Effect of VA-045, a novel apovincaminic acid derivative,on closed head injury-induced neurological dysfunction in aged rats

Abstract

Objective: The strength–duration time constant (SDTC) is a measure of axonal excitability and it can provide information about Na⁺ channel function. In this study, we sought to examine the changes in the SDTCs of motor and sensory fibers of the median nerve in patients taking colchicine, which affects axoplasmic flow and may result in axonal neuropathy.

Methods and results: The SDTCs of motor and sensory fibers of 29 patients who had been taking colchicine were measured following stimulation of the right median nerve at the wrist. The results were compared with ten healthy age-matched subjects. No significant differences were found between the groups.

Conclusions: The lack of any effect on the SDTC by colchicine might have been due to the fact that axonal degeneration caused by colchicine affects the Na⁺–K⁺ ATP pump or that it affects internodal channels other than nodal channels.     

Variations in lithium target thickness and proton energy stability for the near-threshold 7Li(p,n)7Be accelerator-based BNCT

The usable range of thickness for the solid lithium target in the accelerator-based neutron production for BNCT via the near-threshold (7)Li(p,n)(7)Be reaction was investigated. While the feasibility of using a (7)Li-target with thickness equal to that which is required to slow down a mono-energetic 1.900 MeV incident proton to the 1.881 MeV threshold of the (7)Li(p,n)(7)Be reaction (i.e., t(min) = 2.33 microm) has already been demonstrated, dosimetric properties of neutron fields from targets greater than t(min) were assessed as thicker targets would last longer and offer more stable neutron production. Additionally, the characteristics of neutron fields generated by (7)Li(p,n)(7)Be for Gaussian incident protons with mean energy of 1.900 MeV were evaluated at a (7)Li-target thickness t(min). The main evaluation index applied in this study was the treatable protocol depth (TPD) which corresponds to the depth in an irradiated medium that satisfies the requirements of the adapted dose protocol. A maximum TPD (TPD(max)) was obtained for each irradiation condition from the relationship between the TPD and the thickness of boron dose enhancer (BDE) used. For a mono-energetic 1.900 MeV proton beam, the deepest TPD(max) of 3.88 cm was attained at the (7)Li-target thickness of t(min) and a polyethylene BDE of 1.10 cm. When the intended TPD for a BNCT clinical treatment is shallower than the deepest TPD(max), the usable (7)Li-target thickness would be between t(min) and an upper limit t(upper) whose value depends on the BDE thickness used. In terms of the effect of stability of the incident proton energy, Gaussian incident proton energies stable to within +/-10 keV of 1.900 MeV were found to be feasible for the neutron production via the near-threshold (7)Li(p,n)(7)Be reaction for BNCT provided that a suitable BDE is used.     

Effects of residual coronary stenosis on myocardial salvage after reperfusion in dogs

In order to study the effects of residual stenosis on myocardial salvage, we created 99% coronary stenosis with or without contrast washout delay at reperfusion in six groups of dogs. In Group A (n = 8), the artery was occluded for 1h before being fully reperfused. In Group B (n = 9), the artery was occluded for 1h, then subjected to 6h of 99% stenosis without contrast washout delay. In Group C (n = 8), the artery was occluded for 1h, followed by 1 week of 99% stenosis without contrast washout delay. In Group D (n = 10), again the artery was occluded for 1h, then subjected to 6h of 99% stenosis with contrast washout delay. In Group E (n = 8), the artery was occluded for 7h, then fully reperfused for 1 week. Finally, in Group F (n = 8), the occlusion lasted for a full week. All dogs were sacrificed 1 week after occlusion. In Group A, myocardial creatine phosphokinase activity (CK) in the inner layer was 43.8 +/- 12.5% that of non-infarcted myocardium. Myocardial CK in Group B (46.5 +/- 7.4%) was little different but in Group C it dropped to 26.6 +/- 8.4%, suggesting that 99% residual stenosis is not deleterious if it is continued for 6h or less but that it will result in considerable depletion of myocardial CK, it is is sustained for 1 week. In Group D, myocardial CK dropped markedly to 11.3 +/- 3.7%, little different from that for either Group E (13.3 +/- 2.6%) or Group F (9.3 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis

The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2–4 weeks. The dose is then tapered by 5 mg every 1–2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.     

Induction of β-Defensin Expression by Porphyromonas gingivalis-Infected Human Gingival Graft Transplanted in nu/nu Mouse Subdermis

It is important to understand the onset of periodontal disease in terms of bacterial infection and host factors. Host-bacteria interactions can be elicited in human cultured cells and animal models, but these models provide only limited biological information about human host reactions against bacterial attacks. Development of an in vivo model using human gingival tissue is needed. We established an in vivo model using nu/nu mice and evaluated host defense following bacterial infection in human gingiva. Human gingival samples were collected from periodontitis patients and transplanted in nu/nu mouse subdermis. After 2 weeks, human characteristics were confirmed by positive immunohistochemical reactions for human-specific markers. We used this model to investigate human β-defensin-2 (hBD-2), an antimicrobial peptide that contributes to initial defense against bacterial invasion. Using real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry, we investigated whether hBD-2 expression was induced in human gingiva as a response to Porphyromonas gingivalis as a periodontal pathogen. Two hours after infection with bacteria, we detected increased expression of hBD-2 mRNA, which was localized in the epithelium of human gingiva. Using our in vivo model, we concluded that increased hBD-2 may play an important role in early defense from bacterial infection in human gingival epithelium.