Breeding performance of blue tits (Cyanistes caeruleus) and great tits (Parus major) in a heavy metal polluted area.

We compared heavy metal levels, calcium levels, breeding parameters and condition of nestling and adult Cyanistes caeruleus and Parus major along a heavy metal pollution gradient. Both species started laying earlier and showed inferior nestling growth and smaller fledging probability in the polluted areas, which are phenologically advanced in spring due to sparse forests. The major inter-specific difference in the responses was that the clutch size and hatching success were decreased in the polluted area in P. major, but not in C. caeruleus. Heavy metal profiles in nestling feces were relatively similar in the two species, though Ni and Pb levels were higher in C. caeruleus than in P. major. However, the latter species showed markedly higher fecal calcium concentrations. Lower calcium levels and higher levels of some heavy metals in C. caeruleus suggest that in Ca-deficient environments this species might be more susceptible to negative pollution effects than P. major.

Alkyl-substituted silica gel as a carrier in the controlled release of dexmedetomidine.

The effect of alkyl substitution of the silica xerogel matrix on the release rate of dexmedetomidine was evaluated. Silica sol was processed by either casting or spray drying. When the reaction precursor tetraethylorthosilicate (TEOS) was partially substituted with tri- or dialkoxysilane, the release of dexmedetomidine and degradation of the matrix were decreased compared with 100% TEOS-based gel. Increasing the number or length of the organic groups attached to silicon, modified the silica gel structure and reduced the release rate of dexmedetomidine from monoliths. The release of dexmedetomidine from alkyl-substituted silica gel microparticles, however, showed a burst in drug release. Subcutaneously administered silica xerogel matrices (manufactured by casting, containing 25 mol% dimethyldiethoxysilane at two different doses of dexmedetomidine) were studied in dogs. Sustained delivery of dexmedetomidine was obtained for at least 48 h.

In vitro release of heparin from silica xerogels.

Heparin, a powerful anticoagulant used for the prophylaxis of both surgical and medical thrombosis, was incorporated into a silica xerogel matrix during polycondensation of organic silicate. The influence of various chemical sol-gel parameters (the properties of reaction precursors, catalyst and final moisture content of the gel and heparin concentration) was studied. The release of heparin from the gel was according to zero order during the dissolution period and the release rate of heparin was proportional to the drug load in the concentration range between 6.8 and 13.6 wt%. It was found that the catalyst used for the preparation of the gel, the final moisture content and the chemical modification of silica xerogel network have an influence on the release rate of heparin. The released heparin from all the different xerogels studied retained about 90% of its biological activity.

In vitro release of dexmedetomidine from silica xerogel monoliths: effect of sol-gel synthesis parameters.

Dexmedetomidine, an alpha 2-agonist, was incorporated as a hydrochloride salt into silica xerogel in order to evaluate the effect of sol-gel synthesis parameters: pH of the sol, water/alkoxide molar ratio, drug concentration and size of the device on the drug release rate and degradation rate of the matrix. This study showed that diffusion controlled the release of dexmedetomidine from silica xerogel prepared between pH 1 and pH 5. The drug release was, however, slowest near the zero charge of silica xerogel (pH 2-3). The burst of dexmedetomidine, a lipophilic, but in the form of hydrochloride salt water-soluble drug, was increased from the matrix prepared either below or above the isoelectric point. It follows that the optimum pH for preparing a drug delivery device for dexmedetomidine, is near the zero charge of silica xerogel, where the degradation of the matrix was also slowest. In addition to processing pH, the release rate of drugs can be controlled by changing the water/alkoxide molar ratio of the sol.

Effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) on toremifene citrate release from copolymer/silica xerogel composites.

The purpose of this study was to develop a biodegradable polymeric carrier system for toremifene citrate based on epsilon-caprolactone/DL-lactide copolymers and silica xerogel. The effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) affecting the release rate of toremifene citrate from copolymer/silica xerogel composites was evaluated by in vitro dissolution study. Lower and higher molecular weight copolymers (LMW 60000 g/mol and HMW 300000 g/mol) were used in the devices. Drug release was compared from the (copolymer/drug) matrix device and the (copolymer/drug impregnated silica xerogel) composite device. Hydrolysis of the copolymer devices was evaluated by water absorption, weight loss and change of molecular weight by size exclusion measurements (SEC). Controlled release of toremifene citrate was obtained from both matrix and composite devices and the release rate was most affected by the initial molecular weight of the copolymer. Throughout the study better results were obtained with LMW devices, since drug release was steady for nearly 1 year and no changes in the release rate were observed. The drug release was diffusion controlled from both LMW matrix and composite devices. Incorporation of toremifene citrate into the silica xerogel was found to enhance the drug release rate. The copolymer matrices degraded by random hydrolytic chain scission and, unexpectedly, HMW P(CL/LA) degraded faster than LMW P(CL/LA). The release of toremifene citrate from HMW devices was not complete before the second stage of polymer degradation began.

In vitro evaluation of sol-gel processed spray dried silica gel microspheres as carrier in controlled drug delivery.

The objective of this study was to evaluate sol-gel-derived spray dried silica gel microspheres as carrier material for dexmedetomidine HCl and toremifene citrate. The drug was dissolved in sol-gel processed silica sol before spray drying with Büchi laboratory scale equipment. Microspheres with a low specific surface area were spherical by shape with a smooth surface without pores on the external surface. The particle size distribution was quite narrow. The in vitro release of toremifene citrate and dexmedetomidine HCl showed a dose-dependent burst followed by a slower release phase, that was proportional to the drug concentration in the concentration range between 3.9 and 15.4 wt.%. The release period for toremifene citrate was approximately 10 days and for dexmedetomidine HCl between 7 and 50 days depending on drug concentration. Spray drying is a promising way to produce spherical silica gel particles with a narrow particle size range for controlled delivery of toremifene citrate and dexmedetomidine HCl.

Silica xerogel carrier material for controlled release of toremifene citrate.

Sol-gel processed silica xerogel was used as a carrier material for toremifene citrate in order to develop an implantable controlled release formulation which could be localised to a desired site providing targeted and long-lasting disease control and resulting in a reduced amount of drug needed. Toremifene citrate, an anti-estrogenic compound, was incorporated into silica xerogel matrixes during polycondensation of organic silicate, tetraethyl ortho silicate (TEOS). The effects of drug amount, drying temperature and polyethylene glycol (PEG) on the release rate of toremifene citrate and degradation of the silica xerogel matrixes were investigated. Addition of PEG (M(w) 4600/10000) decreased the specific surface area of the matrix and lowered the release rate of the drug. Reducing the amount of drug in the matrix also decreased the release rate of toremifene citrate. However, drying temperature did not affect the release rate of silica or toremifene citrate. The release profiles of toremifene citrate were according to zero order kinetics, suggesting that drug release was controlled by erosion of the silica xerogel matrix. These results suggest that the toremifene citrate release rate can be controlled to some extent by adding (PEG) or by varying the amount of drug in the silica xerogel matrix.

Silica xerogel as an implantable carrier for controlled drug delivery--evaluation of drug distribution and tissue effects after implantation.

The purpose of the present study was to examine controlled delivery of toremifene citrate from subcutaneously implanted silica xerogel carrier and to evaluate silica xerogel related tissue effects after implantation. Toremifene citrate was incorporated into hydrolyzed silica sol in a room temperature process. Toremifene citrate treated silica xerogel implants were tested both in vitro and in vivo using healthy mice. Silica xerogel with tritium-labelled toremifene was implanted subcutaneously in mice for 42 d. To determine the amount of tritiated toremifene remaining in the silica discs at the implantation site, the discs were excised periodically and radioactivity measured. The amount of tritiated toremifene in the implant after 42 d was still about 16% and the amount of silica xerogel about 25%. In a histopathological study silica xerogel did not show any tissue irritation at the site of the implantation. A fibrotic capsule was formed around the implant. No silica xerogel related histological changes in liver, kidney, lymph nodes and uterus were observed during the implantation period. The silica xerogel discs showed a sustained release of toremifene citrate over 42 d. Histologically, toremifene-related changes in the uterus were also detectable at all studied time points. These findings suggest that silica xerogel is a promising carrier material for implantable controlled drug delivery system.

In vitro release behavior of toremifene citrate from sol-gel processed sintered silica xerogels.

Factors affecting the adsorption and desorption of toremifene citrate (TC) on sintered silica xerogels were investigated in vitro. TC was attached onto sol-gel processed sintered silica xerogel grains or disks by adsorption. The adsorption of TC on the surface of silica was pH dependent. The results support the conclusion that large pore size results in highest drug adsorption. Adsorption of TC was most effective in xerogels sintered at 700 degrees C and containing the largest pores and lowest specific surface area of the silica xerogels studied in the adsorption tests. The release of TC from the xerogel matrix was linear with respect to the square root of time. The release of TC from the grains was very rapid for the first 5 hr, followed by a slower release. All drug was released from the grains, and 60% to 80% was released from the disks in 24 hr. All drug-silica xerogel formulations showed sustained in vitro release profiles.

Sol-gel-processed sintered silica xerogel as a carrier in controlled drug delivery.

Sol-gel-processed sintered silica xerogel was studied as a controllable, dissolvable, implantable material. The erosion of the matrix and the release of the preadsorbed drug toremifene citrate was investigated both in vitro and in vivo using mice. In an in vitro dissolution study, 50 to 60% of the drug was released after 24 h, according to the square root of time kinetics, and the weight loss of the silica was 24 wt %. Silica xerogel with tritium-labeled toremifene was implanted subcutaneously in mice for 56 days. To determine the amount of tritiated drug remaining in the silica disks at the implantation site, the disks were excised periodically and the radioactivity measured. About 40% of the radioactivity was released during the first 4 days and all of it within 28 days. Radioactivity also was measured in the liver, lungs, kidneys, uterus, and blood. The radioactivity reached a maximum level after 4 days in the liver, kidneys, and lungs and slowly decreased until all of the drug had been released from the matrix after 28 days. After release of the drug (28 days) the amount of remaining silica xerogel implant was 45 wt %, and at the end of the study (56 days) it was 24 wt %. In the histopathological study, sintered silica xerogel did not show any tissue toxicity at the site of the implantation, in the liver, or in the kidneys. It was concluded that sintered silica xerogel is a biocompatible and controllably resorbable material and therefore is a promising matrix for use in the sustained delivery of drugs.

In vitro evaluation of biodegradable epsilon-caprolactone-co-D, L-lactide/silica xerogel composites containing toremifene citrate.

Poly(epsilon-caprolactone-co-D,L-lactide) polymers were blended with toremifene citrate or with toremifene citrate impregnated silica xerogel in order to develop a controlled release formulation. The copolymers were synthesized by bulk polymerization and characterized by nuclear magnetic resonance, size exclusion chromatography and differential scanning calorimetry analyses. The in vitro release of toremifene citrate, an antiestrogenic compound, and silica was carried out in simulated body fluid (pH 7.4) containing 0.5 wt% sodium dodecylsulphate at 34 degrees C. The in vitro release studies indicate that the release flux of toremifene citrate increases with increasing weight fraction of caprolactone in the copolymer. Silica xerogel had a minor enhancing effect on the release rate of toremifene citrate. Copolymers containing larger amounts of D,L-lactide (PLA-CL20 and PLA-CL40 copolymers) were not suitable matrices for the delivery of toremifene citrate in a controlled manner because of the burst effect. The fraction of toremifene citrate released from PLA-CL80 matrix increased with the increasing loading of toremifene citrate. The results of the study indicate that the in vitro release of toremifene citrate can be adjusted by varying the polymer composition and also the initial drug loading.

High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease.

High density lipoprotein (HDL) subfractions (2b, 2a, 3a, 3b, and 3c) separated by gradient gel electrophoresis (GGE) and defined by Gaussian summation analysis, and the compositions of HDL2 and HDL3, separated by preparative ultracentrifugation, were studied in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD): group 1 (DM+CAD+, n = 50); group 2 (DM-CAD+, n = 50); group 3 (DM+CAD-, n = 50); and group 4 (DM-CAD-, n = 31). HDL GGE subfraction distributions, available in 125 subjects, were not significantly different among the groups. In contrast, dividing the whole study population into quartiles of serum triglyceride (TG) concentration showed that high TG levels were significantly associated with low HDL2b and high HDL3b concentrations. In a multivariate linear regression model, postheparin plasma hepatic lipase (HL) activity, and fasting serum insulin and TG concentrations were all associated independently and inversely with low HDL2b, but lipoprotein lipase or cholesteryl ester transfer protein activities were not correlated with HDL2b concentrations. Group 1 tended to have the smallest mean particle sizes in the HDL subfractions, significantly (P < 0.03, CAD vs. non-CAD) for HDL2b and for HDL2a. These differences were independent of TG, insulin and HL, but lost their significance when adjusted for beta-blocker therapy. Both HDL2 and HDL3 particles in group 1 were significantly depleted of unesterified cholesterol, and their HDL2 was TG-enriched (P = 0.053). A high HL activity, hyperinsulinemia and hypertriglyceridemia are independently associated with low levels of HDL2b and generally small HDL particle size. HDL particles in subjects with NIDDM and CAD are small-sized and have a low free cholesterol content. Both these characteristics may be markers of impaired reverse cholesterol transport.

Perceptions of spreading fats among women in Helsinki whose households use only butter or margarine.

This study sought to investigate whether women's perceptions about butter and soft margarine vary by the use of these fats. From interviews in 1984 with 102 middle-aged women from a follow-up dietary survey in Helsinki 27% of their households were classified as exclusive butter users, 46% used both butter and margarine and 27% used only margarine. The women evaluated margarine less "tasty" but "lighter", and "healthier" than butter. Women whose households used butter exclusively rated it more "useful" than those who used margarine, whereas women whose households used exclusively margarine rated it higher on taste than did exclusive butter users. Butter is a valued traditional food in Finland, and probably the taste of butter is still a reference standard for all spreads. Nevertheless some of the respondents had evidently come to like the soft vegetable margarine that was not available in their childhood.

The relative validity of reports of food intake of Dutch and Finnish boys aged 8 and 9 years.

Two studies were carried out to assess the relative validity of the techniques used in measuring the food intake during school lunch or home dinner of 30 Finnish and 68 Dutch boys aged 8 and 9 years. For each of the 30 Finnish boys, duplicate portions of three lunches provided to the boys were collected by a non-participating observer. Nutrient intakes were calculated with the use of a food composition table, and the results were compared with those from the records that were kept by the boys' mothers. For each of the 68 Dutch boys, duplicate portions of the hot meal, taken at home, were collected and analyzed chemically. The results were compared with those from the records that were kept by the boys' mothers. The mean values for the absolute intakes of energy and nutrients for the boys from both Finland and The Netherlands as reported by the boys themselves or their mothers were generally higher (15% to 35%) than those measured by chemical analysis of a duplicate portion or calculated from a weighed portion as collected by a non-participating observer. However, the results for the relative proportions of energy generally showed closer agreement (range of difference, +11% to -15%). The authors found in this study that collection of duplicate portions of food resulted in lower (3% to 15%) recorded food intakes in comparison with measurements recorded for meals consumed on other days.

Dietary intakes of mercury, lead, cadmium and arsenic by Finnish children.

In connection with the Multicenter Study on Atherosclerosis Precursors in Finnish Children, the dietary intakes of some toxic heavy metals were determined. The population of this study, conducted in five urban and 12 rural areas in Finland, consisted of 1768 children ages 3, 6, 9, 12, 15, and 18 years. Food consumption was measured by the 48-h recall method. The intakes of mercury, lead, cadmium, and arsenic were estimated using analytical data for the heavy metal content of Finnish foods. The total daily intakes of these four heavy metals increased with age. The energy-adjusted intakes of mercury, lead and arsenic were highest in the youngest age groups, whereas no change was observed in the mean cadmium intake expressed per 1000 kcal. Mean daily intakes of these metals per kg of body weight were three times higher in the 3-year-old children compared with the 18-year-olds. Cereals, potatoes and vegetables, and milk products were the main sources of these metals in the diet. Fruits and berries were also a significant source, especially in the youngest age groups. Consumption of fish was positively associated with intakes of mercury and arsenic, despite a contribution of only 1 per cent to the daily energy from this food group. The large standard deviations in the mean daily intakes of these metals indicate that exposure to these metals via diet is unevenly distributed among the Finnish children and adolescents. Further detailed evaluation of food patterns with a risk of high intakes of toxic heavy metals by children is needed.

Vitamin D status of children and adolescents in Finland.

3-,9- and 15-year-old children were studied in autumn in order to evaluate their serum 25-hydroxy-vitamin D (25-OH-D) concentration and their vitamin D intake. The 25-OH-D was significantly lower in the 15-year-old than in the other children, but it was satisfactory in all groups as compared to the 25-OH-D of healthy, young adults. The mean dietary vitamin D intake as well as the mean total vitamin D intake including supplements was low in all groups of children. With a vitamin D intake as low as in this study, every house-bound child would be at risk of vitamin D deficiency.

Fatty acid composition of serum cholesteryl esters in 3- to 18-year-old Finnish children and its relation to diet.

The composition of fatty acids in serum cholesteryl esters (CE) was analyzed gas chromatographically in 1348 boys and girls aged from 3 to 18 yr. A dietary survey was carried out simultaneously using the 48-h recall method. The dietary P/S ratio had highly significant correlations with CE fatty acids: positive with linoleate (0.567) and total omega 6 fatty acids and negative with saturated, monounsaturated, and omega 3 polyunsaturated fatty acids. The highest mean percentage of CE-linoleate was found in 15-yr-old girls (52.7, SD 4.68%) and lowest in 3-yr-old girls (48.1, SD 5.00%). Age, sex, and the degree of puberty had no independent effect on CE-linoleate after it had been adjusted for the effect of dietary P/S ratio by analysis of covariance. These results indicate that the fatty acid composition of serum CE depends on the quality of dietary fat and that CE-linoleate is a useful reflector of the dietary P/S ratio. The negative correlation between CE omega 3 fatty acids and dietary P/S ratio may be due to displacement of the omega 3 acids in serum CE by the much higher proportion of dietary linoleate.

Atherosclerosis precursors in Finnish children and adolescents. V. Fatty acid composition of serum cholesteryl esters: regional differences in Finland.

Fatty acid compositions of serum cholesteryl esters (CE) were analysed with gas chromatography from a total of 1,348 Finnish children. The study was a part of a comprehensive survey of atherosclerosis precursors among children, and included 3-, 6-, 9-, 12-, 15-, and 18-year-old children and adolescents from five urban and twelve rural communities in Finland. In all age groups and both sexes, the mean percentages of linoleate (CE-18:2) were lower and those of saturated and monounsaturated fatty acids higher in eastern rural areas than elsewhere. Eastern rural children also had significantly higher proportions of omega 3 polyunsaturated fatty acids in their serum CE's. The percentage of serum CE-18:2 parallels the P/S values obtained by a dietary survey from the same populations. The reason for higher percentages of the omega 3 fatty acids in rural communities cannot be explained by diet, and remains unclear.

Atherosclerosis precursors in Finnish children and adolescents. VIII. Food consumption and nutrient intakes.

A dietary survey was conducted in 1980 in connection with the Multicentre Study on Atherosclerosis Precursors in Finnish Children in five urban and 12 rural communes in various parts of Finland. 1,768 children aged 3, 6, 9, 12, 15 and 18 years were interviewed using the 48 hour recall method. Food consumption, and the intakes of energy and 49 nutrients were calculated. The intakes of energy and most nutrients increased in the successive age groups until the age of 15 years. There were only small differences in the diet of children belonging to different social classes. Protein accounted for 14% of total energy intake, fat for 38%, total carbohydrate for 48%, and sucrose for 10%. The ratio of polyunsaturated and saturated fatty acids in the diet (P/S) was 0.24 for the whole material, which is higher than found in previous studies in Finland. The P/S ratio was higher in urban areas and West Finland than in rural areas and in East Finland. The share of fat of energy intake exceeded the recommendation given by the Ministry of Health and the P/S ratio was lower than recommended. The mean daily intakes of energy and vitamins met the recommendations. Of the mineral elements, the intakes of calcium, phosphorus, potassium, magnesium and manganese were abundant. The intakes of iron, copper, zinc, molybdenum and chromium were lower than recommended in most age groups and the intakes of selenium and fluorine in all age groups. The large share of refined foods in the children's diet was the main reason for the low nutrient densities.

The vitamin D intake of children and adolescents in Finland.

The vitamin D intake from diet and supplements was studied in 1768 children and adolescents aged 3, 6, 9, 12, 15 and 18 years in the autumn of 1980. The dietary vitamin D intake increased with increasing age, being lowest in the two youngest groups and highest in the two oldest groups, whereas the use of supplements decreased with increasing age. The total vitamin D intake, including both dietary vitamin D and vitamin D obtained from supplements was highest in the youngest groups and decreased with age. In all groups both the dietary mean vitamin D intake and the mean total intake were well below the recommended dietary allowance. The total amount of vitamin D in the diet was lowest in the two youngest groups and the 12-year-olds and highest in the 9-year-olds and the two oldest groups. The main dietary sources of vitamin D were vitaminized margarine, fish and fish products and eggs, providing together about 80 per cent of the total vitamin D intake. With a vitamin D intake as low as that found in this study, ranging from 2.5 to 5.1 micrograms/d including supplements, the risk of nutritional rickets should be high. Nutritional rickets is, however, uncommon in these age groups. The children in this study were healthy, active individuals abundantly exposed to sunshine and therefore getting enough vitamin D through the endogenous route in the skin. Every house-bound child could, however, be at risk of developing vitamin D deficiency with such a low vitamin D intake.