Health and medication literacy and the desire to participate in pharmacotherapy decision making - comparison of two countries.

BACKGROUND: Health and medication literacy may be important factors in the outcomes of medical treatment. Similarly, shared decision making or lack of it may influence patient's behavior and adherence to medications. OBJECTIVES: To describe health and medication literacy as well as factors associated with poor medication literacy in two different populations and secondly, to describe desire to participate in decisions concerning medications; and to assess the role of poor medication literacy in decision making. METHODS: A general population based survey in Finland (n = 8003) and in Malta (n = 2000). Health and medication literacy and the desire to participate in decision making was each measured with three statements based on the literature. Medication literacy was operationalized as understanding the instructions on package insert and ability to follow instructions on pharmacy label. RESULTS: Fifteen percent of the Finnish respondents and 16% of Maltese reported always or often having problems understanding package inserts, i.e., poor medication literacy. Males (p = 0.004) and respondents in the age group 65-79 years (p < 0.001) were more prone to report such poor medication literacy. Respondents in Finland (59%) and Malta (65%) reported wanting to discuss different treatment options with the doctor. The respective percentages (42% Finland, 57% Malta) were lower for discussing about the choice of medicine and for deciding about the medicine (36% and 43%, respectively). The desire to participate in deciding about the medicines was higher among females (p < 0.001) and Maltese respondents (p < 0.001). Also those with poor medication literacy more often (p < 0.001) expressed a desire to participate in deciding in the choice of medicine. CONCLUSIONS: Medication literacy was rather low, while desire to participate in pharmacotherapy decision making was high, especially in Malta. Overall, women tended to be more willing to participate in decision making. The desire to participate in decisions was higher among persons with low medication literacy.

Internet as a source of medicines information (MI) among frequent internet users.

BACKGROUND: The internet is widely and increasingly used to search for health information. Previous studies have focused mainly on health information on the internet and not specifically on medicines information (MI). OBJECTIVES: The aim of this study was to explore the internet as a source of MI compared to other sources of MI; to identify those who use the internet as a source of MI; and to describe patterns of use of the internet as a source of MI. METHODS: A cross-sectional design employed a web-based questionnaire posted by patients' and other organizations as well as pharmacies on their websites during six weeks in the beginning of 2014. Logistic regression analysis was used to assess associations of background variables to the use of different MI sources. RESULTS: The most frequently used MI sources among respondents (n = 2489) were package leaflets (90%), pharmacists (83%), physicians (72%), and the internet (68%). According to a multivariate analysis, internet use for MI was associated with female gender, age <65 years, higher education, daily use of the internet, and continuous use of vitamins or herbals. MI was most commonly searched from a Finnish health portal (56%) and websites of pharmacies (41%). Of the respondents, nearly half (43%) used search engines to find information from the internet. The names of the medicinal product, symptom or disease were the most commonly used search terms. CONCLUSIONS: Well-educated, young women tend to search MI on the internet. Health care professionals should discuss reliable MI websites and tools that can help patients evaluate the reliability of information.

Hypoxia exposure and B-type natriuretic peptide release from Langendorff heart of rats.

AIM: We studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B-type natriuretic peptide (BNP) from Langendorff heart. METHODS: Rat hearts were isolated and perfused with a physiological Krebs-Henseleit solution at a constant hydrostatic pressure in Langendorff set-up. The basal O2 level of perfusate (24.4 ± 0.04 mg L-1 ) was gradually lowered to 3.0 ± 0.01 mg L-1 over 20 min using N2 gas (n = 7). BNP and O2 level were measured from coronary flow. During control perfusions (n = 5), the O2 concentration was kept at 26.6 ± 0.3 mg L-1 . RESULTS: A low oxygen concentration in the perfusate was associated with a significant increase in BNP release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration in the perfusate reached 9.1 ± 0.02 mg L-1 and continued to fall in lower oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but inverse correlation between BNP and oxygen in the coronary flow (R2  = 0.27, P < 0.001). CONCLUSION: In the spontaneously beating Langendorff rat heart, a decreasing concentration of oxygen in the ingoing perfusion increased the secretion of BNP. The effect of oxygen was independent of mechanical stretch of the heart as it occurred even when the heart rate decreased but the pressure conditions remained constant. The difference in the oxygen capacitance of blood and Krebs-Henseleit solution appears to be a major factor affecting secretion of BNP, which is correlated with the oxygen tension of myocardial cells and affected both by the oxygen concentration and capacitance of solution perfusing the heart and by the coronary flow.

Incorporating patient perspectives in health technology assessments and clinical practice guidelines.

BACKGROUND: Ensuring patient involvement in health technology assessments (HTAs) and clinical practice guidelines (CPGs) is important. However, the goals and methods of such involvement are not always clear. OBJECTIVES: The aim of this study was to 1) discover ways to involve patients in HTA and CPG processes, 2) describe challenges, and 3) find ways of informing patients about HTAs and CPGs in Finland. METHODS: As part of a one-day seminar targeted at representatives of patient organizations (POs), 3, 1-h focus group discussions were held (n = 20, with 14 PO representatives). PO representatives included real patients and health care professionals working in the organizations. The discussions were tape-recorded, transcribed, and thematically analyzed. RESULTS: Focus group participants highlighted the importance of gathering patient views from a group of patients, rather than individuals. Surveys through POs were the most frequently mentioned means of gathering patients' views. PO representatives reported interest in cooperating in HTA and CPG processes. The most often mentioned challenges were finding appropriate representatives for the target group and conveying information about HTAs and CPGs to patients. Multichannel communication was seen as essential. Furthermore the information should be readable, comprehensible, tailored, reliable, reusable, complementary, and timely. CONCLUSIONS: Possible strategies to involve patients in HTA and CPG processes were incorporating patient representatives in the CPG and HTA groups, offering timely possibility to participate, and ensuring reporting with clear and unambiguous language. The main identified challenge was finding appropriate representatives of the target group. The role of POs was seen as important particularly when informing the patients.

Facing warm temperatures during migration: cardiac mRNA responses of two adult Oncorhynchus nerka populations to warming and swimming challenges.

The main findings of the current study were that exposing adult sockeye salmon Onchorhynchus nerka to a warm temperature that they regularly encounter during their river migration induced a heat shock response at an mRNA level, and this response was exacerbated with forced swimming. Similar to the heat shock response, increased immune defence-related responses were also observed after warm temperature treatment and with a swimming challenge in two different populations (Chilko and Nechako), but with some important differences. Microarray analyses revealed that 347 genes were differentially expressed between the cold (12-13° C) and warm (18-19° C) treated fish, with stress response (GO:0006950) and response to fungus (GO:0009620) elevated with warm treatment, while expression for genes involved in oxidative phosphorylation (GO:0006119) and electron transport chain (GO:0022900) elevated for cold-treated fish. Analysis of single genes with real-time quantitative PCR revealed that temperature had the most significant effect on mRNA expression levels, with swimming and population having secondary influences. Warm temperature treatment for the Chilko population induced expression of heat shock protein (hsp) 90α, hsp90ß and hsp30 as well as interferon-inducible protein. The Nechako population, which is known to have a narrower thermal tolerance window than the Chilko population, showed even more pronounced stress responses to the warm treatment and there was significant interaction between population and temperature treatment for hsp90ß expression. Moreover, significant interactions were noted between temperature treatment and swimming challenge for hsp90α and hsp30, and while swimming challenge alone increased expression of these hsps, the expression levels were significantly elevated in warm-treated fish swum to exhaustion. In conclusion, it seems that adult O. nerka currently encounter conditions that induce several cellular defence mechanisms during their once-in-the-lifetime migration. As river temperatures continue to increase, it remains to be seen whether or not these cellular defences provide sufficient protection for all O. nerka populations.

Upper thermal tolerance of closely related Danio species.

The main finding of this study was that measuring maximum heart rate during incremental warming was an effective tool to estimate upper thermal limits in three small cyprinid Danio species, which differed significantly. Arrhenius breakpoint temperature for maximum heart rate, purportedly an index of optimum temperature, was 21·2 ± 0·4, 20·1 ± 0·4 and 18·9 ± 0·8° C (mean ± s.e.) for zebrafish Danio rerio, pearl danio Danio albolineatus and glowlight danio Danio choprae, respectively. The temperature where cardiac arrhythmias were first induced during warming (T(arr)) was 36·6 ± 0·7, 36·9 ± 0·8 and 33·2 ± 0·8° C (mean ± s.e.) and critical thermal maximum (T(Cm)) was 39·9 ± 0·1, 38·9 ± 0·1 and 37·2 ± 0·1° C (mean ± s.e.) for D. rerio, D. albolineatus and D. choprae, respectively. The finding that T(arr) was consistently 3-4° C lower than T(Cm) suggests that collapse of the cardiac life support system may be a critical trigger for upper temperature tolerance. The upper thermal limits established here, which correlate well with a broad natural environmental temperature range for D. rerio and a narrow one for D. choprae, suggest that upper thermal tolerance may be a genetic trait even among closely related species acclimated to common temperatures.

Medication use in pregnancy: a cross-sectional, multinational web-based study.

OBJECTIVES: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. DESIGN: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. SETTING: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. PARTICIPANTS: Pregnant women and new mothers with children less than 1 year of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. RESULTS: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. CONCLUSIONS: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.

Responses to temperature and hypoxia as interacting stressors in fish: implications for adaptation to environmental change.

Anthropogenic environmental change is exposing animals to changes in a complex array of interacting stressors and is already having important effects on the distribution and abundance of species. However, despite extensive examination of the effects of stressors in isolation, knowledge of the effects of stressors in combination is limited. This lack of information makes predicting the responses of organisms to anthropogenic environmental change challenging. Here, we focus on the effects of temperature and hypoxia as interacting stressors in fishes. A review of the available evidence suggests that temperature and hypoxia act synergistically such that small shifts in one stressor could result in large effects on organismal performance when a fish is exposed to the 2 stressors in combination. Although these stressors pose substantial challenges for fish, there also is substantial intraspecific variation in tolerance to these stressors that could act as the raw material for the evolution of improved tolerance. However, the potential for adaptive change is, in part, dependent on the nature of the correlations among traits associated with tolerance. For example, negative genetic correlations (or trade-offs) between tolerances to temperature and hypoxia could limit the potential for adaptation to the combined stressors, while positive genetic correlations might be of benefit. The limited data currently available suggest that tolerances to hypoxia and to high-temperature may be positively correlated in some species of fish, suggesting the possibility for adaptive evolution in these traits in response to anthropogenic environmental change.

Parental reporting of adverse drug events and other drug-related problems in children in Finland.

PURPOSE: Drug-related problems (DRPs) are common in paediatric pharmacotherapy, but few studies describe them from the parents' perspective. In the present survey, we have investigated the lifetime prevalence and type of DRPs in children in Finland. METHODS: This was a population-based survey of a random sample of 6,000 children below 12 years of age in 2007. A questionnaire was sent to their parents. The final response rate was 67% with a study population of 4,032. The main outcome measure was the lifetime prevalence and type of DRPs. RESULTS: The lifetime prevalence of DRPs was 21% (95% CI 20-22). The most common (82%) of the 1,346 reported DRPs were adverse drug events (ADEs). The prevalence of ADEs was 17% (95% CI 16-19), that of other DRPs 5.2% (95% CI 4.5-5.9). The prevalence of serious ADEs was 0.4% and that of unexpected ADEs was 0.8%. The most common system involved in the ADEs was the gastrointestinal tract, comprising 34% of the 1,106 ADEs. The most common of the 240 other DRPs were problems with the administration and dosing of medicine (86%). Overall, 64% of DRPs were related to anti-infectives. CONCLUSIONS: One fifth of the Finnish children below 12 years of age had experienced DRPs. Appropriate counselling, including possible adverse drug reactions and dosing directions, is important for parents and children at both the prescribing and dispensing of medicines for paediatric patients. Reporting of any suspected serious or unexpected ADEs is an essential part of efficient pharmacovigilance in paediatrics.

Using maximum heart rate as a rapid screening tool to determine optimum temperature for aerobic scope in Pacific salmon Oncorhynchus spp.

The mean ±s.e. optimum temperature (T(opt)) for aerobic scope in juvenile coho salmon Oncorhynchus kisutch was determined to be 17·0 ± 0·7° C. The repeated measures protocol took 3 weeks to complete the T(opt) determination using 12 fish tested at five temperatures separated by 2° C increments. This experiment also demonstrated that the T(opt) was associated with maximum heart rate (f(H)) failing to maintain a Q(10) -related increase with temperature. When maximum f(H) was produced in anaesthetized fish with pharmacological stimulation and f(H) measured from electrocardiogram recordings during acute warming, the Arrhenius break temperature (ABT) for Q(10) discontinuities in maximum f(H) (mean ±s.e. = 17·1 ± 0·5° C for 15 ppm clove oil and 16·5 ± 0·2° C for 50 ppm MS-222) was statistically indistinguishable from the T(opt) measured using aerobic scope. Such a determination took only 3 days rather than 3 weeks. Therefore, it is proposed that determining ABT for discontinuities in maximum f(H) in anaesthetized fish presents itself as a valuable, high-throughput screening tool to assess T(opt) in fishes, a metric that has become recognized as being extremely valuable in fish biology and fisheries management.

Effects of training on functional variables of muscles in reared Atlantic salmon Salmo salar smolts: connection to downstream migration pattern.

The relative amount of muscle contraction regulating dihydropyridine and ryanodine receptors in the swimming muscles of trained reared Atlantic salmon Salmo salar smolts was compared with those of untrained and wild smolts. After an optimized 2 week training period, i.e. swimming with a velocity of 1·5 body lengths per second for 6 h per day, the level of both receptors was significantly higher in the muscles of trained S. salar than in the untrained ones before they were released into the natural environment. This difference persisted after downstream migration in the river. The highest level of receptors was observed in wild S. salar. Swimming performance was also higher in trained fish compared to untrained ones. Furthermore, swimming performance was positively associated with the level of receptors in both red and white muscle types. Downstream migration after release into the wild was significantly slower in trained smolts than in untrained fish. This indicates that trained smolts were most probably swimming harder against the current in the river than untrained smolts. The possible advantages for a slower migration in the river are discussed. This study shows that the prerequisites for effective contraction of the swimming muscles are better met in trained S. salar compared to untrained fish, and the muscles of trained smolts more closely resemble those of wild smolts. The results also imply that the capacity of untrained, reared smolts to swim against the current is not equal to that of their trained or wild counterparts which affects the downstream migration pattern of S. salar smolts.

Embryo production from superovulated Holstein-Friesian dairy heifers and cows after insemination with frozen-thawed sex-sorted X spermatozoa or unsorted semen.

The aim of this study was to evaluate embryo production in superovulated Holstein-Friesian dairy heifers and cows inseminated with either X-sorted spermatozoa (2 million/dose) or unsorted semen (15 million/dose). Experiment 1 at the research farm involved eight heifers, six cows and semen of one Holstein bull. All transferable embryos were diagnosed for sex. Experiment 2 included embryo collections on commercial dairy farms: X-sorted spermatozoa from three Holstein bulls were used for 59 collections on 28 farms and unsorted semen from 32 Holstein bulls were used for 179 collections on 79 farms. Superovulations were induced by eight declining doses of FSH (total of 12 ml for heifers and 19 ml for cows) starting on days 8-12 of the estrus cycle. Inseminations began 12h after the onset of estrus and were performed two to four times at 9-15 h intervals. Low-dose X-sorted inseminates were deposited into uterine horns and unsorted semen was placed into the uterine body. In Experiment 1, on average 70.3 and 75.0% of embryos recovered from heifers, and 48.4 and 100% of embryos recovered from cows were of transferable quality in X-sorted and unsorted groups, respectively. The proportion of transferable female embryos produced approximately doubled when insemination was with X-sorted spermatozoa compared to insemination with unsorted semen (heifers 96.4% versus 41.1%; cows 81.1% versus 39.8%). In Experiment 2, estimated 53.9 and 65.5% of embryos recovered from heifers, and 21.1 and 64.5% of embryos recovered from cows were of transferable quality in X-sorted and unsorted groups, respectively. Proportions of unfertilized oocytes were 21.1 and 10.6% for heifers and 56.0 and 14.4% for cows in X-sorted and unsorted groups, respectively. Consequently, cows inseminated with X-sorted spermatozoa produced significantly smaller proportions of transferable embryos (p<0.005) and significantly larger proportions of unfertilized oocytes (p<0.001) than those inseminated with unsorted semen. Proportions of quality 1 or degenerated embryos were similar for the two treatments in both heifers and cows. Within treatments, bulls did not significantly affect the proportions of transferable, unfertilized or degenerated oocytes/embryos. It was concluded that using low-dose X-sorted spermatozoa rather than normal-dose unsorted semen for the insemination of superovulated embryo donors can improve the proportion of transferable female embryos produced but this potential may not be achieved in commercial practice, particularly in cows, because of reduced fertilization rates when using low doses of X-sorted spermatozoa.

Ultrastructural differences and histochemical characteristics in swimming muscles between wild and reared Atlantic salmon.

AIM: The swimming capacity of wild and reared fish differs. Whether the differences are associated with metabolic, contractile or structural variation in swimming musculature is unknown. In the present study, some aspects of contractile machinery in swimming muscles of wild and reared salmon are compared. METHODS: Several morphological parameters and key enzyme activities were measured using electron microscopy and histochemical methods. RESULTS: The density and size of the mitochondria was significantly higher in the muscle samples from wild fish when compared with the reared ones. Similar variability was also seen in the density of triads. Conversely, the size and density of lipid droplets was significantly lower in the red muscle of wild vs. reared salmon. The densities of two excitation contraction coupling components, dihydropyridine and ryanodine receptor, were considerably higher in swimming muscles of wild salmon than in reared fish. A similar difference was observed in the activities of aerobic enzymes. Moreover, oxygen consumption followed the same pattern, being significantly higher in the samples of wild salmon. Phosphorylase activity was, on the other hand, significantly lower in the muscles of wild fish. CONCLUSIONS: There are significant differences in morphology, Ca(2+)-regulating capacity and enzyme activities in swimming muscles between wild and reared salmon. These results provide evidence that the prerequisites for efficient contraction of the swimming muscles are better met in wild than in reared salmon. Importantly, the results also suggest that the observed variation is a major contributing factor to the difference in the swimming capacity between wild and hatchery-reared salmon.

Testosterone and Ca2+ regulation in skeletal muscle.

The aim of this study was to examine the effect of testosterone treatment on the expression of dihydropyridine and ryanodine receptors in skeletal muscle of mouse. Furthermore, the effects of training, a method also known to elevate the plasma testosterone level, were studied and compared to the effects of pure testosterone administration. Male mice were either administered with testosterone or trained with treadmill. After 6 weeks, hindlimb muscles were excised and the expression of receptors was measured by Western blotting. Furthermore, the alterations in myosin heavy chain phenotypes were studied. In general, both training and testosterone administration induced changes in the expression of both receptors and in myosin heavy chain composition. In testosterone treated mice the expression of dihydropyridine receptor in extensor digitorum longus was higher compared to the control ones (38.9 %, p = 0.026). In soleus the expression was quite the contrary (- 27.3 %, p = 0.044), as was the case with ryanodine receptor (- 51.4 %, p = 0.012). The amount of ryanodine receptors was higher in rectus femoris (144.0 %, p = 0.044) and plantaris (48.1 %, p = 0.037) in testosterone treated mice. In trained mice, the expression of ryanodine receptor was significantly higher in gastrocnemius (27.6 %, p = 0.018), soleus (57.2 %, p = 0.025), plantaris (28.5 %, p = 0.009) and extensor digitorum longus (94.8 %, p = 0.009) than in the control ones. No differences were observed in the dihydropyridine receptor level. To conclude, training has a more important role in skeletal muscle adaptation compared to increased plasma testosterone level. However, in postural muscles both treatments have comparable effects.

Effects of low-intensity training on dihydropyridine and ryanodine receptor content in skeletal muscle of mouse

To evaluate low-intensity exercise training induced changes in the expression of dihydropyridine (DHP) and ryanodine (Ry) receptors both mRNA and protein levels were determined by quantitative RT-PCR and immunoblot analysis from gastrocnemius (GAS) and rectus femoris (RF) muscles of mice subjected to a 15-week aerobic exercise program. The level of muscular work was assayed by changes in myosin heavy chain (MHC) content, myoglobin (Mb) expression and muscle size. The mRNA expression and optical density of DHP receptor increased significantly in GAS by 66.8 and 39.5%, respectively. The expression of Ry receptor, on the other hand, was not up-regulated. In RF, there was a significant increase of 38.4% in the mRNA expression of DHP receptor, although the protein level remained the same. No changes in Ry receptor expression was observed. The training resulted in a 1.58% increase in the amount of MHC IIa and a 2.34% decrease in that of IIb and IId in GAS. A significant 8.3% increase in the Mb content was observed. In RF, no significant changes in MHC or in Mb content were noted. Our results show that an evident increase in the mRNA and protein expression of DHP receptor was induced in GAS even by a relatively low-intensity exercise. Surprisingly, contrast to DHP receptor expression, no changes in Ry receptor mRNA, or protein levels were found, indicating more abundant demand for DHP receptor after increased muscle activity (AU)

Para evaluar los cambios inducidos en la expresión de los receptores de dihidropiridina (DHPR) y rianodina (RyR) por el entrenamiento con ejercicio de baja intensidad, se determinan los niveles de mRNA y de proteína mediante el análisis de RT-PCR cuantitativa e inmunoblot de los músculos gastrocnemius (GAS) y rectus femoris (RF) de ratón sometido a un programa de ejercicio aeróbico durante 15 semanas. El nivel de trabajo muscular fue determinado por los cambios en contenido de cadena pesada de miosina (MHC), expresión de mioglobina (Mb) y tamaño del músculo. La cantidad de mRNA y de proteína de DHPR aumentó significativamente en un 66,8 y 39,5% respectivamente. La expresión de RyR, por otro lado, no se vio incrementada. En RF hubo un aumento significativo del 22,7% en la expresión del mRNA de DHPR, aunque los niveles de proteína permanecieron inalterados. Tampoco se observaron cambios en la expresión de RyR en RF. El entrenamiento dio lugar a un aumento del 1,58% en la cantidad de MHC IIa y disminución del 2,34% en MHC IIb y IId en GAS, con incremento significativo del 8,3% en el contenido de Mb. En RF no se detectaron cambios significativos en el contenido en MHC ni en Mb. Nuestros resultados muestran que se induce un evidente aumento en el nivel de RNAm y de proteína DHPR en GAS mediante un ejercicio de relativamente baja intensidad. Sorprendentemente, en contraste con la expresión de DHPR, no se encontraron cambios en los niveles de mRNA ni de proteína de RyR, indicando mayor demanda de DHPR al incrementar la actividad muscular (AU)

Effects of low-intensity training on dihydropyridine and ryanodine receptor content in skeletal muscle of mouse.

To evaluate low-intensity exercise training induced changes in the expression of dihydropyridine (DHP) and ryanodine (Ry) receptors both mRNA and protein levels were determined by quantitative RT-PCR and immunoblot analysis from gastrocnemius (GAS) and rectus femoris (RF) muscles of mice subjected to a 15-week aerobic exercise program. The level of muscular work was assayed by changes in myosin heavy chain (MHC) content, myoglobin (Mb) expression and muscle size. The mRNA expression and optical density of DHP receptor increased significantly in GAS by 66.8 and 39.5%, respectively. The expression of Ry receptor, on the other hand, was not up-regulated. In RF, there was a significant increase of 38.4% in the mRNA expression of DHP receptor, although the protein level remained the same. No changes in Ry receptor expression was observed. The training resulted in a 1.58% increase in the amount of MHC IIa and a 2.34% decrease in that of IIb and IId in GAS. A significant 8.3% increase in the Mb content was observed. In RF, no significant changes in MHC or in Mb content were noted. Our results show that an evident increase in the mRNA and protein expression of DHP receptor was induced in GAS even by a relatively low-intensity exercise. Surprisingly, contrast to DHP receptor expression, no changes in Ry receptor mRNA, or protein levels were found, indicating more abundant demand for DHP receptor after increased muscle activity.

Measurement of free beam neutron spectra at eight BNCT facilities worldwide.

Eight epithermal neutron beams, constructed for clinical or preclinical studies of NCT, have been dosimetrically characterized by in-air measurements with a set of activation foils for the determination of the neutron energy spectra in free beam. Measurements have been made on the already closed epithermal BNCT facility at the BMRR of the Brookhaven National Laboratory, on the HFR at JRC in Petten, The Netherlands, on the epithermal mode beam at KURRI, Japan, on the fission converter beam at MIT, USA, on the epithermal beam of the RA-6 facility in Bariloche, Argentina, on the epithermal beam at WSU, USA, on the mixed mode beam at JRR-4 at JAERI, Japan, as well as on the epithermal beam at FiR 1 at VTT, Espoo, Finland.

Immediate effects of docetaxel alone or in combination with epirubicin on cardiac function in advanced breast cancer.

The immediate effects on cardiac function of 3-weekly docetaxel and combined docetaxel-epirubicin were evaluated during treatment of metastatic breast cancer using assessment of heart rate variability (HVR) and left ventricular ejection fraction (LVEF) measured by echocardiography. Twenty-four breast cancer patients were treated with docetaxel alone (starting dose 100 mg/m2) and 34 with a combination of docetaxel and epirubicin (starting dose for both drugs 75 mg/m2) administered 3-weekly. Single docetaxel caused no significant changes in HVR or cardiac function, whereas during combined treatment statistically significant changes were observed in mean RR intervals and in the number of supraventricular extrasystoles. Clinically the observed changes were insignificant. In conclusion, in 3-weekly administration the combined use of docetaxel and epirubicin was more likely than single docetaxel to cause changes in cardiac function.

Mycotoxins, fungus and 'electrohypersensitivity'.

'Electrohypersensitivity' is often explained as a psychological syndrome. Our modern environment contains a lot of different substances and some of them are toxic. Mycotoxins are types of toxins that are biologically very active and that affect living organisms. Mycotoxins and fungi capable of producing toxins have been detected in ventilation systems, water damage and in foodstuff. Many of those displaying symptoms caused by electromagnetic fields have fungus infections or have been living in fungus-contaminated environments for long periods. In animal studies mycotoxins have shown the same effects as those seen in the 'electrohypersensitivity' syndrome. Phototoxic reactions are well known in veterinary medicine and in medical science, so the question is whether the 'electrohypersensitivity' syndrome is caused by 'phototoxic' reactions?

The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers.

Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D2 receptor density in vivo in human striatum. Low D2 receptor binding in vivo has been found to associate with alcohol/substance dependence. It has been suggested that the A1 allele of human D2 receptor gene might be associated to a specific type of alcoholism and possibly to a reduced D2 receptor density in vitro. We have determined D2 dopamine receptor-binding density (Bmax), affinity (Kd) and availability (Bmax/Kd) in 54 healthy Finnish volunteers using PET and [11C]raclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D2 receptor characteristics in vivo. A statistically significant reduction in D2 receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent Kd between the two groups. In conclusion, the association between the A1 allele and low D2 receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.