MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn²⁺ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn²⁺ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn²⁺ ions, as the addition of Ca‐DO2A to a solution of MnCl₂ causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn²⁺ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T₁‐weighted images is taken as evidence of the sequestration of extracellular Mn²⁺ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T₁ decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Successful choledochojejunostomy for choledochal stricture with preservation of the collateral parabiliary venous system following iatrogenic portal occlusion

We surgically treated a patient with biliary stricture and portal vein occlusion, after operation for gastric cancer with lymphadenectomy along the hepatoduodenal ligament, that had led to choledochal stone formation and a dilatated parabiliary venous system. A 57-year-old man without hepatic dysfunction exhibited hepatic duct dilatation with choledochal stone on ultrasonography and percutaneous transhepatic cholangiography, respectively. Pharmacoportography revealed occlusion of the portal vein and dilatation of the parabiliary venous system. Of various preoperative imaging studies used, enhanced computed tomography was most useful for delineating the surgical anatomy of the hepatoduodenal ligament. Complete preservation of the dilatated vessels, which functioned as the main portal collateral pathway, resulted in a successful choledocho-jejunostomy, with an uneventful postoperative course.     

Clinical effect of LM-001, prostaglandin synthetic inhibitor, on pain from urinary tract stone and vesical urgency after operation of the bladder or prostate

Clinical effect of LM-001, a prostaglandin synthetic inhibitor developed from a drug delivery system, was evaluated in 54 patients with pain from urinary tract stones (stone pain) and 32 with vesical urgency after an operation on bladder or prostate. LM-001, felbinac ethyl incorporated in lipid microsphere, wes intravenously administered at the onset of stone pain or vesical urgency. Of 54 with stones and 32 with urgency, 53 and 29 were eligible for response, respectively. The symptoms improved or disappeared in some cases just after the administration and in the majority of patients within 15 minutes, in 49 of 53 patients with stone pain. Further, the effectiveness lasted over 24 hours in 26 of the 49 responding to this agent. On one hand, improvement or disappearance of vesical urgency was recognized in 25 of 29 patients, and the effectiveness was observed shortly after injection in 16 and lasted over 24 hours in 13 cases. Toxicities of this drug were investigated in 54 patients with stone pain and 32 with urinary urgency. Side effects consisted of pain at the injection site in 4, a slight fall of blood pressure in 1, slight visual disturbance in 1, body heat sensation in 1, leukocytosis in 3 and elevation of alkaline phosphatase in 1. These symptoms were transient and disappeared without use of any agent. LM-001 is concluded to be a useful drug for controlling stone pain and vesical urgency since an immediate effect, long durability and high response rates were obtained without severe side     

Differential Effects of Anesthetics on Mitochondrial KATP Channel Activity and Cardiomyocyte Protection

Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.

Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.

Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection.     

Long‐term efficacy of biologics in the treatment of psoriasis: what do we really know?

Psoriasis is a chronic inflammatory condition that often requires life-long treatment. Conventional therapies have not fully met the needs of psoriatic patients, because of limited efficacy, adverse effects with cumulative use, and patient inconvenience. In the past decade, biologic immunotherapies have become accepted treatments for psoriasis as a result of perceived efficacy and safety on the part of patients and practitioners. However, most data on these medications come from relatively limited short-term trials. In this review, we will focus on the available long-term data on the efficacy of the biologic agents. We will emphasize the strengths and weakness of the available data of the biologic agents that are Food and Drug Administration (FDA)-approved for the treatment of moderate to severe psoriasis (alefacept, efalizumab, * etanercept, infliximab, and adalimumab), with the inclusion of a newer agent currently under FDA evaluation (ustekinumab).     

Some new clinical applications of rhinomanometry

Clinical applications of active anterior rhinomanometry of the oscillation type had been carried out for the purposes other than the conventional uses of rhinomanometry. 1. Effect of acupuncture upon the nasal resistance to airflow: Among 8 acupuncture points which were recorded in Chinese traditional medical literatures as effective for improving nasal breathing, Ingxiang point had been proved to possess definite effect of lowering the nasal resistance to air-flow in patients with congestion of nasal mucosa, whereas in other acupuncture points this effect was not certain. 2. The severity of snoring before and after treatment could be determined objectively by the measurement of nasal resistance to air-flow and the breathing pattern of the patient.     

X-ray CT of Duchenne muscular dystrophy skeletal muscles--chronological study for five years]

To clarify when and how rapidly individual muscles are damaged in the course of Duchenne muscular dystrophy (DMD), we followed X-ray CT of whole body skeletal muscles from 29 cases of DMD patients (age ranging 3 to 23 years) for a period of 2 to 6 years. Each patient had 2 to 5 scans with an average of 3.3. We evaluated chronological changes of 23 muscles from the entire body using the muscle damage stage defined as follows. The stages were classified into the following 5 stages: stage 0; normal, 1; area of fatty replacement less than 10% of whole muscle area, 2; area of fatty replacement between 10 to 50%, 3; area of fatty replacement 50 to 90%, 4; almost complete fatty replacement. Each muscle had its own period of rapid degeneration starting at 5 to 10 years of age and, continuing 5 to 10 years. In some muscles such as gluteus maximus or quadriceps femoris, fatty replacement started at 5 years or earlier and progressed for five years, while other muscles such as splenius capitis, damage started much later, e.g. around 10 years of age and the progression was much slower. There was a variation of at least 5 years among individual patients in any muscle damage stage, reflecting the variability of clinical severity in each patient. On the basis of the above results we defined the whole body muscle damage index as a summation of the muscle damage stages of the following five muscles: gluteus maximus, quadriceps femoris, gracilis, medial head of gastrocnemius and splenius capitis.(ABSTRACT TRUNCATED AT 250 WORDS)