axillary sweat than in urine or saliva, and among these we found 373 peaks that were consistent over time (detected in four out of five samples per individual). Among these candidate compounds, we found individually distinct and reproducible GC–MS fingerprints, a reproducible difference between the sexes, and we identified the chemical structures of 44 individual and 12 gender-specific volatile compounds. These individual compounds provide candidates for major histocompatibility complex and other genetically determined odours. This is the first study on human axillary odour to sample a large number of subjects, and our findings are relevant to understanding the chemical nature of human odour, and efforts to design electronic sensors (e-nose) for biometric fingerprinting and disease diagnoses.
PMCID: PMC2359862  PMID: 17251141
individual odour; chemical communication; volatile biomarkers; metabolomics; chemometric pattern recognition

Results 1-9 (9)