Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells

OBJECTIVE: Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines. METHODS: Glioma cell lines (T-98 G and U-251 MG) were used for this study. RESULTS: The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells. CONCLUSION: Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.

Effect of a Denture Adhesive on the Satisfaction and Kinesiographic Parameters of Complete Denture Wearers: A Cross-Over Randomized Clinical Trial

The aim of the present study was to assess the effect of a denture adhesive (DA) on patient satisfaction and kinesiographic parameters of complete denture wearers by a cross-over study. Fifty edentulous patients received a set of new complete dentures. After an adaptation period, the participants were enrolled in the trial and randomized to receive a sequence of treatment protocols: Protocol 1- DA use during the first 15 days, followed by no DA for the next 15 days; Protocol 2- no DA during the first 15 days, followed by use of DA for the next 15 days. Outcomes were assessed after 15 days of each sequence of treatment. A questionnaire was used to assess the patients´ satisfaction. A kinesiograph was used to record mandible movements and patterns of maxillary complete denture movement during chewing. The Wilcoxon test (α=0.05) and a paired sample t-test (α=0.05) were used to compare satisfaction levels and kinesiographic data, respectively. Use of DA improved the overall level of patient satisfaction (p<0.001). The kinesiographic recordings revealed a significant increase (1.7 mm) in vertical mandible movements (p<0.001) during chewing and a lower (0.3 mm) vertical intrusion of the maxillary complete dentures (p=0.002) during chewing after using the DA. Use of DA in complete denture wearers improved the patients´ satisfaction and altered mandible movements, with increases in vertical movements during chewing and less intrusion of maxillary complete dentures.

O objetivo deste estudo foi avaliar o efeito da utilização de um adesivo para prótese na satisfação e nos parâmetros cinesiográficos em usuários de próteses totais por meio de um estudo "cross-over". Cinquenta pacientes desdentados receberam novas próteses totais bimaxilares. Após um período de adaptação, os participantes incluídos no estudo receberam uma sequência de tratamento: Protocolo 1- utilização do adesivo para prótese durante os primeiros 15 dias, seguida por não utilização do adesivo os próximos 15 dias; Protocolo 2- não utilização do adesivo durante os primeiros 15 dias; seguida por utilização do adesivo nos próximos 15 dias. Os resultados foram avaliados após 15 dias de cada sequência de tratamento. Um questionário para avaliar a satisfação dos pacientes e um cinesiógrafo para registrar os movimentos mandibulares e o padrão de movimento da prótese total maxilar durante mastigação foram utilizados. O teste de "Wilcoxon" (α=0,05) e o "t-test" de Student para amostras pareadas (α=0,05) foram utilizados para comparar o grau de satisfação dos pacientes e os dados cinesiográficos, respectivamente. O adesivo para prótese melhorou significativamente a satisfação geral dos participantes (p<0,001). Os registros cinesiográficos mostraram um aumento significativo (1,7 mm) no movimento mandibular vertical (p<0,001) e uma menor intrusão (0,3 mm) da prótese total superior (p=0,002) durante a mastigação após o uso de adesivo. O uso de adesivo para prótese melhorou a satisfação dos usuários de próteses totais e gerou um aumento no movimento mandibular vertical e uma menor intrusão da prótese total maxilar durante a mastigação.

Effect of mica monomer powder on chief and parietal cells as well as G and D cells in gastric mucosa of chronic atrophic gastritis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis (CAG) rats.</p><p><b>METHODS</b>Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa.</p><p><b>RESULTS</b>Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups.</p><p><b>CONCLUSION</b>Mica has the pharmacological action of protecting the gastric mucosa, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion (gastrin and somatostatin) by increasing the number of chief and parietal cells as well as G and D cells.</p>

Lipasa: una enzima singular por sus interacciones neuro-hormonales. (Revisión y análisis experimental y clínico) / Lipase: a particular enzyme because of its neuro-hormonal interactions

Un objetivo de esta presentación es el de analizar las peculiaridades distintivas de la enzima lipasa proveniente de diferentes fuentes: gástrica (LG), intestinal (LI)hepática (LH), lipoproteica (LLP), pero, en especial, aquella de la pancreática (LP), sobre todo en lo relativo a sus interacciones neuro-hormonales.

Ultrastructure of Rabbit Pyloric Mucosa Following Ligation of Common Bile Duct / 체질인류학회지

The purpose of this study was to examine the ultrastructural characteristic of the normal pylorus mucosa, and their structural changes induced by the ligation of common bile duct of the male rabbits weighing about 1.5 kg each. Experiment animals were divided into normal, sham operation, and experimental groups. Common bile duct ligation was performed under ether anesthesia and anjmals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after operation. The mucosal specimen of the pylorus, were fixed and embedded with common method. The sections were cut on a LKB-V ultratome, and observed under a JEM 100CX II electron microscope. The results were as follow : 1. In the early stages (1st, 3rd, 5th day groups) following the ligation, surface mucous cells have the various electron densities and shape of the mucous granules. In the late stages (7th, 14th day groups) following the ligation, many surface mucose cells containing numerous electron dense mucous granules are seen. 2. In the early stage of the ligation of bile duct, secretory function of EC cells was depressed, but in the later stage, the cells showed recovered secretory activity. 3. Secretory function of D cells was depressed on the early groups after the ligation of common bile duct, but they showed recovered secretory activity from the late groups after the ligation of the common bile duct. 4. Secretory function of G cells was activated on the early groups after the ligation of common bile duct, but they showed depressed secretory activity from the late groups after the ligation of the common bile duct. Considering the above findings, common bile duct ligation probably causes the dysfunction of the pyloric surface mucous cells that results in delayed mucous formation and secretion, and recovered mucous secretory function on the late stages. EC cells and G cells, depressed the secretory activities on the early stages and recovered on the late stages of the ligation of common bile duct. But D cells in the pyloric mucosa was activated on the early groups after the ligation of common bile duct ligation, but they was depressed secretory activities on the late groups.

Effect of mica monomer granule on gastrin, somatostatin and G cells as well as D cells of gastric mucosa in CAG rat / 中国中药杂志

<p><b>OBJECTIVE</b>To study regulative action of mica monomer granule preparation on gastrin (GAS), somatostatin (SS) and G cells as well as D cells of gastric mucosa in experimental chronic atrophic gastritis (CAG) rat.</p><p><b>METHOD</b>CAG rats were treated with mica monomer granule preparation with three different dosages--high, moderate and low level respectively. Changes of blood serum GAS, blood plasma SS and G cells as well as D cells of gastric mucosa in CAG rats were observed and detected with ELISA method, RIA method and immunocytochemistry method.</p><p><b>RESULT</b>Mica monomer granule of three different dosages could increase the quantity of G cells as well as D cells of gastric mucosa and the concentration of blood serum GAS and decrease the content of blood plasma SS in CAG rat at different level respectively. It was more effective in high and moderate dosage groups.</p><p><b>CONCLUSION</b>Mica has the pharmacological action of protecting gastric mucosa, promoting the palingenesis of gastric gland and enhancing blood stream of gastric mucosa consequently to abate the inflammation reaction of gastric mucosa. Its effective mechanism is associated with the neuroendocrine regulative mechanism of promoting the secretion of gastric acid and gastric pepsin by increasing the amount of G cells as well as D cells and the concentration of blood serum GAS, and reducing inhibiting action on GAS secretion and enhancing the secretion of GAS by decreasing the content of SS.</p>

Significance of CD99 Immunoreactive Cells in relation to Gastrin-producing Cells in Human Gastric Mucosa

BACKGROUND: CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroendocrine tumors and its immunoreactivity has also been reported in gastrointestinal neuroendocrine tumors. However, the normal distribution of CD99 reactive cells in gastrointestinal mucosa and their function are not fully understood. METHODS: We performed an immunohistochemical study using antibodies to CD99 and gastrin on formalin fixed and paraffin embedded tissue of the stomach. RESULTS: CD99 were strongly expressed in the gastric glands of neonate (3/3) and infant (1/1) cases but not detected in the fetal period (0/30). In adults, CD99 was observed in 36.8% (7/19). The number of CD99 positive cells were fewer in adult (3.48+/-6.43) than in neonate (5.66+/-0.58) and infant (11.33+/-2.21). CD99 was mostly located along the cytoplasmic membrane of glandular cells but cytoplasmic expression was also evident in neonate and infant cases. The G cells and CD99 expressed cells were reduced in the area showing intestinal metaplasia and atrophic change. As a result of the double stain, some of the G cells coexpress CD99 antigen, which were more in neonate (29%) than in adult (2.6%). CONCLUSIONS: The CD99 positive cells were found in the gastric pyloric antrum during the postnatal period and progressively reduced with age. This suggests the participation of CD99 protein in the differentiation and secretory process of neuroendocrine cells.

The Expression of Gastrin and Gastrin/ CCK-B Receptor mRNA in Cancer and Normal Tissue of Large Intestine

PURPOSE: Gastrin, a peptide hormone produced by the G cells of the gastric antrum, plays a major role in regulating acid secretion in the stomach, and acts as a trophic factor in the gastrointestinal tract. The relationship between gastrin and the development of colorectal cancer remains controversial. To study its possible role in development or proliferation of colorectal cancer, we evaluated the expression of gastrin and gastrin/CCK-B receptor mRNA in cancer and normal tissue from colorectal cancer patients. We also reviewed clinical records to evaluate the correlations between gastrin receptor expression and clinical characteristics of colorectal cancer. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate mRNA expression for gastrin and gastrin/CCK-B receptor in 26 surgical specimens of colorectal cancer. RESULTS: The mRNA expression of gastrin was detected in 24 out of 26 cancer specimens and 9 out of 26 normal colon specimens (p0.05). There was no significant correlation between gastrin receptor expression and clinical characteristics of colorectal cancer. CONCLUSIONS: The gastrin gene products might be more important than gastrin/CCK-B receptor in development or proliferation of colorectal cancer, which supports the hypothesis that gastrin gene products play a role in proliferation of colorectal cancer as an autocrine factor.

Fisiología gástrica / Gastric physiology

La secreción gástrica, como cada una de las funciones de nuestro organismo, requiere de una compleja integración de mecanismos neurales y endocrinológicos. El nervio vago y el sistema nervioso entérico, así como tres diferentes tipos de células (G, D, ECL) participan en la regulación de la función gástrica. La histamina es el principal secretagogo y tanto la vía nerviosa como la gástrica controlan la secreción de la misma. Esta sustancia actúa en receptores H2 que están unidos a proteína Gs, la cual activa a la adenilciclasa para que produzca AMPc y excite a la proteincinasa-C, que a su vez fosforila a la H+/K+ ATPasa. En esta revisión analizamos estos mecanismos.

Effect of Helicobacter pylori infection on antral gastrin and somatostatin cells and on serum gastrin concentrations

OBJECTIVES: Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted. RESULTS: Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001). CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.

Gastrin producing G-cells after chronic ethanol and low protein nutrition.

Male Wistar rats, (2 months old), randomly divided according to the diet offered to four groups (C-control; A- alcoholized, PD-protein-deprived, A-PD- alcoholized protein-deprived). In group A and A-PD rats, the number of gastrin producing G-cells was significantly lower. The volume density of G-cells was significantly decreased in alcoholic rats. Fasting serum gastrin level (FSGL) significantly raised due to combined effect of alcohol consumption and protein malnutrition. In group A rats, the profile area of G-cells and their nuclei increased. In PD rats, the profile area of G cells also increased. There were no differences in nucleus/cell ratio due to alcohol ingestion alone, but it decreased significantly in PD and A-PD rats. Pale and lucent types of granules were predominantly seen in G-cells of animals of group A and A-PD. Mean diameter of granules increased in A, PD and A-PD rats. Other endocrine cells (ECL, D, EC) also decreased in number in A rats. Somatostatin producing D-cells decreased significantly in A-PD rats, both in fundic and pyloric mucosa.

Serum Gastrin Levels in Relation to Helicobacter pylori Infection and Various Upper Gastrointestinal Diseases

PURPOSE: Gastrin secreted from antral G cell is a major hormone in regulation of gastric acid secretion. In adults, there are many reports that gastrin is correlated with H. pylori infection and peptic ulcer diseases, but those reports are rare in pediatric field. This study was done to research the serum gastrin levels in relation to H. pylori infection and various upper gastrointestinal diseases. METHODS: Upper gastrointestinal endoscopy was performed on 166 patients who visited OPD or were admitted to the Department of Pediatrics, Yonsei University College of Medicine between Aug. 1992 and Jul. 1994 due to recurrent abdominal pain and upper gastrointestinal bleeding. Detection of H. pylori infection was done by CLO test (rapidurease test) and Warthin-Starry silver stain using biopsied specimens, and the ELISA (Enzyme-linked Immunosorbent assay) test was done with their serum at the same time. Patients with any positive results were regarded as positive for H. pylori infection. Serum fasting gastrin levels were measured by I125 tagged radioimmunoassay. Statistical analysis was mode by the Student t test, mann-Whitney rank-sum and ANOVA multiple comparison test by BMDP, and the difference were taken as significant when p value below 0.05 RESULTS: 1) The mean serum gastrin level was significantly higher in H. pylori positive children (40.1+/-13.7pg/mL) than in negative children (29.5+/-7.5pg/mL). p value below 0.00005. 2) The mean serum gastrin level was 42.5+/-16.3pg/mL in duodenal ulcer patients, 36.9+/-17.9pg/mL in gastric ulcer, 34.4+/-9.9pg/mL in chronic superficial nodular gastritis, 30.2 +/-8.0pg/mL in superficial gastritis, 29.8+/-8.4pg/mL in normal group, and 30.7+/-4.2pg/mL in patients with other upper gastrointestinal diseases. The mean serum gastrin level of duodenal ulcer group was significantly higher than of normal or superficial gastritis group (p<0.01), but showed no significant difference with that of gastric ulcer or chronic superficial nodular gastritis group. 3) The serum gastrin level of H. pylori positive duodenal ulcer patients was significantly higher than those of H. pylori negative patients with other remaining gastrointestinal diseases including H. pylori negative duodenal ulcer group (p<0.05), and the serum gastrin level was significantly higher in H. pylori positive gastric ulcer patients than in H. pylori negative patients with other remaining gastrointestinal diseases including H. pylori negative gastric ulcer patients (p<0.05). In normal and superficial gastritis group, the serum gastrin level of H. pylori positive children was significantly higher than that of H. pylori negative children (p<0.05). There was no significant difference in the serum gastrin levels between chronic superficial nodular gastritis positive and negative group. CONCLUSIONS: The serum gastrin levels were significantly increased in H. pylori positive children, especially in H. pylori positive duodenal and gastric ulcer patients. It is assumed that H. pylori has a major role in the pathogenesis of peptic ulcer diseases inducing increase in gastrin release from antral G cells.

Serum Gastrin Levels in Relation to Helicobacter pylori Infection and Various Upper Gastrointestinal Diseases

PURPOSE: Gastrin secreted from antral G cell is a major hormone in regulation of gastric acid secretion. In adults, there are many reports that gastrin is correlated with H. pylori infection and peptic ulcer diseases, but those reports are rare in pediatric field. This study was done to research the serum gastrin levels in relation to H. pylori infection and various upper gastrointestinal diseases. METHODS: Upper gastrointestinal endoscopy was performed on 166 patients who visited OPD or were admitted to the Department of Pediatrics, Yonsei University College of Medicine between Aug. 1992 and Jul. 1994 due to recurrent abdominal pain and upper gastrointestinal bleeding. Detection of H. pylori infection was done by CLO test (rapidurease test) and Warthin-Starry silver stain using biopsied specimens, and the ELISA (Enzyme-linked Immunosorbent assay) test was done with their serum at the same time. Patients with any positive results were regarded as positive for H. pylori infection. Serum fasting gastrin levels were measured by I125 tagged radioimmunoassay. Statistical analysis was mode by the Student t test, mann-Whitney rank-sum and ANOVA multiple comparison test by BMDP, and the difference were taken as significant when p value below 0.05 RESULTS: 1) The mean serum gastrin level was significantly higher in H. pylori positive children (40.1+/-13.7pg/mL) than in negative children (29.5+/-7.5pg/mL). p value below 0.00005. 2) The mean serum gastrin level was 42.5+/-16.3pg/mL in duodenal ulcer patients, 36.9+/-17.9pg/mL in gastric ulcer, 34.4+/-9.9pg/mL in chronic superficial nodular gastritis, 30.2 +/-8.0pg/mL in superficial gastritis, 29.8+/-8.4pg/mL in normal group, and 30.7+/-4.2pg/mL in patients with other upper gastrointestinal diseases. The mean serum gastrin level of duodenal ulcer group was significantly higher than of normal or superficial gastritis group (p<0.01), but showed no significant difference with that of gastric ulcer or chronic superficial nodular gastritis group. 3) The serum gastrin level of H. pylori positive duodenal ulcer patients was significantly higher than those of H. pylori negative patients with other remaining gastrointestinal diseases including H. pylori negative duodenal ulcer group (p<0.05), and the serum gastrin level was significantly higher in H. pylori positive gastric ulcer patients than in H. pylori negative patients with other remaining gastrointestinal diseases including H. pylori negative gastric ulcer patients (p<0.05). In normal and superficial gastritis group, the serum gastrin level of H. pylori positive children was significantly higher than that of H. pylori negative children (p<0.05). There was no significant difference in the serum gastrin levels between chronic superficial nodular gastritis positive and negative group. CONCLUSIONS: The serum gastrin levels were significantly increased in H. pylori positive children, especially in H. pylori positive duodenal and gastric ulcer patients. It is assumed that H. pylori has a major role in the pathogenesis of peptic ulcer diseases inducing increase in gastrin release from antral G cells.

Immunocytochemical study on the somatostatin,serotonin and gastrin cells in the gastrointestinal tract of the percida / 대한해부학회지

No abstract available.