Joomi Lee

An Immunohistochemical Study of the Gastrointestinal Endocrine Cells in the C57BL/6 Mice

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) of the gastrointestinal tract of C57BL/6 mouse was studied with immunohistochemical method using seven types of specific anti‐sera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecystokinin (CCK)‐8. In this study, all the seven types of immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle in shape (open‐type cell) while cells showing round in shape (closed‐type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of gastrointestinal tract. CGA‐IR cells were demonstrated throughout the whole gastrointestinal tract and they showed most predominant in the pylorus and duodenum. Serotonin‐IR cells were detected throughout whole gastrointestinal tract and they showed highest frequency in the stomach and colon. Somatostatin‐IR cells were demonstrated throughout whole gastrointestinal tract except for large intestine and showed highest frequency in the fundus. HPP‐IR cells were found in the fundus with rare frequency. Peculiarly, glucagon‐IR cells were restricted to the fundus, ileum and colon with a few frequencies. Gastrin‐IR cells were restricted to the pylorus with numerous frequency and CCK‐8‐IR cells were observed in the pylorus, duodenum and jejunum with numerous and/or a few frequencies, respectively. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in C57BL/6 mouse.

Immunohistochemical Study on the Endocrine Cells in Gut of the Stomachless Teleost, Zacco platypus (Cyprinidae)

The regional distribution and relative frequency of neurohormonal peptides‐producing cells were demonstrated in the gut of the stomachless teleost, Zacco platypus (Temminck et Schegel), using 10 types of specific antisera raised against mammalian regulatory peptides. The gut of Z. platypus was divided into five portions from proximal to distal (segment I–V). Most of immunoreactive cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shape having long cytoplasmic process that was reached via the lumen while cells round in shape were found in the basal portions of epithelial lining occasionally. Serotonin‐, somatostatin‐, glucagon‐, cholecystokinin (CCK)‐8 and pancreatic polypeptide (PP)‐immunoreactive cells were observed in this study. However, no chromogranin A‐, secretin‐, vasoactive intestinal peptide (VIP)‐, substance P‐ and bombesin‐immunoreactive cells were found. Serotonin‐immunoreactive cells were demonstrated throughout the entire gut tract and occurred more frequently than other cells. Somatostatin‐immunoreactive cells were restricted to proximal segments of the gut (segment I–III) with rare frequencies, and glucagon‐immunoreactive cells were demonstrated in the proximal segments of the gut (segment I, II) with moderate to few occurences. CCK‐8‐immunoreactive cells were found throughout the whole intestinal tract except for most proximal segment (segment I) with moderate to few frequencies and PP‐immunoreactive cells were demonstrated in the proximal to middle segments, segment I–III, with a few, rare and rare frequencies, respectively.

Effect of age on the pharmacokinetics of fimasartan (BR-A-657)

Objectives: The aim of this study was to compare the pharmacokinetics (PK) and safety of fimasartan (BR-A-657), an angiotensin II receptor antagonist, between healthy young (19 – 45 years) and older (≥ 65 years) male subjects. Methods: To assess the effect of age on PK and safety, fimasartan was administered as a single 240 mg tablet to 12 young and 10 older male subjects, followed by serial blood sampling over 48 h. Plasma concentrations of fimasartan were analyzed using validated HPLC-MS/MS. Clinical and laboratory adverse events were assessed. Results: After oral administration of 240 mg fimasartan, the mean area under the plasma concentration-time curve from time zero to infinity (AUC0→∞) was 2899.0 ng/ml/h in the older, which was significantly greater than in young subjects (1767.4 ng/ml/h; p = 0.03). The geometric mean AUC0→∞ was 69.4% higher in older than in young subjects. The maximum plasma concentration (Cmax), time to reach Cmax and elimination half-life for fimasartan did not differ significantly between the older and young groups. Importantly, fimasartan was well tolerated during this study. Conclusions: While some PK parameters were statistically different between the two groups, the effect of age on the PK was modest (e.g., AUC increase < twofold in older subjects).

The Regional Distribution and Relative Frequency of Gastrointestinal Endocrine Cells in SHK-1 Hairless Mice: An Immunohistochemical Study

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, caecum, colon and rectum) of the gastrointestinal tract of SKH‐1 hairless mice were investigated using immunohistochemical methods and seven types of specific antisera against somatostatin, serotonin, glucagon, cholecystokinin (CCK)‐8, secretin, pancreatic polypeptide (PP) and gastrin. In this study, somatostatin‐, serotonin‐, glucagon‐, CCK‐8‐, secretin‐ and gastrin‐immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle‐shaped (open‐type cell) while cells that were round in shape (close‐type cell) were occasionally found in the stomach regions. Their relative frequencies were varied according to each portion of gastrointestinal tract. Somatostatin‐IR cells were found throughout the gastrointestinal tract except for the large intestine. Serotonin‐IR cells were detected throughout the whole gastrointestinal tract and were the most predominant endocrine cell types in this species of mouse. Glucagon‐IR cells were restricted to the fundus, occurring rarely. CCK‐8‐IR cells were observed in the pylorus, duodenum and jejunum with freuqencies that were numerous, moderate and few, respectively. Peculiarly, secretin‐IR cells were demonstrated in the whole intestinal tract with either few or rare frequencies. Gastrin‐IR cells were restricted to the pylorus and were numerous. However, no PP‐IR cells were found in this study. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in SKH‐1 hairless mouse.

An Immunohistochemical Study of Gastrointestinal Endocrine Cells in the BALB/c Mouse

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal tract (GIT) of BALB/c mouse were studied. Endocrine cells were stained using immunohistochemical method with seven types of antisera against bovine chromogranin (BCG), serotonin, gastrin, cholecystokinin (CCK)‐8, somatostatin, glucagon and human pancreatic polypeptide (HPP), and the regional distributions and their relative frequencies were observed in the eight portions of the GIT of BALB/c mice. All seven types of immunoreactive (IR) cells were identified. Most of the IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) while round‐shaped cells (closed type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies varied according to each portion of the GIT. BCG‐IR cells were observed throughout the whole GIT except for the rectum and they were most predominant in the pylorus. Serotonin‐IR cells were detected throughout the whole GIT and they showed the highest frequency in the fundus. Gastrin‐ and CCK‐IR cells were restricted to the pylorus and duodenum with a majority in the pylorus and rare or a few frequencies in the duodenum. Compared with other mammals, somatostatin‐IR cells were restricted to the fundus and pylorus with a few frequencies, respectively. In addition, glucagon‐ and HPP‐IR cells were restricted to the fundus and duodenum, respectively, with relative low frequencies. Some species‐dependent unique distributions and frequencies of endocrine cells were observed in the GIT of BALB/c mouse compared with other rodents.

An Immunohistochemical Study on the Endocrine Cells in the Alimentary Tract of the Red-Eared Slider (Trachemys scripta elegans)

The regional distribution and relative frequency of endocrine cells in the alimentary tract of the red‐eared slider, Trachemys scripta elegans, were investigated by immunohistochemical methods using 10 antisera. Most of the immunoreactive cells in the intestine were spherical or spindle‐like in shape (open‐type cells), while round cells (closed‐type cells) were occasionally found in the stomach. These immunoreactive cells were located in the basal portion of the intestine, including the oesophagus, and in the gastric glands of the stomach. Cg A‐immunoreactive cells were restricted to the pylorus and duodenum and were few in number. Serotonin‐immunoreactive cells, which were most commonly found in the pylorus, were found in the epithelia throughout the alimentary tract at various frequencies. Gastrin‐immunoreactive cells were found in the pylorus, duodenum and jejunum at moderate, low and very low frequencies, respectively. Somatostatin‐immunoreactive cells were found throughout the alimentary tract except for the rectum, at various frequencies. Glucagon‐immunoreactive cells were detected in the fundus, pylorus, jejunum and ileum at low or very low frequencies. CCK‐8‐immunoreactive cells were found in the pylorus, fundus and duodenum at very low, low and moderate frequencies, respectively. Bombesin‐immunoreactive cells were restricted to the fundus and pylorus at low frequencies. No secretin‐, BPP‐ or VIP‐immunoreactive cells were found in this study.

Rapid determination of sumatriptan in human plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application to clinical pharmacokinetic study

A sensitive and simple detection method coupling ultra-performance liquid chromatography with tandem mass spectrometry was developed and validated to analyze sumatriptan levels in human plasma. The plasma sample preparations for the analysis were based on liquid-liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS detection was performed on a triple-quadrupole tandem mass spectrometer by monitoring the protonated parent→daughter ion pairs at m/z 296→58 and m/z 388→71 for sumatriptan and terazosin (internal standard), respectively. The method was validated with respect to its specificity, linearity, sensitivity, accuracy, precision, recovery, and stability. The calibration curve was linear from 0.5 to 50 ng/mL (r>0.999). The mean extraction recovery for sumatriptan was higher than 62.3%. The method accuracy was within 97.4%, and the relative standard deviation of the intra- and inter-day precision values was within 11.7% at all quality control levels. Plasma samples that contained sumatriptan were stable under three freeze-thaw cycles, short- and long-term storage, and autosampler conditions. This method was successfully applied to a pharmacokinetic study conducted with 10 healthy volunteers. After oral administration of 50-mg sumatriptan and serial blood sampling over 12 h, the mean area under the plasma concentration-time curve from time 0 to 12 h and the maximum plasma concentration were 116.2 ng h/mL and 33.2 ng/mL, respectively.

The Regional Distribution and Relative Frequency of Gastrointestinal Endocrine cells in the Nude Mice, Balb/c-nu/nu: An Immunohistochemical Study

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract – fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the nude mouse, Balb/c‐nu/nu were studied with immunohistochemical method using six types of anti‐sera against serotonin, gastrin, cholecystokinin (CCK)‐8, somatostatin, glucagon and human pancreatic polypeptide (hPP). All of six types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. Serotonin‐IR cells were detected throughout the whole GI tract and they showed the highest frequency in the pylorus. Gastrin‐IR cells were restricted to the pylorus and duodenum with numerous and a few frequencies, respectively. CCK‐8‐IR cells were also restricted to the pylorus, duodenum and jejunum with numerous, a few and rare frequencies, respectively. Somatostatin‐IR cells were demonstrated throughout the whole GI tract except for the colon and rectum, and they showed the highest frequency in the fundus. In addition, glucagon‐ and hPP‐IR cells were restricted to the fundus and rectum, respectively with a few frequencies. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the nude mouse, Balb/c‐nu/nu was similar to that of other strains of mice. However, some strain and/or species‐dependent unique distributions and frequencies of endocrine cells were also observed especially for somatostatin‐ and hPP‐IR cells.

Calvarial slope affecting accuracy of Ghajar Guide technique for ventricular catheter placement

OBJECT The Ghajar Guide technique is used to direct a ventricular catheter at a 90° angle to the skull surface at Kochers point. However, the human calvaria is not completely spherical. Lateral to the sagittal midline, the calvaria slopes downward with individual variation and thereby affects the accuracy of ventricular catheter placement. Accordingly, the authors investigated the accuracy of the orthogonal catheter trajectory using radiographic simulation and examined the effect of the calvarial slope on this accuracy. METHODS A catheter trajectory orthogonal to the skull surface at Kochers point and the ideal catheter trajectory to the foramen of Monro were drawn bilaterally on coronal head images of 52 patients with hydrocephalus. The correction angle, the difference between the 2 catheter trajectories, was then measured. Meanwhile, the calvarial slope was measured around Kochers point by using a coronal head image. The correlation between the correction angle and factors such as the calvarial slope and bicaudate index was then assessed using a Pearson correlation analysis. RESULTS The ventricular catheter trajectory orthogonal to the skull at Kochers point in the patients with hydrocephalus led to a catheter trajectory into the ipsilateral (70.2%) or contralateral (29.8%) lateral ventricles. The correction angles ranged from -3.3° to 16.4° (mean ± SD 5.7° ± 3.7°). In 87 (83.7%) head sides, lateral deviation from the orthogonal trajectory was required to approximate the ideal trajectory, and the correction angle ranged from 2.0° to 16.4° (mean 6.7° ± 2.9°). The calvarial slope in the 104 head sides ranged from 15.6° to 32.5° (mean 24.2° ± 3.1°). Pearson correlation analysis revealed a strong positive correlation (r = 0.733) between the calvarial slope and the correction angle. CONCLUSIONS The accuracy of ventricular catheter placement using the Ghajar Guide technique is affected primarily by the calvarial slope around Kochers point. A radiographic analysis of a preoperative coronal head image can be used to estimate the accuracy of ventricular catheter placement and enable adjustment to approximate the ideal catheter trajectory.

Comparative Cost Analysis for Surgical and Endovascular Treatment of Unruptured Intracranial Aneurysms in South Korea

Objective A cost comparison of the surgical clipping and endovascular coiling of unruptured intracranial aneurysms (UIAs), and the identification of the principal cost determinants of these treatments. Methods This study conducted a retrospective review of data from a series of patients who underwent surgical clipping or endovascular coiling of UIAs between January 2011 and May 2014. The medical records, radiological data, and hospital cost data were all examined. Results When comparing the total hospital costs for surgical clipping of a single UIA (n=188) and endovascular coiling of a single UIA (n=188), surgical treatment [mean±standard deviation (SD) : ₩8,280,000±1,490,000] resulted in significantly lower total hospital costs than endovascular treatment (mean±SD : ₩11,700,000±3,050,000, p<0.001). In a multi regression analysis, the factors significantly associated with the total hospital costs for endovascular treatment were the aneurysm diameter (p<0.001) and patient age (p=0.014). For the endovascular group, a Pearson correlation analysis revealed a strong positive correlation (r=0.77) between the aneurysm diameter and the total hospital costs, while a simple linear regression provided the equation, y (₩)=6,658,630+855,250x (mm), where y represents the total hospital costs and x is the aneurysm diameter. Conclusion In South Korea, the total hospital costs for the surgical clipping of UIAs were found to be lower than those for endovascular coiling when the surgical results were favorable without significant complications. Plus, a strong positive correlation was noted between an increase in the aneurysm diameter and a dramatic increase in the costs of endovascular coiling.