Development of a z-axis tilting technique using a chest phantom to reduce radiation exposure during computed tomography coronary angiography.

Japan has the highest estimated exposure frequency of diagnostic X-rays in the world. Furthermore, the volumetric computed tomography dose index (CTDIvol) and dose length product (DLP) of computed tomography coronary angiography are relatively high in Japanese diagnostic reference levels, and it is important to reduce both dose indices. This study proposed a new exposure reduction technique, the vanishing liver position (VLP), where the body is tilted to the right in the z-axis. The VLP advantages include reduction in the scanning range and overlap between the heart and the liver. Three different electrocardiogram protocols were employed, and changes in the tube current in the z-axis were measured during each protocol. Additionally, changes in the radiation exposure caused by z-axis tilting were evaluated. Our results indicate that this technique reduced CTDIvol and DLP by 6.2 and 8.9%, respectively, at most, indicating that this technique can reduce radiation exposure.

SIMPLE METHOD OF MEASURING SSDE FOR HEAD CT: FACILITATING PRE-CT SCAN DOSE CALCULATION USING SPECIALIZED HEAD SCAN BAND.

In this study, scaled scan band was developed to provide size-specific dose estimation (SSDE) values based on head circumference of patients undergoing computed tomography (CT) scans. The scan band was tested in 40 consecutive head CT examinations. The accuracy of the specialized scan band method was determined by comparing SSDEband with SSDE293,forehead, SSDEmean and SSDEcenter. SSDE293,forehead was used as the control value. The results of the linear fit of SSDEband, SSDEmean and SSDEcenter against SSDE293, forehead, were R2 = 0.958, R2 = 0.984 and R2 = 0.936, respectively. There was no significant difference between SSDEband, SSDEmean and SSDEcenter for SSDE293,forehead. Use of the proposed scan band method makes it possible to accurately determine the required radiation dose before a CT examination is performed.

DEVELOPMENT OF A SPECIALISED TAPE MEASURE TO ESTIMATE THE SIZE-SPECIFIC DOSE ESTIMATE.

The risk in computed tomography (CT) examinations is radiation exposure. We aimed to develop a specialised tape measure for determining the size-specific dose estimate (SSDE) for patients undergoing CT scans. The scanning parameters used were those of the abdominal protocol in our institute. With this method, the SSDE220 and standard deviations obtained from CT images for the liver, pelvic and lung areas, corresponded closely to the SSDEtape and standard deviations obtained using the tape measure. We thus devised a new idea that allows the estimation of the SSDE220 using a specialised tape measure before the CT examination, allowing for an informed explanation of the radiation dose to the patient. Although the tape measure developed in this study is specific to one particular CT instrument, the method could be adapted to a wide range of radiography applications.

Effect of table height displacement and patient center deviation on size-specific dose estimates calculated from computed tomography localizer radiographs.

The aim of this study is to evaluate the effect of table height displacement and patient center deviation along the [Formula: see text]-axis on size-specific dose estimate (SSDE) calculations based on computed tomography (CT) localizer radiographs in pediatric and adult abdominal CT examinations. CT localizer radiographs and CT axial images were acquired with table heights of - 5.0, - 2.5, 0.0 (center), 2.5, and 5.0 cm using two acrylic self-made phantoms filled with water. Water-equivalent diameters ([Formula: see text]) were calculated from the CT localizer radiographs and CT axial images. Relative errors of SSDEs from the CT localizer radiographs to SSDEs from the CT axial images were calculated to evaluate the effect of table height displacement. Furthermore, patient center deviations and indices of SSDE overestimation were measured from the clinical data of 110 abdominal CT examinations. The relative errors of SSDEs in phantoms equivalent to 1-year-old and 20-year-old Japanese reference persons ranged from - 2.45% (table height of 50 mm) to + 1.88% (- 50 mm) and from - 4.22% (50 mm) to + 3.79% (- 50 mm), respectively. The largest center deviation in all patients ranged from - 43.1 to 21.5 mm (median: - 14.4 mm). The indices of SSDE overestimation for all patients ranged from - 16.2 to 6.9 mm (median: - 2.2 mm). We found that the effects of table height displacement and patient center deviation along the [Formula: see text]-axis on SSDEs calculated from CT localizer radiographs in pediatric phantoms were smaller compared to adult phantoms. In order to correct these patient center deviations, it is necessary to apply an appropriate correction technique in each section along the [Formula: see text]-axis.

Analysis of Image Gently Abdominal CT Protocol With the Use of Body Phantom Adapted to the Japanese Size.

OBJECTIVE: The purpose of this study was to analyze in detail the quality of abdominal CT images obtained using three protocols reported by Image Gently in 2014 (hereafter referred to as Image Gently 2014), with the use of a handmade body phantom adapted to typical body sizes of the Japanese population. Moreover, we converted the findings of Image Gently 2014 to match Japanese body sizes and referred to our converted findings as Image Gently Japan. MATERIALS AND METHODS: We scanned each phantom in a mechanical isocenter in accordance with the Image Gently 2014 abdominal imaging protocol. We changed the tube current-exposure time product per rotation from 25 to 250 mAs. The bowtie filter was set with a minimum FOV for the phantom size. We then analyzed the volume CT dose index (CTDIvol)-measured CT number curve. We then used this CT number curve to calculate the CT number recommended by Image Gently Japan for each of the designated patient ages. RESULTS: The CTDIvol-measured CT number curve showed that, as the CTDIvol increased with each age, image noise decreased. When we assumed that the CTDIvol value for adults was 20 mGy, the measured CT number was 12.5 HU. We then multiplied each reduction coefficient by age (neonate and 1, 5, 10, and 15 years). The measured CT numbers for Image Gently Japan performed to attain limited dose reduction were 3.0, 3.9, 4.9, 6.0, and 9.0 HU, respectively, whereas those for Image Gently Japan performed to achieve moderate dose reduction were 3.3, 4.3, 5.3, 6.3, and 9.3 HU, respectively, and those for Image Gently Japan performed to attain aggressive dose reduction were 4.1, 5.1, 5.8, 6.8, and 9.5 HU, respectively. CONCLUSION: We analyzed the abdominal image quality demanded by Image Gently 2014, and we were able to adapt the results to the Japanese population and present them as our own Image Gently Japan recommendations. If the results of the present study become a foundation for scanning parameters for Japanese patients, we believe that they will eventually lead to a reduction in medical radiation exposure for this patient population.

Novel solid self-emulsifying drug delivery system of coenzyme Q10 with improved photochemical and pharmacokinetic behaviors.

The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 µm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10).

Inhalable sustained-release formulation of long-acting vasoactive intestinal peptide derivative alleviates acute airway inflammation.

The present study was undertaken to develop a respirable sustained-release powder (RP) formulation of long-acting VIP derivative, [Arg(15, 20, 21), Leu(17)]-VIP-GRR (IK312532), using PLGA nanospheres (NS) with the aim of improving the duration of action. NS formulation of IK312532 (IK312532/NS) was prepared by an emulsion solvent diffusion method in oil, and a mixture of the IK312532/NS and erythritol was jet-milled and mixed with lactose carrier to obtain the IK312532/NS-RP. Physicochemical properties were characterized focusing on appearance, particle size, and drug release, and in vivo pharmacological effects were assessed in antigen-sensitized rats. The IK312532/NS with a diameter of 140 nm showed a biphasic release pattern in distilled water with ca. 20% initial burst for 30 min and a sustained slow release up to ca. 55% for 24h. Laser diffraction analysis demonstrated that IK312532/NS-RP had fine dispersibility and suitable particle size for inhalation. In antigen-sensitized rats, insufflated IK312532/NS-RP (10 µg of IK312532/rat) could suppress increases of granulocyte recruitment and myeloperoxidase in pulmonary tissue for up to 24h after antigen challenge, although IK312532-RP at the same dose was less effective with limited duration of action. From these findings, newly prepared IK312532/NS-RP might be of clinical importance in improving duration of action and medication compliance for treatment of airway inflammatory diseases.

In vitro and in vivo characterization of new formulations of St. John's Wort extract with improved pharmacokinetics and anti-nociceptive effect.

The main purpose of the present study was to develop a novel formulation of St. John's Wort (SJW) extract with the aim of improving its pharmacokinetics and anti-nociceptive effect. Several formulations of SJW were prepared, including cyclodextrin inclusion (SJW-CD), solid dispersion (SJW-SD), dry-emulsion (SJW-DE), and nano-emulsion (SJW-NE). Physicochemical properties of SJW formulations were characterized with a focus on the morphology, dissolution behavior, colloidal properties, and dispersion stability in water. Although all the SJW formulations and SJW extract itself exhibited fine dissolution behavior in water, SJW extract and most formulations tended to cream, aggregate, or flocculate after dispersion in distilled water. In contrast, there were no significant changes in appearance and particle size of the SJW-NE for at least a few weeks, suggesting that SJW-NE was the most stable form as a carrier of SJW in the present study. After oral administration of the SJW-NE formulation (5.2 mg hyperforin/kg) in mice, higher hyperforin exposure in plasma (1188 ± 41 nM·h) and the brain (52.9 ± 1.6 pmol/g tissue·h) was observed with 2.8- and 1.3-fold increases of the area under the concentration curve from 0 to 6 hours (AUC(0-6)) compared to those of the SJW extract (417 ± 41 nM·h in plasma and 41.6 ± 1.5 pmol/g tissue·h in the brain). In the formalin test for scoring properties of the first and second phases of the pain response in mice, single oral administration of SJW-NE significantly reduced the nociceptive response compared with SJW extract. From these findings, the NE approach might be efficacious in improving the oral bioavailability and anti-nociceptive effect of SJW extract.

Inhalable sustained-release formulation of glucagon: in vitro amyloidogenic and inhalation properties, and in vivo absorption and bioactivity.

PURPOSE: The present study aimed to develop novel glucagon-loaded PLGA nanospheres without cytotoxic fibril formation for chronic glucagon replacement therapy. METHODS: Glucagon-loaded nanospheres (GLG/NS) were prepared by an emulsion solvent diffusion method in oil, and a respirable powder formulation (GLG/NS-RP) was prepared with a jet mill. Physicochemical and inhalation properties of GLG/NS-RP were characterized, and pharmacokinetic behavior and hyperglycemic effect of intratracheally instilled GLG/NS-RP were evaluated in rats. RESULTS: Although preparation of GLG/NS using glucagon solution at concentrations over 10 mg/mL led to significant formation of cytotoxic glucagon aggregates, glucagon solution at less than 5 mg/mL did not cause structural changes. Drug release behavior of GLG/NS showed a biphasic pattern with an initial burst and slow diffusion. Laser diffraction and cascade impactor analyses of GLG/NS-RP suggested high dispersion and deposition in the respiratory organs with a fine particle fraction of 20.5%. After the intratracheal administration of the GLG/NS-RP (200 µg glucagon/kg) in rats, glucagon was released in a sustained manner, leading to sustained hyperglycemic effects compared with those of normal glucagon powder. CONCLUSION: These data would suggest a therapeutic benefit of the newly developed GLG/NS-RP as an alternative to the injection form of glucagon currently used.

Development of PACAP38 analogue with improved stability: physicochemical and in vitro/in vivo pharmacological characterization.

Pituitary adenylate cyclase activating polypeptide 38 (PACAP38), one of the major peptide transmitters, has emerged as a promising drug candidate for the treatment of type 2 diabetes. In the present study, on the basis of previous structure-activity relationships, a new PACAP38 derivative, [R(15, 20, 21), L(17)]-PACAP38, was chemically synthesized with the aim of enhancing the therapeutic potential of PACAP38. The solution structure of the new derivative was almost identical to that of PACAP38 as evaluated by circular dichroic spectroscopy, and both PACAP38 and the new derivative stimulated adenylate cyclase in rat insulinoma RIN-m5F cells with EC(50) values of 4.6 and 5.5 nM, respectively. Stability studies revealed the gradual degradation of PACAPs in rat serum, although there appeared to be a 42% reduction in degradation kinetics for [R(15, 20, 21), L(17)]-PACAP38 compared with that of PACAP38. The novel derivative also exhibited more potent protective effects against streptozotocin (STZ)-induced apoptotic death of RIN-m5F cells, possibly due to the enhanced stability. The n0-STZ model, in which neonatal rats were injected with STZ at birth, developed a typical diabetic condition; however, chronic administration of [R(15, 20, 21), L(17)]-PACAP38 resulted in protection of pancreatic islets, followed by the improvement of glycemic control. Thus, the chemical modification of PACAP38 led to the development of a new promising derivative with enhanced stability and biological activity, and early administration of [R(15, 20, 21), L(17)]-PACAP38 might be of help for preventing the development of diabetes in type 2 diabetic model rats.

Liposomal formulations of glucagon-like peptide-1: improved bioavailability and anti-diabetic effect.

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is recognized to be potent drug candidate for treatment of diabetes, however its clinical application has been highly limited, because of rapid enzymatic degradation by dipeptidyl-peptidase IV. To protect GLP-1 from enzymatic degradation and improve pharmacological effects, liposomal formulations of GLP-1 were prepared using three types of lyophilized empty liposomes such as anionic, neutral and cationic liposomes. Electron microscopic and dynamic light scattering experiments indicated the uniform size distribution of GLP-1-loaded liposomes with mean diameter of 130-210 nm, and inclusion of GLP-1 did not affect the dispersibility and morphology of each liposome. Of all liposomal formulations tested, anionic liposomal formulation exhibited the highest encapsulation efficiency of GLP-1 (ca. 80%). In intraperitoneal glucose tolerance testing in rats, marked improvement of hypoglycemic effects were observed in anionic liposomal formulation of GLP-1 (100 nmol/kg) with 1.7-fold higher increase of insulin secretion, as compared to GLP-1 solution. In pharmacokinetic studies, intravenous administration of anionic liposomal formulation of GLP-1 (100 nmol/kg) resulted in 3.6-fold higher elevation of serum GLP-1 level as compared to GLP-1 injection. Upon these findings, anionic liposomal formulation of GLP-1 would provide the improved pharmacokinetics and insulinotropic action, possibly leading to efficacious anti-diabetic medication.