Socioeconomic differences in smoking trends among pregnant women at first antenatal visit in Sweden 1982-2001: increasing importance of educational level for the total burden of smoking.

BACKGROUND: There was a decrease in smoking during early pregnancy in Swedish women between 1982 and 2001. We sought to determine whether there was a parallel decrease in socioeconomic inequality in smoking. METHODS: Registry data indicating educational level and smoking status at first antenatal visit in all 2,022,469 pregnancies in Sweden 1982-2001 were analysed. Prevalence differences, odds ratios based on prevalences and total attributable fractions were compared for five-year intervals. RESULTS: The prevalence differences of smoking showed a greater decrease at the lowest and middle educational level compared with the highest educational level (14.5%, 15.7% and 10.2%, respectively) indicating reduced inequality in absolute terms. However, odds ratios regarding low educational attainment versus high, increased from 5.6 to 14.2, signifying increased inequality in relative terms. Moreover, the total attributable fraction of low and intermediate educational level regarding smoking at first antenatal visit increased from 61% to 76% during the period studied. CONCLUSIONS: Smoking at first antenatal visit in Sweden between 1982 to 2001 decreased in a way that conclusions regarding trends in inequalities in smoking at first antenatal visit depend on the type of measure applied. However, using the measure of total attributable fraction, which takes into consideration the impact of the exposure on the individual as well as the effect of the varying size of the group of exposed, the growing importance of educational level for the behaviour in the population was demonstrated.

Biocompatible materials developments for new medical implants.

Recent work on modifying silicone rubber to improve water permeability and biocompatibility is described. In addition, modifications to the interface between an active implanted device and the body are reported, which have led to reduced power consumption and improved device performance.

The effect of gluconeogenesis on phospholipid turnover in isolated chick proximal tubule cells.

Previous work from this laboratory has shown that isolated chick renal proximal tubule cells possess an Na+-dependent Pi transport system and that Pi uptake is stimulated under gluconeogenic conditions. It is shown in the present paper that gluconeogenesis is associated with a rapid incorporation of Pi into membrane phospholipids, particularly phosphatidylinositol, and some evidence has been obtained for a change in the relative amounts of phosphatidylinositol polyphosphates under gluconeogenic conditions. There is no increase in the total phospholipid phosphate content however, suggesting that pyruvate-induced incorporation of Pi into phospholipids represents accelerated turnover rather than a net increase in synthesis. It is suggested that the stimulation of Na+-dependent Pi uptake by pyruvate is related to the increased rate of phospholipid turnover. Thus Pi transport may be a further example of a physiological system that is influenced by phosphatidylinositol metabolism. The role of phosphatidylinositol phosphates could be to stimulate transfer of transporter molecules from internal stores to the brush-border membrane of the cell.

Activation by reduction of the resting form of cytochrome c oxidase: tests of different models and evidence for the involvement of CuB.

(1) The reaction of the resting form of oxidised cytochrome c oxidase from ox heart with dithionite has been studied in the presence and absence of cyanide. In both cases, cytochrome a reduction in 0.1 M phosphate (pH 7) occurs at a rate of 8.2.10(4) M-1.s-1. In the absence of cyanide, ferrocytochrome a3 appears at a rate (kobs) of 0.016 s-1. Ferricytochrome a3 maintains its 418 nm Soret maximum until reduced. The rate of a3 reduction is independent of dithionite concentration over a range 0.9 mM-131 mM. In the presence or cyanide, visible and EPR spectral changes indicate the formation of a ferric a3/cyanide complex occurs at the same rate as a3 reduction in the absence of cyanide. A g = 3.6 signal appears at the same time as the decay of a g = 6 signal. No EPR signals which could be attributed to copper in any significant amounts could be detected after dithionite addition, either in the presence or absence of cyanide. (2) Addition of dithionite to cytochrome oxidase at various times following induction of turnover with ascorbate/TMPD, results in a biphasic reduction of cytochrome a3 with an increasing proportion of the fast phase of reduction occurring after longer turnover times. At the same time, the predominant steady state species of ferri-cytochrome a3 shifts from high to low spin and the steady-state level of reduction of cytochrome a drops indicating a shift in population of the enzyme molecules to a species with fast turnover. In the final activated form, oxygen is not required for fast internal electron transfer to cytochrome a3. In addition, oxygen does not induce further electron uptake in samples of resting cytochrome oxidase reduced under anaerobic conditions in the presence of cyanide. Both findings are contrary to predictions of certain O-loop types of mechanism for proton translocation. (3) A measurement of electron entry into the resting form of cytochrome oxidase in the presence of cyanide, using TMPD or cytochrome c under anaerobic conditions, shows that three electrons per oxidase enter below a redox potential of around +200 mV. An initial fast entry of two electrons is followed by a slow (kobs approximately 0.02 s) entry of a third electron.(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism.

Lack of a direct role for cyclic AMP in parathyrin action on phosphate reabsorption by the kidney.

Isolated chick kidney proximal tubule cells have been used in a study of the mechanism by which PTH inhibits Na+-dependent Pi transport in the kidney. Treatment with PTH inhibits Pi uptake by the cells by 13% and stimulates cyclic AMP production by 77%. Forskolin, a potent activator of adenyl cyclase, brought about an 11-fold stimulation of cyclic AMP production by the cells, but in contrast to PTH, the drug had no effect on Na+-dependent Pi uptake. These results provide evidence that PTH action on phosphate transport is not mediated by cyclic AMP.

On the adaptive significance of stress-induced immunosuppression.

We approach the field of stress immunology from an ecological point of view and ask: why should a heavy physical workload, for example as a result of a high reproductive effort, compromise immune function? We argue that immunosuppression by neuroendocrine mechanisms, such as stress hormones, during heavy physical workload is adaptive, and consider two different ultimate explanations of such immunosuppression. First, several authors have suggested that the immune system is suppressed to reallocate resources to other metabolic demands. In our view, this hypothesis assumes that considerable amounts of energy or nutrients can be saved by suppressing the immune system; however, this assumption requires further investigation. Second, we suggest an alternative explanation based on the idea that the immune system is tightly regulated by neuroendocrine mechanisms to avoid hyperactivation and ensuing autoimmune responses. We hypothesize that the risk of autoimmune responses increases during heavy physical workload and that the immune system is suppressed to counteract this.

Good genes, oxidative stress and condition-dependent sexual signals.

The immune and the detoxication systems of animals are characterized by allelic polymorphisms, which underlie individual differences in ability to combat assaults from pathogens and toxic compounds. Previous studies have shown that females may improve offspring survival by selecting mates on the basis of sexual ornaments and signals that honestly reveal health. In many cases the expression of these ornaments appears to be particularly sensitive to oxidative stress. Activated immune and detoxication systems often generate oxidative stress by an extensive production of reactive metabolites and free radicals. Given that tolerance or resistance to toxic compounds and pathogens can be inherited, female choice should promote the evolution of male ornaments that reliably reveal the status of the bearers' level of oxidative stress. Hence, oxidative stress may be one important agent linking the expression of sexual ornaments to genetic variation in fitness-related traits, thus promoting the evolution of female mate choice and male sexual ornamentation, a controversial issue in evolutionary biology ever since Darwin.

MHC genotype and male ornamentation: genetic evidence for the Hamilton-Zuk model.

The major histocompatibility complex (MHC) is an immunologically important cluster of highly variable genes that is known to affect fitness in domesticated mammals and birds. Spur length of male pheasants in southern Sweden correlates with male viability, female mate choice, and offspring survival rate. Here we show by genetic analyses that the MHC genotype is associated with variation in both male spur length and male viability. These are the first data that directly support a 'good genes' hypothesis by Hamilton and Zuk predicting that females discriminate among males on the basis of secondary sexual characters in order to pass on genes for disease resistance that improve fitness in their offspring.

Association between major histocompatibility complex class IIB alleles and resistance to Aeromonas salmonicida in Atlantic salmon.

We have tested the importance of genetic variation in the major histocompatibility complex (MHC) class IIB in Atlantic salmon (Salmo salar) for survival after challenge with a highly virulent bacterial pathogen. Forty juvenile full siblings from each of 120 families were infected with the bacterium Aeromonas salmonicida, which causes high mortality in salmon due to furunculosis. Fishes from high-resistance (HR, < 35% mortality) and low-resistance (L,R, > 80% mortality) families were screened for their MHC class IIB genotypes using the denaturing gradient gel electrophoresis (DGGE) technique. The exon 2 sequences, encoding the major part of the peptide-binding region, were established for each DGGE fragment. One allele, e, containing a missense single base substitution was significantly more prevalent in HR families than in LR families. An odds-ratio test showed that broods carrying this allele had a 12-fold higher chance of being HR than broods without the e allele. A second allele, i, showed significantly higher frequencies in uninfected and surviving individuals than in infected dead individuals. A third allele, j, tended to more prevalent both in LR families and in individuals that had died of the infection. There was no correlation between MHC heterozygosity and resistance to A. salmonicida. Our results support the hypothesis that MHC polymorphism is maintained through pathogen-driven selection acting by means of frequency-dependent selection rather than heterozygous advantage.

Haematoporphyrin derivative--photodynamic therapy of colorectal carcinoma, sensitized using verapamil and adriamycin.

The p-glycoprotein export mechanism may have an effect on the cytotoxicity of chemotherapy or photodynamic therapy (PDT) by reducing cytotoxic drug or photosensitizer concentration within cells. In tissues over-expressing this protein, modulation with verapamil (an antagonist of p-glycoprotein) may be useful in reversing this form of treatment resistance. This study examined the bioactivity of the interaction of photodynamic therapy using Haematoporphyrin derivative (HpD), chemotherapy and the response modifier verapamil. Multicellular spheroids derived from the human colorectal cancer line HRT 18 were used in vitro and bioactivity assessed using growth retardation. Bioactivity was observed to be greatest when all three agents and light irradiation were combined. This application may be clinically useful in the treatment of colorectal carcinoma by improving the efficacy of PDT using HpD.

Adjuvant intraoperative photodynamic therapy for colorectal carcinoma: a clinical study.

The local recurrence rate of colorectal carcinoma after surgery is unacceptable in most series, and adjuvant therapies have made only a small impact on this. There is experimental evidence that adjuvant intraoperative photodynamic therapy (AIOPDT) may be effective. AIOPDT involves systematically photosensitizing the patient preoperatively with a drug (HpD) which relatively localizes to tumour and is activated using visible light. At operation the resected tumour bed is illuminated with a predetermined uniform light energy density to eradicate microscopic tumour deposits left at the lateral resection margin. We have previously investigated technical and biological factors leading to this clinical trial. Seventeen patients have received AIOPDT in a potentially effective dose, and safety and technical matters have been investigated. Cutaneous phototoxicity occurred in 3 patients. Three patients had anastomotic breakdown, none considered attributable to PDT. The intraoperative technique was a practical option. AIOPDT carried a low patient morbidity and should be investigated in prospective clinical trials to determine if local recurrence rates can be decreased.

Distribution of temoporfin, a new photosensitizer for the photodynamic therapy of cancer, in a murine tumor model.

The biodistribution of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a recently developed photosensitizer, was investigated in BALB/c mice. The drug was administered intravenously (0.35-0.75 mumol/kg) to tumor-free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood and tissue samples were collected for up to 96 h post-dose. Drug concentrations were determined by HPLC coupled to photometric detection at 423 nm. Concentrations in blood and liver fell relatively rapidly such that blood concentrations at later time points were below the limit of detection. Tumor concentrations rose at first and then remained constant from 24 h. Temoporfin concentrations in some tissues, notably heart and skeletal muscle, declined only slowly when compared to blood. The tumor: tissue ratios for those organs that showed a more rapid decline in temoporfin concentrations were higher at later times, whereas in tissues such as muscle the ratio remained relatively constant. The organs with the highest tumor:tissue ratios were small intestine (8.6), liver (6.9) and skeletal muscle (5.0).

Distribution and excretion of radiolabeled temoporfin in a murine tumor model.

The biodistribution and excretion of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a recently developed photosensitizer, was investigated in BALB/c mice. [14C]temoporfin was administered intravenously (0.73 mumol/kg) to tumor-free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood, tissue and fecal samples were collected for 35 days and 10 days postdose from tumor-free mice and tumor-bearing mice, respectively. Blood concentrations fell rapidly such that at later time points they were indistinguishable from background counts. Tumor concentrations rose to a peak of 0.34 microgram temoporfin equivalents/mL at 2 days and then declined in parallel (log plot) with the blood concentrations. Tumor: tissue ratios at 2 days for skin, adipose tissue and skeletal muscle underlying the tumor were 1.5, 2.3 and 3.8, respectively. By 4 days the corresponding values were 1.6, 3.4 and 4.0. Nearly 40% of the administered radioactivity was excreted in the feces in the first 24 h and more than 80% had been excreted by 20 days. Less than 0.2% of the dose was recovered from the urine. An elimination half-life of 10-12 days was calculated from the excretion data.

In vivo photodynamic characteristics of the near-infrared photosensitizer 5,10,15,20-tetrakis(M-hydroxyphenyl) bacteriochlorin.

This paper describes the photodynamic characteristics of the new near-infrared photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC or SQN400) in normal rat and mouse tissues. A rat liver model of photodynamic tissue necrosis was used to determine the in vivo action spectrum and the dose-response relationships of tissue destruction with drug and light doses. The effect of varying the light irradiance and the time interval between drug administration and light irradiation on the biological response was also measured in the rat liver model. Photobleaching of mTHPBC was measured and compared with that of its chlorine analog (mTHPC) in normal mouse skin and an implanted mouse colorectal tumor. The optimum wavelength for biological activation of mTHPBC in rat liver was 739 nm. mTHPBC was found to have a marked drug-dose threshold of around 0.6 mg kg-1 when liver tissue was irradiated 48 h after drug administration. Below this administered drug dose, irradiation, even at very high light doses, did not cause liver necrosis. At administered doses above the photodynamic threshold the effect of mTHPBC-PDT was directly proportional to the product of the drug and light doses. No difference in the extent of liver necrosis produced by mTHPBC was found on varying the light irradiance from 10 to 100 mW cm-2. The extent of liver necrosis was greatest when tissue was irradiated shortly after mTHPBC administration and necrosis was absent when irradiation was performed 72 h or later after drug administration, suggesting that the drug was rapidly cleared from the liver. In vivo photobleaching experiments in mice showed that the rate of bleaching of mTHPBC was approximately 20 times greater than that of mTHPC. It is argued that this greater rate of bleaching accounts for the higher photodynamic threshold and this could be exploited to enhance selective destruction of tissues which accumulate the photosensitizer.

Biodistribution and bioactivity of tetra-pegylated meta-tetra(hydroxyphenyl)chlorin compared to native meta-tetra(hydroxyphenyl)chlorin in a rat liver tumor model.

It has been proposed that the construction of a photosensitizer-polymer conjugate would lead to an increased selective retention of the drug in tumor tissue resulting in an enhancement of selective tumor destruction by light in photodynamic therapy. In this study the kinetics of a tetra-pegylated derivative of meta-tetra(hydroxyphenyl)chlorin (mTHPC-PEG) were compared with those of native meta-tetra(hydroxyphenyl)chlorin (mTHPC) in a rat liver tumor model. In addition, the time course of bioactivity of both drugs was studied in normal liver tissue. Pegylation of mTHPC resulted in a two-fold increase in the plasma half-life time, a five-fold decrease in liver uptake and an increase in the tumor selectivity at early time intervals after drug administration. However, although mTHPC concentrations in liver decrease rapidly with time, mTHPC-PEG liver concentrations increased as a function of time. This led to a loss of tumor selectivity at all but the earliest time points, whereas with mTHPC tumor selectivity increased with time. For both drugs the time course of bioactivity in the liver parallels drug concentration levels with extensive necrosis after irradiation of mTHPC-PEG-sensitized liver tissue up to drug-light intervals of 120 h. It is concluded that on balance mTHPC-PEG does not appear to show any benefits over native mTHPC for the treatment of liver tumors, as normal liver tissue accumulates the compound. However, pegylation is a potentially promising strategy with an increase in tumor selectivity and reduced liver uptake if accumulation in the liver can be prevented.

Modulation of phosphate accumulation in isolated chick kidney cells by gluconeogenic substrates.

An isolated proximal-tubule preparation is described that accumulates Pi in a saturatable, Na+-dependent manner. The initial rate of Pi accumulation is greater in cells incubated with the gluconeogenic substrates pyruvate and lactate than in cells incubated with glucose. Glucose was produced from the substrates under these conditions. Incubation with either NAD+ or NADH inhibits the initial rate of Pi accumulation. These data provide evidence that the effects of gluconeogenesis on Pi uptake are not mediated by the oxidation state of the nicotinamide coenzymes.

Effect of dietary fat on individual long-chain fatty acyl-CoA esters in rat liver and skeletal muscle.

The effect of dietary fat on the long-chain acyl-CoA ester profile of liver and skeletal muscle was investigated by feeding weanling rats 12%-fat diets composed of high-linoleic safflower oil (73% 18:2n-6), high-oleic safflower oil (70% 18:1n-9) or olive oil (70% 18:1n-9) for six and ten weeks. Approximately 50% of both hepatic and skeletal muscle acyl-CoA esters comprised linoleoyl-CoA or oleoyl-CoA with high-linoleic or oleic feeding, respectively. Total hepatic acyl-CoA ester concentration was 40% higher (p less than 0.05) in rats fed 12% fat compared with controls fed a 4%-fat diet. These data demonstrate that the long-chain acyl-CoA ester profile of liver and skeletal muscle reflects the dietary fatty acid profile.

The effect of polymer adsorption on the wetting properties of partially hydrophobized magnetite.

Upon reverse flotation of iron ore, the surface of the iron ore concentrate may become partially hydrophobized due to adsorption of flotation collector, which is facilitated by the calcium ions present in the process water. Hydrophobic areas on the concentrate surface may introduce problems in subsequent pelletization of the concentrate. A possible way to restore the wettability of the surface could be by modifying the surface with a hydrophilic polymer. The effect of hydrophilic polymers of different types, viz. cationic, anionic, and non-ionic, on the wettability of the magnetite surface after adsorption of a surfactant was investigated. Although all the polymers could adsorb on magnetite at pH 8.5, the contact angle measurements revealed that only anionic ammonium polyacrylate could decrease the contact angle of synthetic magnetite after surfactant adsorption to a level close to that of as-synthesized magnetite. Such effect was probably achieved due to shielding of the hydrophobic surfactant chains from the aqueous phase by hydrophilic polyacrylate molecules. The fact that polyacrylate adsorption on magnetite occurred via calcium ions makes polyacrylate suitable for application in calcium-rich process water. The results presented in this work illustrate that ammonium polyacrylate could be successfully used to improve the wettability of magnetite after adsorption of surfactants.

The effect of calcium ions and sodium silicate on the adsorption of a model anionic flotation collector on magnetite studied by ATR-FTIR spectroscopy.

Previous studies have shown that agglomeration of the magnetite concentrate after reverse flotation of apatite is negatively affected by the collector species adsorbed on the surface of magnetite. In this work, the effect of ionic strength, calcium ions and sodium silicate on the unwanted adsorption of a model anionic flotation collector on synthetic magnetite was studied in situ using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The amount of collector adsorbed was found to increase with increasing ionic strength at pH 8.5 providing evidence to the contribution of electrostatic forces to the adsorption of the collector. Adding sodium silicate to the system resulted in a threefold decrease in the amount of collector adsorbed compared to when no sodium silicate was added, confirming the depressing activity of sodium silicate on magnetite. Calcium ions were shown to increase the adsorption of both the collector and sodium silicate on magnetite. The depressing effect of sodium silicate on collector adsorption was completely suppressed in the presence of calcium ions under the conditions studied. Furthermore, the amount of collector adsorbed on magnetite from the silicate-collector solution increased 14 times upon addition of calcium ions suggesting that calcium ions in the process water may increase undesired adsorption of the collector on the iron oxide.