[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

Objective

Inflammation is an important contributor to atherosclerosis progression. A glucose analogue ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [¹⁸F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [¹⁸F]FDG to various stages of coronary plaques in a pig model.

Methods

First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [¹⁸F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).

Results

Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [¹⁸F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).

Conclusions

We found increased uptake of [¹⁸F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [¹⁸F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.     

Physical mapping of three fruit ripening genes：Endopolygalacturonase,ACC oxidase and ACC synthase from apple（Malus x domestica） in an apple rootstock A106（Malus sieboldii

The apple rootstock,A106(Malus sieboldii),had 17 bivalents in pollen mother cells at meiotic metaphase 1,and 17 chromosomes in a haploid pollen cell.Karyotypes were prepared from root-tip cells with 2n=34 chromosomes,Seven out of 82 karyotypes(8.5%) showed one pari of satellites at the end of the short arm of chromosome 3.C-bands were shown on 6 pairs of chromosomes 2,4,6,8,14,and 16 near the telomeric regions of short arms.Probes for three ripening-related genes from Malus x domestica:endopolygalacturonase(EPG,0.6kb),ACC oxidase(1.2kb),and ACC synthase(2kb)were hybridized in situ to metaphase chromosomes of A106.Hybridization sites for the EPG gene were observed on the long arm of chromosome 14 in 15 out of 16 replicate spreads and proximal to the centromere of chromosomes 6 and 11.For the ACC oxidase gene,hylridization sites were observed in the telomeric region of the short arm of chromosomes 5 and 11 in 87% and 81% of 16 spreads respectively,proxiaml to the centromere of chromosome 1 in 81% of the spreads,and on the long arm of chromosome 13 in 50% of the spreads. Physical mapping of three fruit ripening genes in an apple rootstock A106.Twenty five spreads were studied for the ACC synthase gene and hybridization sites were observed in the telomeric region of the short arm of chromosome 12 in 96% of the spreads.chromosomes 9 and 10 in 76% of the spreads,and chromosome 17 in 56% of the spreads.     

Occurrence of esterified triterpenoid alcohols in the leaves of Pilosella officinarum

The mature winter leaves of Pilosella officinarum coll. Schultz and Schultz contained 29 mg esterified triterpenoid alcohols (g dry weight)⁻¹, of which over 80% was esterified with long-chain (C16-C18) fatty acids. The major fatty acids were 16:0, 18:2ω6 and 18:3ω3 and their amounts varied according to the season and stage of leaf development. In mature leaves the amount of triterpenoid alcohols esterified with long-chain fatty acids varied only slightly with the season. The changes in the fatty acid proportions in late winter-early spring, however, indicated a turnover in the esterified triterpenoid alcohol pool. In late winter after the snow had melted a 50% decrease occurred in the amount of triterpenoid alcohols esterified with short-chain fatty acids. The amount of esterified triterpenoid alcohols in immature leaves was relatively low [4 mg (g dry weight)⁻¹].
In the mature leaves esterified triterpenoid alcohols were found in globules whose appearance varied greatly according to the season. The globules were partly dissolved in late winter, and this together with the activation of respiration, suggests that the globules function as short-term energy reservoirs. Relationships between the appearance of lipid globules and the amount of esterified triterpenoid alcohols are discussed.     

Smoking during pregnancy is associated with a decreased incidence of obstetric anal sphincter injuries in nulliparous women

Background

Smoking is a modifiable lifestyle factor that has been shown to be associated with adverse perinatal outcomes and to have adverse health and dose-dependent connective tissue effects. The objective of this study was to examine whether smoking during pregnancy was associated with the incidence of obstetric anal sphincter injuries (OASIS) among six birthweight groups in singleton vaginal deliveries, considering nulliparous and multiparous women separately between 1997 and 2007 in Finland.

Methodology

A retrospective population-based register study. Populations included women with spontaneous singleton vaginal deliveries, consisting of all 213,059 nulliparous and all 288,391 multiparous women. Incidence of OASIS (n = 2,787) between smoking status groups was adjusted using logistic regression analyses.

Principal Findings

Of the nulliparous women, 13.1% were smokers, 3.6% had given up smoking during the first trimester of their pregnancy and 81.1% were non-smokers. Among these groups 0.7%, 0.9% and 1.1%, respectively suffered OASIS (p≤0.001). Nulliparous women who smoked had a 28% (95% CI 16–38%, p≤0.001) lower risk of OASIS compared to non-smokers, when adjusting for background variables. In multiparous women, the overall frequencies of OASIS were much lower (0.0–0.2%). A similar inverse relationship between OASIS rates and smoking was significant in pooled univariate analysis of multiparous women, but multivariate analysis revealed statistically insignificant results between non-smokers and smokers.

Conclusions

Nulliparous women who were smokers had a 28% lower incidence of OASIS. However, smoking during pregnancy cannot be recommended since it has shown to be associated with other adverse pregnancy outcomes and adverse health effects. The observed association warrants clinical repetition studies and, if confirmed, also in vitro studies focusing on connective tissue properties at a molecular and cellular level.     

Activity changes of inorganic pyrophosphatase of Streptococcus faecalis during batch culture

The state of inorganic pyrophosphatase (EC 3.6.1.1) from Streptococcus faecalis ATCC 8043 was studied in different phases of batch culture. The degree of inactivation (i.e. the ratio of activities observed before and after incubation at 37 degrees C without cysteine) was highest, and the degree of activation (i.e. the ratio of activities after and before incubation in the presence of cysteine) was lowest, in samples taken during the early-exponential growth phase. During the various phases of batch culture, the specific activity before incubation and the degree of inactivation changed in parallel, whereas the specific activity observed after incubation remained nearly constant. During the early-exponential phase of growth almost all the enzyme was in the high-activity form, whereas during the stationary phase the highly active and the less active forms existed in equal amounts. These findings suggest that inorganic pyrophosphatase in S. faecalis is synthesized constitutively and is primarily regulated at the level of activity.     

Early Life Stress and Physical and Psychosocial Functioning in Late Adulthood

Background

Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II.

Methods

The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934–44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes.

Results

Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = −0.40, 95% confidence interval [95% CI]: −0.71 to −0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = −0.89, 95% CI: −1.58 to −0.20) and (b = −0.65, 95% CI: −1.25 to −0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = −0.70, 95% CI: −1.35 to −0.06). These differences in physical and psychosocial functioning were not observed among women.

Conclusion

Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.     

Maternal Use of Selective Serotonin Reuptake Inhibitors and Lengthening of the Umbilical Cord: Indirect Evidence of Increased Foetal Activity—A Retrospective Cohort Study

BackgroundAntenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood.MethodsWe analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002–2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes.ResultsAltogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p < 0.0001) and 5 minutes (p < 0.0001) and more admissions to the neonatal intensive care unit (p < 0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p < 0.0001) than non-exposed newborns.ConclusionIn addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.     

Comparison between low- and standard-dose ACTH tests in premature infants at risk for chronic lung disease

In order to find a sensitive method to evaluate adrenocortical function in premature infants, we compared low- (0.5 microg/1.73 m(2)) and standard-dose (250 microg/1.73 m(2)) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low-birth-weight infants before and 2 days after the end of dexamethasone therapy (duration 9-14 days) for chronic lung disease. Basal serum cortisol levels were inappropriately low in several infants already before dexamethasone therapy (median 190, range 60-357 nmol/l). The 95% confidence intervals of mean serum cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low-dose gave a clearly lower response than the standard-dose test. The LD-ACTH can be used in premature infants as in older children and adults, but the criteria for adrenocortical insufficiency need to be defined.     

A site-directed mutagenesis study on Escherichia coli inorganic pyrophosphatase. Glutamic acid-98 and lysine-104 are important for structural integrity, whereas aspartic acids-97 and -102 are essential for catalytic activity

Analysis of the conservation of functional residues between yeast and Escherichia coli inorganic pyrophosphatases (PPases) suggested that Asp-97, Glu-98, Asp-102, and Lys-104 are important for the action of E. coli PPase [Lahti, R., Kolakowski, L. F., Heinonen, J., Vihinen, M., Pohjanoksa, K., & Cooperman, B. S. (1990) Biochim. Biophys. Acta 1038, 338-345]. We replaced these four residues by oligonucleotide-directed mutagenesis, giving variant PPases DV97, DE97, EV98, DV102, DE102, KI104, and KR104. PPase variants DV97, DV102, and KI104 had no enzyme activity, whereas PPase variants DE97, EV98, DE102, and KR104 had 22%, 33%, 3%, and 3% of the wild-type PPase activity, respectively. This suggests that Asp-97, Asp-102, and Lys-104 are essential for the catalytic activity of E. coli PPase. PPase variants DV98 and KR104 also had an increased sensitivity to heat denaturation; incubation of these mutant PPases at 75 degrees C for 15 min in the presence of 5 mM magnesium ion decreased the activity to 20% and 1%, respectively, of the initial value while 74% of the activity was observed with wild-type PPase. Furthermore, these thermolabile mutant PPases displayed the most profound conformational changes of the PPase variants examined, as demonstrated by the binding of the fluorescent dye Nile red that monitors the hydrophobicity of protein surfaces. Accordingly, Glu-98 and Lys-104 seem to be important for the structural integrity of E. coli PPase.