A Method for the Automatic Exposure Control in Pediatric Abdominal CT: Application to the Standard Deviation Value and Tube Current Methods by Using Patient's Age and Body Size.

We aimed to apply the pediatric abdominal CT protocol of Donnelly et al. in the United States to the pediatric abdominal CT-AEC. Examining CT images of 100 children, we found that the sectional area of the hepatic portal region (y) was strongly correlated with the body weight (x) as follows: y=7.14x + 84.39 (correlation coefficient=0.9574). We scanned an elliptical cone phantom that simulates the human body using a pediatric abdominal CT scanning method of Donnelly et al. in, and measured SD values. We further scanned the same phantom under the settings for adult CT-AEC scan and obtained the relationship between the sectional areas (y) and the SD values. Using these results, we obtained the following preset noise factors for CT-AEC at each body weight range: 6.90 at 4.5-8.9 kg, 8.40 at 9.0-17.9 kg, 8.68 at 18.0-26.9 kg, 9.89 at 27.0-35.9 kg, 12.22 at 36.0-45.0 kg, 13.52 at 45.1-70.0 kg, 15.29 at more than 70 kg. From the relation between age, weight and the distance of liver and tuber ischiadicum of 500 children, we obtained the CTDIvol values and DLP values under the scanning protocol of Donnelly et al. Almost all of DRL from these values turned out to be smaller than the DRL data of IAEA and various countries. Thus, by setting the maximum current values of CT-AEC to be the Donnelly et al.'s age-wise current values, and using our weight-wise noise factors, we think we can perform pediatric abdominal CT-AEC scans that are consistent with the same radiation safety and the image quality as those proposed by Donnelly et al.

Factors Contributing to the Clinical Effectiveness of the DPP-4 Inhibitor Sitagliptin in Patients With Type 2 Diabetes.

PURPOSE: Treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors may have responders or nonresponders. However, agreement on the effects of patient background and/or contributory factors that have a negative effect on the efficacy of DPP-4 inhibitors is lacking. The aim of the present study was to investigate the effect of resistance factors on the clinical efficacy of sitagliptin (SITA) for patients with type 2 diabetes. METHODS: We performed a retrospective study based on the medical records of patients who were treated with SITA alone (SITA-A; n = 16), a combination of a sulfonylurea (SU) without a change in dose and add-on SITA (SU + SITA; n = 29), SITA alone after the discontinuation of premedication with antidiabetic agents (SITA-AD; n = 18), or a combination of an SU with a dose reduction and SITA (L-SU + SITA; n = 17). Multivariate logistic regression analysis was employed to estimate the influence of resistance factors on hemoglobin (Hb) A1c lowering by SITA treatment for 3 months. FINDINGS: The HbA1c levels were significantly lower after 3-month treatment with SITA-A (6.3% [0.2%]), SU + SITA (7.1% [0.2%]), and L-SU + SITA (6.6% [0.2%]), but not with SITA-AD (6.3% [0.2%]), than baseline levels before treatment. Multivariate logistic regression analysis established that a decreased efficacy of SITA was markedly related to baseline HbA1c levels of ≥7.5% and dyslipidemia. IMPLICATIONS: These results suggest that checking for the presence or absence of resistance factors, including elevated HbA1c levels and dyslipidemia, may contribute to the appropriate usage of SITA.

[Effects of practical training to increase motivation for learning and related factors].

Under the six-year pharmaceutical education system that was initiated in April 2006, students who had completed the course in March 2012 became the first graduates. The six-year system encourages students to develop a well-rounded personality, a deep sense of ethics, knowledge required for health care professionals, abilities to identify and solve problems, and practical skills required in clinical settings, as well as basic knowledge and skills. Under the new education system based on the "pharmaceutical education model core curriculums" and "practical training model core curriculums", general pharmaceutical education is implemented in each college, and five-month practical training is conducted in clinical settings. Clinical tasks experienced by students for the first time are expected to significantly influence their motivation to learn and future prospects. In the present survey research, students who had completed practical training evaluated the training program, and correspondence and logistic regression analyses of the results were conducted to examine the future effects and influences of the training on the students. The results suggest that the students viewed the practical training program positively. In addition, clinical experience during the training sessions not only influenced their decisions on future careers, but also significantly increased their motivation to learn. Furthermore, their motivation for learning was increased most by the enthusiasm of pharmacists who advised them in clinical settings, rather than the training program itself. To improve pharmaceutical clinical learning, it is important to develop teaching and working environments for pharmacists in charge of advising students in clinical training.

[Estimating elapsed time of brain hemorrhage using computed tomography value-based parameters].

We measured the time-dependent change of computed tomography (CT) values for a blood sample in a syringe during 20 days expecting that the (average, maximum) CT values may be used to estimate the elapsed time after hemorrhage. The average CT value (CT(ave)) rapidly increased for the first 50 min. The maximum CT value (CT(max)) increased step by step to take the largest value (82.4 HU) one day later, and subsequently the CT(max) decreased slowly to become 72.0 HU 20 days later. We conclude that the rapid increase of the CT(ave) at the beginning is due to the fibrin generation, the increase of the CT(max) is a result of the formation of the fibrin net, and the subsequent decrease of CT(max) is caused by fibrinolysis. Tentative experimental formula for the time-dependent CT(max) change at each increasing stage and decreasing stage are given to estimate the elapsed time after hemorrhage.

Local anesthetic cream prepared from lidocaine-tetracaine eutectic mixture.

Local anesthetic creams for the clinical treatment of conditions such as postherpetic neuralgia were prepared as an in-house formulation from the eutectic mixture of lidocaine-tetracaine (LT cream) using two eutectic mixtures of local anesthetic (EMLA) type bases. The LT formulation was compared with a lidocaine-prilocaine (LP cream) eutectic mixture formulated using the same base as EMLA. The chemical stability of lidocaine was examined in advance and was found to be stable for more than 3 months either in LT cream or in LP cream. The release rate of lidocaine from the formulated creams was examined using a cellulose ester membrane. The release rate of lidocaine from LT cream was similar to that from LP cream. The release rate of tetracaine was slightly slower than that of lidocaine in LT cream reflecting the larger molecular size of tetracaine. The penetration rate was examined in vitro using a Yucatan micropig skin. The penetration rate of lidocaine was similar between LT and LP creams. Infiltration anesthesia action examined in guinea pigs indicated that the difference between the two creams was statistically insignificant. The present study suggests the equivalence of the LT and LP creams as a local anesthetic and the potential of LT cream for clinical use either in the easy formulation or in the low-cost formulation.

Histamine-induced vasodilation and vasoconstriction in the mesenteric resistance artery of the rat.

The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, perfusion of histamine (1 nM-100 microM) produced a concentration-dependent vasodilation. Histamine-induced vasodilation was attenuated by L-NAME (nitric oxide (NO) synthase inhibitor, 100 microM) and olopatadine (histamine H(1) receptor antagonist, 1 microM) but not by lafutidine (histamine H(2) receptor antagonist, 1 microM). Cold-storage denervation (4 degrees C for 72 h) of the preparation with intact endothelium attenuated the histamine-induced vasodilation. In preparations without endothelium, histamine at low concentrations (1-100 nM) produced only a small and rapid vasodilation, whereas histamine at concentrations higher than 1 muM produced triphasic vascular responses: initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. Lafutidine abolished only the histamine-induced initial vasodilation. Olopatadine abolished the histamine-induced second vasoconstriction and third vasodilation. Cold-storage denervation of the denuded preparation abolished the histamine-induced second vasoconstriction and third vasodilation. These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H(1) receptors and endothelium-independent vasodilation via smooth muscle histamine H(2) receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H(1) receptors and perivascular nerves.

Neuronal nitric-oxide synthase inhibition facilitates adrenergic neurotransmission in rat mesenteric resistance arteries.

The effects of nonselective nitric-oxide synthase (NOS) inhibitors [N-omega-nitro-L-arginine methyl ester (L-NAME) and N-omega-nitro-L-arginine (L-NNA)] and specific neuronal NOS (nNOS) inhibitor [vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO)] on adrenergic nerve-mediated vasoconstriction were studied in rat perfused mesenteric vascular beds without endothelium. Perfusion of L-NAME, L-NNA, or l-VNIO markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS; 2-8 Hz) without affecting vasoconstriction induced by exogenously injected norepinephrine (NE). Addition of L-arginine, a precursor for the synthesis of nitric oxide (NO), reversed the augmentation of the PNS response by l-NAME. The PNS (8 Hz)-evoked NE release in the perfusate was increased by L-NAME perfusion. In preparations treated with capsaicin [a depleter of calcitonin gene-related peptide (CGRP)-containing nerves], L-NAME did not augment vasoconstrictor responses to PNS or NE injection. Combined perfusion of CGRP(8-37) (a CGRP receptor antagonist) and L-NAME induced additive augmentation of the vasoconstrictor response to PNS but did not affect the response to NE injection. In preparations with active tone produced by methoxamine and in the presence of guanethidine, L-NAME perfusion did not affect the vasodilator response induced by PNS. Immunostaining of the mesenteric artery showed the presence of nNOS-like immunopositive nerve fibers, which were absent in arteries pretreated with capsaicin. These findings suggest that NO, which is released from perivascular capsaicin-sensitive nerves, presynaptically inhibits neurogenic NE release to modulate adrenergic neurotransmission.

Effect of adrenomedullin on adrenergic vasoconstriction in mesenteric resistance arteries of the rat.

Adrenomedullin (AM) is a hypotensive peptide that belongs to a family of peptides structurally related to calcitonin gene-related peptide (CGRP). The present study examined the effect of AM on adrenergic nerve-mediated vasoconstriction in rat perfused mesenteric vascular beds without endothelium. Perfusion of AM at 0.1 nM but not 10 nM increased vasoconstrictor responses to periarterial nerve stimulation (PNS) (1-4 Hz), while AM at 10 nM significantly attenuated vasoconstriction induced by bolus injection of norepinephrine (NE). In preparations treated with capsaicin (a CGRP depletor), pressor responses to both PNS and NE injection were markedly attenuated by AM. Perfusion of CGRP(8-37) (a CGRP-receptor antagonist) significantly potentiated the PNS- but not the NE-induced vasoconstriction. Combined perfusion of CGRP(8-37) and AM had no effect on the PNS-induced response and antagonized the inhibitory effect of AM on the NE-induced response. AM(2-52) (an AM-receptor antagonist) did not influence the effect of AM. These findings suggest that AM facilitates adrenergic vasoconstriction by inhibiting neurotransmission of CGRP-containing nerves, which counteract adrenergic nerve-mediated vasoconstriction.

Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats.

The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. The density of immunocytochemically stained nerve fibers in the mesenteric artery was quantified by computer-assisted image processing. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fivers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar Kyoto rats (WKY). The density of NPY-LI-containing sympathetic nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan) or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured by tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. However, the density after hydralazine treatment was similar to the level in non-treated SHR. The density of NPY-LI-containing nerve fibers was not increased by any of the drug treatments. These results suggest that long-term inhibition of the renin-angiotensin system in SHR prevents remodeling of CGRPergic nerve fibers and prevents the reduction of CGRPergic nerve function.

Adrenomedullin release in the rat mesenteric resistance artery.

Adrenomedullin (AM) is a potent vasodilator peptide whose major source is the vascular wall. In the present study, the mechanism of release of AM was investigated in the rat mesenteric resistance artery. The isolated mesenteric vascular bed was perfused with Krebs solution at a constant flow rate (5 ml/min) and AM in the perfusate was measured by a highly sensitive enzyme immunoassay (Immunoenzymometric assay; IEMA) method. In preparations without endothelium, spontaneous release of AM was detected in the perfusate (68.7+/-5.8 fmol/ml, n=45). Periarterial nerve stimulation (PNS, 4 and 8 Hz) caused 11.4+/-3.9% (4 Hz) and 9.1+/-3.5% (8 Hz) decreases in the spontaneous release of AM. Removal of Ca2+ from the medium did not affect the spontaneous AM release, but abolished the PNS-induced inhibition of spontaneous AM release. Perfusion of 10nM calcitonin gene-related peptide (CGRP) or 0.1 microM capsaicin (inducer of CGRP release) inhibited significantly the spontaneous AM release. PNS (8 Hz)-induced inhibition of spontaneous AM release was antagonized by CGRP(8-37) (CGRP receptor antagonist). These results suggest that AM is mainly released from vascular smooth muscle cells of the rat mesenteric artery and endogenous or exogenous CGRP inhibits AM release.

Vanilloid receptors mediate adrenergic nerve- and CGRP-containing nerve-dependent vasodilation induced by nicotine in rat mesenteric resistance arteries.

Previous studies showed that nicotine induces adrenergic nerve-dependent vasodilation that is mediated by endogenous calcitonin gene-related peptide (CGRP) released from CGRP-containing (CGRPergic) nerves. The mechanisms underlying the nicotine-induced vasodilation were further studied. Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine, and the perfusion pressure was measured with a pressure transducer. Perfusion of nicotine (1-100 microm) for 1 min caused concentration-dependent vasodilation. Capsazepine (vanilloid receptor-1 antagonist; 1-10 microm) and ruthenium red (inhibitor of vanilloid response; 1-30 microm) concentration-dependently inhibited the nicotine-induced vasodilation without affecting the vasodilator response to exogenous CGRP. Nicotine-induced vasodilation was not inhibited by treatment with 3,4-dihydroxyphenylalanine (DOPA) receptor antagonist (l-DOPA cyclohexyl ester; 0.001-10 microm), dopamine D1 receptor-selective antagonist (SCH23390; 1-10 microm), dopamine D2 receptor antagonist (haloperidol; 0.1-0.5 microm), ATP P2x receptor-desensitizing agonist (alpha,beta-methylene ATP; 1-10 microm), adenosine A2 receptor antagonist (8(p-sulfophenyl)theophylline; 10-50 microm) or neuropeptide Y (NPY)-Y1 receptor antagonist (BIBP3226; 0.1-0.5 microm). Immunohistochemical staining of the mesenteric artery showed dense innervation of CGRP- and vanilloid receptor-1-positive nerves, with both immunostainings appearing in the same neuron. The mesenteric artery was also densely innervated by NPY-positive nerves. Double immunostainings showed that both NPY and CGRP immunoreactivities appeared in the same neuron of the artery. These results suggest that nicotine acts on presynaptic nicotinic receptors to release adrenergic neurotransmitter(s) or related substance(s), which then stimulate vanilloid receptor-1 on CGRPergic nerves, resulting in CGRP release and vasodilation.

The GTS1 gene product facilitates the self-organization of the energy metabolism oscillation in the continuous culture of the yeast Saccharomyces cerevisiae.

To study the role of the GTS1 gene in the energy metabolism oscillation in continuous cultures of yeast from the physical aspect, time-series data of dissolved oxygen oscillations were analyzed by transforming them into power spectra and by creating two-dimensional trajectories using time delay embedding technique. We found that the wild-type cells organized themselves into a stable limit cycle oscillation and that the GTS1-deleted mutant, gts1Delta, usually showed transient oscillations whose power spectra resembled those of 1/f noise. Thus, we suggested that GTS1 plays an important role in the self-organization of the energy metabolism oscillation.