Measurement of nuclear reaction cross sections by using Cherenkov radiation toward high-precision proton therapy.

Monitoring the in vivo dose distribution in proton therapy is desirable for the accurate irradiation of a tumor. Although positron emission tomography (PET) is widely used for confirmation, the obtained distribution of positron emitters produced by the protons does not trace the dose distribution due to the different physical processes. To estimate the accurate dose from the PET image, the cross sections of nuclear reactions that produce positron emitters are important yet far from being sufficient. In this study, we measured the cross sections of 16O(p,x)15O, 16O(p,x)13N, and 16O(p,x)11C with a wide-energy range (approximately 5-70 MeV) by observing the temporal evolution of the Cherenkov radiation emitted from positrons generated via ß+ decay along the proton path. Furthermore, we implemented the new cross sectional data into a conventional Monte Carlo (MC) simulation, so that a direct comparison was possible with the PET measurement. We confirmed that our MC results showed good agreement with the experimental data, both in terms of the spatial distributions and temporal evolutions. Although this is the first attempt at using the Cherenkov radiation in the measurements of nuclear cross sections, the obtained results suggest the method is convenient and widely applicable for high precision proton therapy.

CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion.

Glucagon-like peptide-1 (GLP-1) promotes insulin release; however, the relationship between the GLP-1 signal and chronic pancreatitis is not well understood. Here we focus on chemokine (C-C motif) ligand 2 (CCL2) and its receptor (CCR2) axis, which regulates various immune cells, including macrophages, to clarify the mechanism of GLP-1-mediated insulin secretion in chronic pancreatitis in mice. One and multiple series of repetitive cerulein administrations were used to induce acute and chronic cerulein pancreatitis, respectively. Acute cerulein-administered CCR2-knockout (KO) mice showed suppressed infiltration of CD11b(+)Gr-1(low) macrophages and pancreatic inflammation and significantly upregulated insulin secretion compared with paired wild-type (WT) mice. However, chronic cerulein-administered CCR2-KO mice showed significantly increased infiltration of CD11b(+)/Gr-1(-) and CD11b(+)/Gr-1(high) cells, but not CD11b(+)/Gr-1(low) cells, in pancreas with severe inflammation and significantly decreased insulin secretion compared with their WT counterparts. Furthermore, although serum GLP-1 levels in chronic cerulein-administered WT and CCR2-KO mice were comparably upregulated after cerulein administrations, GLP-1 receptor levels in pancreases of chronic cerulein-administered CCR2-KO mice were significantly lower than in paired WT mice. Nevertheless, a significantly higher hyperglycemia level in chronic cerulein-administered CCR2-KO mice was markedly restored by treatment with a GLP-1 analog to a level comparable to the paired WT mice. Collectively, the CCR2/CCL2 axis-mediated CD11b(+)-cell migration to the pancreas is critically involved in chronic pancreatitis-mediated hyperglycemia through the modulation of GLP-1 receptor expression and insulin secretion.

Marked improvement of fertility of cryopreserved C57BL/6J mouse sperm by depletion of Ca2+ in medium.

Cryopreservation of mouse sperm is useful for maintaining various strains. However, fertility generally decreases after freezing. In particular, the fertility of cryopreserved C57BL/6J sperm is very low. To improve the fertility of frozen sperm, we examined the efficiencies of various media used for sperm preincubation (SP) and in vitro fertilization (IVF) in frozen C57BL/6J sperm. In this study, SP medium was examined for efficiency of fertility with respect to content, especially calcium (Ca(2+)), phosphate (PO(4)(3-)) and lactate. In all media containing no Ca(2+), including medium lacking Ca(2+), lacking Ca(2+) and PO(4)(3-), lacking Ca(2+) and lactate and lacking Ca(2+), PO(4)(3-) and lactate, high IVF rates were obtained (79, 69, 76 and 71%, respectively). On the other hand, the rates for media containing Ca(2+) were significantly lower (30-38%, P<0.05). After transfer, 41-50% of newborns were obtained in all media containing no Ca(2+). In conclusion, preincubation of thawed sperm in medium containing no Ca(2+) markedly improved the fertility of cryopreserved C57BL/6J sperm. These results indicate that the present method of IVF using medium with no Ca(2+) is practical for use in cryopreserved C57BL/6J sperm.

Cryoprotective effects of various saccharides on cryopreserved mouse sperm from various strains.

Aim: Cryopreservation of mouse sperm commonly uses raffinose, which is a trisaccharide, plus 3% skim milk. Because of the present lack of knowledge of the effectiveness of any other saccharides, we examined the cryoprotective effects of various saccharides on the viability of mouse sperm from various strains to determine which saccharides are the best cryoprotectants for mouse sperm. Methods: Sperm from the caudae epididymides of mature C57BL/6J mice were frozen with monosaccharides (fructose, glucose, rhamnose, xylose), disaccharides (lactose, maltose, sucrose, trehalose) or trisaccharides (melezitose, raffinose) in a range of concentrations (4-33%). After thawing, the optimal concentration was determined to be the concentration in which there was the highest proportion of motile sperm. In addition, sperm of inbred and hybrid mice were frozen with the saccharides at the optimal concentrations and used for in vitro fertilization. Results: The optimal concentration was 12% for the disaccharides and 18% for the trisaccharides. The fertility of all strains, except C57BL/6J, showed the best cryoprotective effects with maltose, melezitose and raffinose when compared with fresh sperm. Conclusion: Maltose, melezitose and raffinose have the best effects when used as a protectant for cryopreservation of mouse sperm. (Reprod Med Biol 2007; 6: 229-233).