Plasma adiponectin concentrations and placental adiponectin expression in pre-eclamptic women

This study was conducted to compare maternal plasma adiponectin concentrations and adiponectin expression in term placentas between normotensive pregnant women and pre-eclamptic women. Plasma adiponectin concentrations were assessed by a sandwich enzyme-linked immunosorbent assay in 81 normotensive pregnant women, 27 pre-eclamptic women and 15 non-pregnant healthy women. The expression of adiponectin in the placentas was assessed by immunohistochemistry. Plasma adiponectin concentrations in normotensive pregnant women did not show a significant change during pregnancy and postpartum compared with non-pregnant women. However, plasma adiponectin concentrations in pre-eclamptic women were significantly (p < 0.05) lower than in non-pregnant and normotensive pregnant women. No immunoreactive adiponectin was detected in the term placentas of normotensive pregnant women, whereas a positive immunostaining for adiponectin was observed in endothelial cells of chorionic vessels in pre-eclamptic women. Our data suggest that decreased plasma adiponectin concentrations may contribute to the pathophysiology of pre-eclampsia and that adiponectin localized in chorionic vessels may play a role in the restoring of endothelial damage in the feto-maternal units of pre-eclampsia.     

Determining a methodology of dosimetric quality assurance for commercially available accelerator-based boron neutron capture therapy system

The irradiation field of boron neutron capture therapy (BNCT) consists of multiple dose components including thermal, epithermal and fast neutron, and gamma. The objective of this work was to establish a methodology of dosimetric quality assurance (QA), using the most standard and reliable measurement methods, and to determine tolerance level for each QA measurement for a commercially available accelerator-based BNCT system. In order to establish a system of dosimetric QA suitable for BNCT, the following steps were taken. First, standard measurement points based on tissue-administered doses in BNCT for brain tumors were defined, and clinical tolerances of dosimetric QA measurements were derived from the contribution to total tissue relative biological effectiveness factor-weighted dose for each dose component. Next, a QA program was proposed based on TG-142 and TG-198, and confirmed that it could be assessed whether constancy of each dose component was assured within the limits of tolerances or not by measurements of the proposed QA program. Finally, the validity of the BNCT QA program as an evaluation system was confirmed in a demonstration experiment for long-term measurement over 1 year. These results offer an easy, reliable QA method that is clinically applicable with dosimetric validity for the mixed irradiation field of accelerator-based BNCT.     

Copper Biology in Health and Disease: Recent advances in copper analyses by inorganic mass spectrometry

Copper (Cu) participates in the biological redox reaction in the body, and its deficiency is fatal to the body. At the same time, Cu is extremely toxic when it exists in excess. Thus, the body has to tightly and spatiotemporally regulate the concentration of Cu within a physiological range by several groups of Cu-regulating proteins. However, entire mechanisms underlying the maintenance of Cu homeostasis in body and cells have not fully understood. It is necessary to analyze Cu itself in a body and in a cell to reveal the Cu homeostasis. In this review, recent advances in the analytical techniques to understand the Cu metabolism such as speciation, imaging and single-cell analysis of Cu were highlighted.     

Recombinant human lactoferrin has a potential to suppresses uterine cervical ripening in preterm delivery in animal model

Objective To investigate the effect of recombinant human lactoferrin (rhLF) on cervical ripening using a rabbit model in which preterm labor was induced by bacterial endotoxin lipopolysaccharide (LPS). Study design Timed pregnant rabbits (New Zealand White, 3–4 kg, day 14) were randomly assigned to the following treatment groups: Group A, LPS + rhLF (n = 4); Group B, LPS (n = 4); and Group C, control (n = 4). Recombinant human lactoferrin (10 μg) was administrated to pregnant rabbits in Group A and not in Group B. Lipopolysaccharide (100 μg) was given to the rabbits in both groups for 3 days (days14–16). Drugs were administered as a vaginal suppository. On day 18, the rabbits were anesthetized with intramuscular ketamine hydrochloride (20 mg/kg) and diazepam (4 mg/kg). Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution for a histological study with standard hematoxylin-eosin staining. The other was used for an extension test to assess the grade of ripening. Extension was measured after a 5-mm length of cervical tissue was loaded with 5.8 g. Results The histological study showed remarkably loose and edematous connective tissue in Group B cervices. Cervical tissues in Group A was not different from those in Group C. Extension lengths were 2.2 ± 0.2 mm in Group A, 7.0 ± 2.7 mm in Group B, and 1.7 ± 0.3 mm in Group C. Conclusion These results suggest that rhLF inhibits cervical maturation induced by LPS in a rabbit model and may have a potential to prevent preterm delivery caused by cervical infection and ripening.     

Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population

Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population. The authors compare the genotype distributions and allele frequencies of the EGFR +2073 A/T and HER2 +655 A/G polymorphisms in 116 endometrial cancer patients and 213 controls using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. RFLP results were confirmed by direct DNA sequencing. Of the 116 patients, 76 (65.5%) could be followed up. Disease-free survival estimates were computed using the Kaplan-Meier method, and differences between survival periods were assessed using the log-rank test. No significant differences were observed in either genotype distributions or allele frequencies in the EGFR +2073 A/T and HER2 +655 A/G polymorphisms between endometrial cancer patients and controls. The stratification by histological types and staging failed to identify significant differences between endometrial cancer patients and controls. No statistical differences were noted between these polymorphisms and disease-free survival (Kaplan-Meier log-rank test P = .55 and .66, for the EGFR +2073 A/T and HER2 +655 A/G, respectively). These results suggest that the EGFR +2073 A/T and HER2 +655 A/G polymorphisms are not associated with endometrial cancer in a Japanese population. These conclusions are based on relatively small numbers and will require verification from additional independent studies.     

Role of tumor necrosis factor-alpha and interleukin-1beta on lung dysfunction following hemorrhagic shock in rats.

BACKGROUND: Hemorrhagic shock occasionally causes a fatal outcome following an outbreak of lung dysfunction, but the precise mechanism has not been clearly elucidated. Several studies have indicated that hemorrhagic shock causes a delayed vascular inflammatory decompensation and leads to inflammation-related organ dysfunction. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are known as major proinflammatory cytokines that play an important role in excessive autolytic inflammation, finally inducing organ dysfunctions. In this study, the role of TNF-alpha and IL-1beta on lung dysfunction following hemorrhagic shock was examined by using FR167653, a potent inhibitor of TNF-alpha and IL-1beta production that acts by suppressing p38 mitogen-activated protein kinase (MAPK). MATERIAL/METHODS: Hemorrhagic shock was induced in anesthetized male rats by bleeding via a common carotid catheter for 20 minutes to 25% of total body blood volume without fluid resuscitation. Mean blood pressure, heart rate and arterial blood gas components were recorded up to 5 hours after the bleeding. The levels of TNF-alpha, IL-1beta and lactic dehydrogenase (LDH)-3 isozyme were measured in the serum of pulmonary venous blood. The lung tissue was excised for the assay of mRNA and for histopathological study. RESULTS: The expressions of mRNA for TNF-alpha and IL-1beta in the lung tissue and the concentrations of both cytokines in pulmonary serum increased after a hemorrhage. Inflammation-related injuries and function deterioration were observed in the lung following hemorrhagic shock. These hemorrhagic changes were inhibited by pretreatment with FR167653. CONCLUSIONS: TNF-alpha and IL-1beta play a key role in the development of inflammation-related lung dysfunction following hemorrhagic shock. Our model should be useful to explain the pathogenesis of lung dysfunction following hemorrhagic shock.     

Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection.

OBJECTIVE: To evaluate concentrations of interleukin (IL)-6, IL-8, lactoferrin (LF), and alpha defencine (alpha-DF) in the cervical mucus of pregnant women and analyze their relation to cervicitis and bacterial vaginosis (BV). METHODS: Cervical mucus samples were obtained from August 2003 through May 2004 from 157 women who were between the 6th and 36th week of an uncomplicated singleton pregnancy. All women were delivered at term, 69 without BV or cervicitis, 9 with BV, and 79 with cervicitis. RESULTS: Interleukin 8, LF, and mu-DF concentrations were higher in women with cervicitis (0.81 +/- 0.36 pg/mL, 14.8+/-12.3 microg/mL, and 0.60 +/- 0.49 microg/mL) than in women without BV or cervicitis (0.35 +/- 0.34 pg/mL, 8.0 +/- 11.0 microg/mL, and 0.15 +/- 0.12 microg/mL). Interleukin 6 concentration was higher in women with BV (0.26 +/- 0.32 pg/mL) than in women without BV or cervicitis (0.09 +/- 0.15 pg/mL) or in women with cervicitis (0.12 +/- 0.18 pg/mL). CONCLUSIONS: Higher levels of inflammatory cytokines in the cervical mucus of pregnant women may lead to early detection of lower genital tract infection.