Detection of non-palpable breast cancer in asymptomatic women by using unenhanced diffusion-weighted and T2-weighted MR imaging: comparison with mammography and dynamic contrast-enhanced MR imaging

Objective

To compare the detectability of non-palpable breast cancer in asymptomatic women by using mammography (MMG), dynamic contrast-enhanced MR imaging (DCE-MRI) and unenhanced MR imaging with combined diffusion-weighted and T2-weighted images (DWI?+?T2WI).

Methods

Forty-two lesions in 42 patients with non-palpable breast cancer in asymptomatic women were enrolled. For the reading test, we prepared a control including 13 normal and 8 benign cases. Each imaging set included biplane MMG, DCE-MRI and DWI?+?T2WI. Five readers were asked to rate the images on a scale of 0 to 100 for the likelihood of the presence of cancer and the BI-RADS category. Confidence level results were used to construct receiver operating characteristic analysis. Sensitivity and specificity were calculated for each technique.

Results

DWI?+?T2WI showed higher observer performances (area under the curve, AUC, 0.73) and sensitivity (50%) for the detection of non-palpable breast cancer than MMG alone (AUC 0.64; sensitivity 40%) but lower than those of DCE-MRI (AUC 0.93; sensitivity 86%). A combination of MMG and DWI?+?T2WI exhibited higher sensitivity (69%) compared with that of MMG alone (40%).

Conclusion

DWI?+?T2WI could be useful in screening breast cancer for patients who cannot receive contrast medium and could be used as a new screening technique for breast cancer.     

Acetaminophen enhances pruritus in a mouse model of contact dermatitis induced by suboptimal concentration of hapten

Acetaminophen (APAP) is one of the most commonly used drugs worldwide to reduce fever, particularly in children. It is generally considered to be a safe drug. However, a number of studies have shown that regular use of APAP increases the risk of developing allergic diseases. Nonetheless, no animal models have been used to investigate these findings. Therefore, we aimed to create an animal model of APAP-induced pruritus in mice. APAP (0.25% and 0.5%) was administered via drinking water daily from infancy, and a suboptimal concentration of 2,4,6-trinitrochlorobenzene (TNCB) was applied repeatedly to each ear three times a week for 7 weeks to evoke chronic allergic contact dermatitis. Neither 0.25% nor 0.5% APAP was overtly hepatotoxic after 73 days of daily administration. Repeated challenge with TNCB evoked increase in the number of scratching bouts compared to day 1. This increase in the number of scratching bouts was significant in 0.25% and 0.5% APAP groups but not in the group treated with TNCB alone. Daily administration of 0.5% APAP significantly increased in the number of scratching bouts compared to TNCB alone on day 29. This animal model will be useful for investigating the mechanism underlying the increased risk of development of eczema caused by regular APAP use and for examining safer and more effective therapy with APAP.     

Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.     

Acetylcholinesterase inhibitors attenuate angiogenesis

Donepezil {(RS)-2-[(1-benzyl-4-piperidyl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one} is a reversible acetylcholinesterase inhibitor and used for treatment of patients with AD (Alzheimer's disease). Recent studies showed that treatment with donepezil reduced production of inflammatory cytokines in PBMCs (peripheral blood mononuclear cells). It was also reported that muscle-derived inflammatory cytokines play a critical role in neovascularization in a hindlimb ischaemia model. We sought to determine whether donepezil affects angiogenesis. A hindlimb ischaemia model was created by unilateral femoral artery ligation. Blood flow recovery examined by laser Doppler perfusion imaging and capillary density by immunohistochemical staining of CD31-positive cells in the ischaemic hindlimb were significantly decreased in donepezil- and physostigmine-treated mice compared with control mice after 2 weeks. Donepezil reduced expression of IL (interleukin)-1β and VEGF (vascular endothelial growth factor) in the ischaemic hindlimb. Intramuscular injections of IL-1β to the ischaemic hindlimb reversed the donepezil-induced VEGF down-regulation and the anti-angiogenic effect. Hypoxia induced IL-1β expression in C2C12 myoblast cells, which was inhibited by pre-incubation with ACh (acetylcholine) or LY294002, a PI3K (phosphoinositide 3-kinase) inhibitor. Donepezil inhibited phosphorylation of Akt [also known as PKB (protein kinase B)], a downstream kinase of PI3K, in the ischaemic hindlimb. These findings suggest that cholinergic stimulation by acetylcholinesterase inhibitors suppresses angiogenesis through inhibition of PI3K-mediated IL-1β induction, which is followed by reduction of VEGF expression. Acetylcholinesterase inhibitor may be a novel anti-angiogenic therapy.     

Severe osteomalacia caused by short bowel syndrome in a patient on long-term hemodialysis after parathyroidectomy

In January 2009, a 70-year-old Japanese woman on long-term dialysis was admitted to our hospital for evaluation of a painful left leg. Maintenance dialysis was started in 1982, and parathyroidectomy was performed for secondary hyperparathyroidism in 2004. Most of her small intestine was resected because of superior mesenteric artery thrombosis in 2006, and the remaining small bowel only extended 50 cm distal to the ligament of Treitz. Parenteral nutrition was started after bowel resection. Fracture of her left leg occurred suddenly without any precipitating factors in January 2009, and iliac bone biopsy revealed severe osteomalacia with an increase of total osteoid volume (57.6%) (>15%) and no fibrous tissue (0%) (<0.5%). Although phosphorus and active vitamin D were administered intravenously to correct her hypophosphatemia and vitamin D deficiency, significant improvement was not achieved. This case indicates that when a patient on long-term dialysis with parathyroidectomy also suffers from short bowel syndrome, osteomalacia may become very severe. Lack of healing of the fracture, persistence of pain, and subsequent fracture even after vigorous treatment for low serum phosphate and calcitriol levels implied that these medications were not necessarily sufficient for this patient.     

A new loop-mediated isothermal amplification method for rapid, simple, and sensitive detection of Leptospira spp. in urine

We developed a new loop-mediated isothermal amplification (LAMP) method to detect rrs, a 16S rRNA gene of pathogenic Leptospira spp. in urine. The method enables detection of two leptospiral cells per reaction mixture following boiling of urine specimens. The sensitivity of this method is higher than that of culture or of flaB nested PCR.     

Thrombosis from a prothrombin mutation conveying antithrombin resistance

We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was substantially impaired. A thrombin-generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis.