Comparison of laxative effects of fermented soybeans (Cheonggukjang) containing toxins and biogenic amines against loperamide-induced constipation mouse model

BACKGROUND/OBJECTIVES@#(Cheonggukjang) is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of (Cheonggukjang), which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of (Cheonggukjang), containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model.MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. (Cheonggukjang) (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. @*RESULTS@#The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. @*CONCLUSION@#These results show that (Cheonggukjang), containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats

BACKGROUND: Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals. METHODS: We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment. RESULTS: Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group. CONCLUSION: Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.

Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. METHODS: Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. RESULTS: Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. CONCLUSION: Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.

The Pancreatic Tissue Regeneration and Molecular Regulators / 대한해부학회지

Pancreas is a unique organ that produces and secretes digestive enzymes to alimentary tube and supplies endocrine hormones regulating metabolic homeostasis. In the postnatal stage, pancreatic tissue is maintained by a simple proliferation of the preexisting cells. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However regeneration of pancreatic tissue can be induced experimentally following pancreatic injuries in animal models. Regeneration occurs at the site of tissue injury by forming new lobules, so called 'neogenic lobule', that consist of the immature pancreatic tissues of both exocrine and endocrine components. We postulate that regeneration is instigated from the small tubular structures with elongated epithelial cells (neogenic ductules) which grow to ducts and acini for exocrine neogenesis, as well as to islet cells for endocrine tissue formation. As a sequential process of neogenic regeneration, the regenerating tissue becomes heterogeneous in tissue composition. Neogenic lobules in earlier regenerating stage were mainly composed of neogenic ductules which are substituted with developing acini in later stages. The endocrine cells, including insulin secreting beta cells, are also derived from the stem/precursor cells in neogenic ductules. After budding off from the neogenic ductules, the primitive endocrine cells continue to proliferate and differentiate, forming a large cell cluster or primitive islet. Such neogenic regeneration differs, but not completely, from pancreas development during fetal organogenesis. We found that the pancreatic regeneration is regulated by the several biological factors including nestin, clusterin and INGAP which are not involved in embryonic pancreas development. We suggest that the stem/precursor cells are recapitulated and regenerated to functional cells, and stem cell-derived pancreatic regeneration could provide a source of the pancreatic cells, particularly insulin secreting beta cells for cell replacement therapy of diabetes.

Pancreatic Exocrine and Endocrine Cell Differentiation during Pancreatic Regeneration / 한양의대학술지

Pancreatic tissue is maintained by a simple proliferation of the preexisting cells in adulthood, whereas, they are dynamically derived from precursor/ stem cells from ductal epithelia during prenatal life. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However, regeneration can be experimentally induced in the adult pancreas in response to various tissue injuries such as partial resection, pancreatitis by obstruction of the duct, and chemical insults. Regenerating pancreatic tissue shares a common morphogenic feature of "neogenic regeneration" in all regenerating animal models. Neogenic regeneration occurs at the site of tissue injury by forming small tubular structures with elongated epithelial cells (ductules) which grow to form pancreatic ducts and acini. The endocrine cells, including insulin secreting beta cells, are also derived from these ductules. As a sequential process of neogenesis, the regenerating tissue becomes heterogeneous in composition. Some areas were composed by tubules and ductules in surrounding loose connective tissue while others were denser with differentiating acini derived from tubules or ductules. Such neogenic regeneration mimics tissue development during fetal pancreatic organogenesis. In the process of pancreatic neogenesis, we found unique expressions of bioactive proteins such as nestin and clusterin as morphogenic factors. It is likely that the stem/precursor cells could be recapitulated and regenerated to functional cells, including endocrine and exocrine pancreatic cells with acinar and ductal cells during neogenic regeneration of the pancreas.

Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

The effects of taurine on plasma and liver cholesterol, erythrocyte ouabain sensitive Na efflux and platelet aggregation were examined in Sprague Dawley rats fed control or 0.5% cholesterol with 0.2% cholate diet. Plasma and liver levels of total cholesterol were increased significantly (p<0.05) in rats fed cholesterol diet compared to the control, and taurine significantly decreased the elevated plasma level of cholesterol in rats fed cholesterol diet (p<0.05). HDL-cholesterol was decreased in groups fed the cholesterol diet regardless of taurine supplementation and the difference between groups with and without cholesterol was significant (p<0.01). Plasma triglyceride was decreased and liver triglyceride was increased both significantly (p<0.05) in rats fed cholesterol compared to the control. Plasma and liver triglyceride in rats fed taurine was decreased significantly compared to the control (p<0.05). Intracellular Na tended to be lower in rats fed cholesterol or taurine and higher in rats fed cholesterol plus taurine compared to the control. Na efflux through Na-K ATPase and the passive leak of Na was somewhat reduced in rats fed cholesterol or taurine and was augmented in rats fed cholesterol plus taurine compared to the control, which showed a similar trend to the intracellular Na. Taurine supplementation caused a suppression of Na efflux in groups fed control diet and restored the suppressed Na efflux in groups fed cholesterol. Platelet aggregation was significantly decreased in the group fed taurine compared to the control (p<0.05) and the group fed cholesterol plus taurine was also a little lower in aggregation than the group fed cholesterol. Microscopic examination showed that taurine prevented fatty liver in rats fed cholesterol diet. Taurine known for stimulating Na-K ATPase in some cell types rather decreased erythrocyte ouabain sensitive Na-K ATPase in the present study. Taurine had hypolipidemic and hypocholesterolemic effects and inhibited platelet aggregation which may be favorable for prevention of cardiovascular diseases.

Effect of Treadmill Exercise Training and Dietary Intake of Garcinia Cambogia Extract, Soypeptide and L-Carnitine Mixture on Body Weight Reduction in Rats Fed High-Fat Diet

This study was undertaken to examine effects of dietary intake of garcinia cambogia extract, soy peptide and L-carnitine mixture on body weight gain and obesity-related bio-markers in rats fed high-fat diet for 9 weeks with or without regular treadmill exercise. Forty 5-week-old male Sprague-Dawley rats were randomly divided into four groups; sedentary control group (SC), exercised control group (EC), sedentary formula-fed group (SF), and exercised formula-fed group (EF). The SC and EC rats were fed high-fat control diet (fat comprises 40% of total caloris), and SF and EF rats were fed high-fat formula (composed of garcinia cambogia, soy peptide and L-carnitine) supplemented diet. Statistical analyses by two-way ANOVA indicated that the regular treadmill exercise significantly lowered cumulative body weight gain, total visceral fat mass, and epididymal, perirenal and retroperitoneal fat pad weights, and serum concentrations of total cholesterol and LDL + VLDL cholesterol, insulin, c-peptide and leptin. Feeding the formula also resulted in significant reductions in cumulative body weight gain and visceral fat pad weights, along with other related parameters including serum total and LDL + VLDL cholesterol levels, and hepatic enzyme activities involved in fatty acid synthesis. Statistical analyses by one-way ANOVA revealed that the formula consumption significantly improved body weight gain (18% reduction), total visceral fat weight (20% reductions), and serum total (43% reduction) and LDL + VLDL cholesterol (54% reduction) levels, as well as serum levels of insulin (49% reduction), and c-peptide (41% reduction) in sedentary rats, but failed to exhibit significant reductions in these indices in animals under treadmill exercise program. Taken together, these results suggest that the treadmill exercise per se exhibited significant improvements in body fat reduction and other related bio-markers, and so the formula consumption did not achieve a further significant reductions in these bio-markers in exercised rats. Nevertheless, animals fed the formula with regular exercise showed the most efficient weight reduction compared to other groups either fed formula without exercise or received regular exercise without dietary supplementation.

Stem Cell In Adult Pancreas: Its Activation and Induction of Beta Cell Differentiation / 대한해부학회지

Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stem cells could evolve from the duct system in response to neogenic stimulation. Following partial pancreatectomy (Px), we found extensive formation of ductules consisting of nestin-positive epithelial cells with higher replicating ability in the neogenic foci after Px. The neogenic ductules were isolated for the culture of nestin-positive duct cells. These nestinpositive duct cells were numerous and displayed extensive self-replication in the duct cell explants, thus depicted as nestin-positive duct stem (NPDS) cells. Endocrine cells, mostly insulin cells were present in the explants at day 2 as single cells or as small clusters adjacent to the NPDS cells, and formed islet-like masses at day 3 of culture, implying islet cell differentiation from NPDS cells. We found transient up-regulation of PDX-1 expression by RT-PCR at day 3 after Px in pancreatic tissue. We investigated the effect of clusterin overexpression on differentiation of insulin beta cells from duct cells We found that the number of insulin producing cells increased 11.5 fold when clusterin was overexpressed. Insulin expression, both insulin mRNA and peptide levels, was increased in clusterin cDNA transfected cells. In conclusion, we suggest that NPDS cells could be generated from adult pancreas by neogenic motivations and they may differentiate into insulin-secreting-cells, and clusterin could stimulate not only differentiation of precursor cells in the pancreatic duct, but also proliferation of predifferentiated beta cells. Those differentiated beta cells are functional cells secreting insulin in response to glucose stimulation.

Effects of Amantadine Therapy on Seizure Development in the Patients with Brain Injury and Stroke

OBJECTIVE: The objective of this study was to evaluate incidence and risk factors of seizure development during amantadine therapy for the patients with brain injury and stroke. METHOD: Thirty subjects (15 subjects with traumatic brain injuries and 15 subjects with strokes) who received a 4-week trial of amantadine from 100 mg/day to 400 mg/day were included. Control group, 40 patients (20 subjects with traumatic brain injuries and 20 subjects with strokes), did not take any brain stimulant. There were no differences in number, age, lesion area, and cognitive levels between two groups. Incidence of seizure in two groups was evaluated. RESULTS: Seizure occurred in 9 subjects in therapy group (30%) and in 1 subject in control group (2.5%). There was higher incidence of seizure in the group treated with amantadine than in the control group. In therapy group, most of the seizures occurred in high dose of 400 mg/day. CONCLUSION: Amantadine in high dose appeared to be associated with higher incidence of seizure. This study suggested that administration of amantadine in high dose in management of brain injury and stroke should be accompanied with careful monitoring of seizure.

Cyto-protective Effects of Aqueous Extract from the Gall of Rhus chinensis on Pancreatic Beta-cell / 대한해부학회지

We have previously reported that aqueous extract of gall from Rhus chinensis, known as "Obaeja", inhibited rat intestinal alpha-glucosidase and suppressed postprandial hyperglycemia by delaying digestion and absorption of intestinal carbohydrate (Shim et al., 2003). This led us to speculate that obaeja could be involved in ameliorating beta-cell injury by lowering glucotoxicity. In the present study, we thus examined the protective effect of obaeja on pancreatic beta-cell damage along with its anti-diabetic effect in streptozotocin-induced animal models. Streptozotocin was administered to rat pups (neonate/STZ model), or to adult rats with a lower dose using osmotic pump (osmotic pump/STZ model) for inducing beta cell death and diabetes. Obaeja was given to those rat pups after weaning in neonate/STZ model, or 2 weeks before subcutaneous implantation of osmotic pump to rats of the other latter model. In the diabetic control rats of the neonate/STZ model, which were not fed with obaeja, some pancreatic islets demonstrated a destruction of beta cell mass with insulitis 2 weeks after weaning, while some larger and irregular islets were formed by proliferation of alpha cells. In particular, we found some pancreatic lobules showing a severe inflammation and degeneration of islet and acinar tissues in this model. Islets in these inflammatory lobules were smaller in size with only few cells. In contrast, any inflammatory responses and insulitis were not observed in pancreas of the rats fed obaeja in this model. The islets in those rats maintained their normal profiles and islet cell population. Such anti-cytotoxic effect was also monitored in the diabetic rats of osmotic pump/STZ model. Especially, occurrence of hyperglycemia in the obaeja fed rats was delayed by 25~30 days than that of diabetic control rats in this model. Taken together, these results imply that regulation of postprandial blood glucose level by obaeja feeding may ameliorate a secondary injury caused by glucotoxicity.

Stimualtion of Beta Cell Neogenesis by SBTI (Soybean Trypsin Inhibitor) or Soybean Diet in the Subtotal Pancreatectomy Models / 대한해부학회지

The present study was performed to corroborate our hypothesis that soybean diet or SBTI treatment could stimulate neogenic regeneration of pancreatic beta cells, but also increase insulin synthesis and secretion from the beta cells for correction of hyperglycemia and diabetic symptoms. We, thus, monitored the beta cell regeneration in the neogenic pancreas as well as the changes of the blood glucose and insulin levels after subtotal pancreatectomy. The diabetic animals with hyperglycemia induced by the subtotal pancreatectomy showed recovery of blood glucose level toward the normal range (<150 mg/dl) by giving raw soybean for 3~4 weeks. Most animals treated with SBTI remained in euglycemic condition in spite of diabetic induction by subtotal pancreatectomy. Their serum insulin level was also recovered to the level of normal control, indicating the increased insulin synthesis and secretion from the neogenic beta cells. Neogenic area was enlarged at least 2 times in the pancreatectomized rats with dietary soybean or SBTI treatment, when compared with their pancreatectomized controls without any dietary treatment. In neogenic tissue, few endocrine cells were detected as a single cell or cell cluster at 3 days, and they formed primitive islet at 7 days after pancreatectomy in non-treated controls. The numbers of beta cells as well as alpha cells were considerably increased in the SBTI treated rats, and early formation of primitive islets were found in the neogenic tissue of those animals at 3 days after pancreatectomy. Those beta cells demonstrated a strong immunoreactivity for insulin, indicating their bioactive insulin secretion. Clusterin, a marker protein for pancreatic neogenesis, was expressed in the wider pancreatic area and at earlier stage after pancreatectomy when compared with non-treated control rats, indicating acceleration and stimulation of neogenesis of pancreas by stimulating proliferation and differentiation of the functional pancreatic cells. Taken together, we concluded that dietary soybean and SBTI could stimulate beta cell neogenesis and induce activation of insulin synthesis and secretion from the neogenic beta cells for correction of glucose homeostasis in diabetic subjects.

Attitude and knowledge of residents on domestic violence

BACKGROUND: Nowadays there is an upsurge of, social concern on domestic violence. The role of doctors in the prevention and screening of domestic violence is becoming important. Therefore, we selected medical residents to find out about the attitude and knowledge of doctors on domestic violence. METHODS: From 2000 March to October, we surveyed questionnaires to residents. The contents included the attitude on the victims, assailants and the children of domestic violence, whether they had the will to report domestic violence to the police or not, and finally the knowledge about the law on domestic violence. RESULTS: Among 210 residents, 95 (45.2%) answered. Almost 90% of the subjects agreed to the necessity of social intervention on the assailants. And most residents agreed that the psychosocial impact of domestic violence to the exposed children was important. 65 (68.4%) residents said they would report to the police when they recognized victims of domestic violence during their consultation. 27-68% answered correctly about the law related to domestic violence. 40% agreed to the need of education for domestic violence. CONCLUSION: The residents had little knowledge on domestic violence law. Therefore, it is essential for residents to be educated accordingly. The factors of marital status and sexual difference of doctors on domestic violence should be investigated.

Dysphagia associated with Jugular Foramen Syndrome due to Traumatic Brain Injury

OBJECTIVE: To present one case of dysphagia associated with jugular foramen syndrome (Vernet syndrome) by trauma. The jugular foramen syndrome refers to paralysis of the IX, X and XI cranial nerves. Dysphagia due to jugular foramen syndorme without pseudobular palsy is rare in traumatic brain injury. CASE SUMMARY: A 16-year-old boy with the left occipital skull fracture and skull base fracture was not able to take any food by mouth. There was no other significant symptom without dysphagia. Physical examination, laryngoscopic examination and electromyography revealed paralysis of the left IX, X and XI cranial nerves. Videofluoroscopic examination demonstrated atonic ballooned pyriformis sinus and closed upper esophageal sphincter. Brain CT and MRI showed fracture line in the left jugular foramen without brain stem or diffuse cortical lesion. Feeding gastrostomy was performed. CONCLUSION: We report an unusual case of dysphagia due to jugular foramen syndrome in traumatic brain injury patient.

The Usefulness of Supine Position on Swallowing of Liquid Diet in Neurogenic Dysphagia: Comparison with Sitting Position

OBJECTIVE: The purpose of this study is to find the proper feeding posture for the safe liquid meal in the patients with neurogenic dysphagia. METHOD: Fifty patients of neurogenic dysphagia with tracheal aspiration diagnosed with the videofluoroscopic swallowing test (VFST) were evaluated. VFST using 5 cc of barium solution was done for each patient in the sitting and supine position. The results of VFST of supine position were analyzed and compared with those of sitting position for the tracheal aspiration, laryngeal penetration, premature leakage, and laryngeal spillage. RESULTS: The incidence of premature leakage, tracheal aspiration, and laryngeal penetration is significantly decreased in the supine position (56%, 14% and 46%) compared to the sitting position (96%, 100% and 100%) (p<0.001). The incidence of laryngeal penetration referable to the swallowing reflex is significantly decreased in the supine position (0%, 46%, 0%) compared to the sitting position (14%, 96%, 44%) (p<0.001). The incidence of nasal regurgitation is 2% in the sitting position and 30% in the supine position. CONCLUSION: The incidence of tracheal aspiration of liquid diet is significantly decreased in the supine position compared to the sitting position. The supine position would be safer than the sitting position in the feeding of liquid diet.

Carpal Tunnel Syndrome in Chronic Renal Failure Patients Undergoing Continuous Ambulatory Peritoneal Dialysis(CAPD) / 대한신장학회잡지

BACKGROUND: Carpal tunnel syndrome(CTS) is a long-term complication in dialysis patients which results from compression of the median nerve within the carpal tunnel. It has been reported to occur with increased frequency in the hemodialysis population, but, there are few reports concering long-term complications in CAPD because of the relatively shorter duration of dialysis in most CAPD patients. The aim of this study was to determine the incidence of CTS in patients undergoing CAPD. METHODS: We analyzed 21 chronic renal failure (CRF) patients(males 14, females 7; age range 19-79 yr) undergoing CAPD. The patients were evaluated by questionnare, physical examination, and nerve conduction test(NCT). Age, gender, duration of CRF before CAPD, duration of CAPD, diabetic history were determined. RESULTS: Among the total 21 patients undergoing CAPD, only 5 patients(24%) were CTS, diagnosed by NCT. Two of these patients were symptomatic CTS, three patients were non-symptomtic CTS. So, there were no relationship between the incidence of CTS and clinical symptoms. Among the diabetic dialysis patients, the incidence of CTS was 28.57%. Also there was no increase in the number of diatetic patients with CTS. CONCLUSION: It is concluded that the incidence of CTS in CAPD patients was similar with the previous reported incidence(2-31%) of hemodialysis patients. Since CTS is treatable, annual or even semiannual nerve conduction tests is indicated all CRF patients on chronic dialysis.

Regulatory Effects of Nitric Oxide (NO) on Pancreatic Exocrine Secretion / 대한해부학회지

Recently nitric oxide (NO) is known as a bioactive molecule modulating secretory activity in various glandular tissues. Previously we have localized bNOS, a neuronal isoform of nitric oxide synthase, in the pancreatic tissue, particularly in the pancreatic islet of Langerhans and in the neurons of intrapancreatic ganglia. It implies that NO may play the important roles in regulation of pancreatic secretion by transmitting the neuronal signals from autonomic nervous system to endocrine and/or exocrine system of pancreas. We also revealed that NO is involved in regulation of insulin secretion and its synthesis. The present study was designed to elucidate the regulatory effect of NO on the pancreatic exocrine secretion by way of insulo-acinar axis. For the experiment, we observed modification of amylase secretion in the rats treated with N(G)-nitro-L-arginine-methyl ester (NAME), a potent NOS inhibitor. In addition, we observed the expression of clusterin which is known to be a protein associated with cell viability in order to assess the cytotoxic effect of NO. The present study showed that the intra-pancreatic NO is involved in regulation of amylase secretion of pancreatic acinar cells. Amylase immunoreactivity was significantly decreased at 60 and 90 min after NAME injection, although little change was seen during 30 min after treatment. However, the amylase immunoreaction was recovered toward the normal range at 120 min after NAME treatment. In electron-immunolabeling experiment, we observed the secretory granules with higher electron density, but less immunolabeling for amylase at 60~90 min after NAME treatment, while they restored normal feature and labeling density at 120 min. Clusterin expression increased along with the time course of experiment and demonstrated a highest level at 120 min after NAME injection. Taken together, the above results indicate that lowered level of NO induced by NAME treatment reduces amylase secretion of acinar tissue. It implies that increased level of NO in physiological range may stimulate pancreatic exocrine secretion.

Transplantation of Langerhans islet into digestive organs of the diabetic rat / 대한해부학회지

Although replacement therapy with insulin can prevent acute metabolic disorder in patients with IDDM (insulin dependent diabetes mellitus), it does not permanently restore glucose homeostasis. Recently it has been reported that islet transplantation could completely correct the glucose metabolic abnormalities and prevent further progression of the secondary complications of IDDM. For successful transplantation, the isolated islets should be prepared without loss of viability, while their immunogenicity being suppressed to reduce graft rejection. The present study was aimed to determine the optimal condition of islet culture, and to transplant them into the digestive organs including gastroin-testinal wall and salivary gland. For islet culture, pancreatic islets were isolated by a modified collagenase digestion technique from rats and cultured for 24, 48 and 72 hours in RPMI-1640 containing 0, 5.6 and 16.7 mM glucose. The viability of islets was evaluated by detection of insulin mRNA expressed in islet beta-cells using the in-situ hybridization and northern blot analysis, while their insulin content was examined by immunocytochemistry. Insulin mRNA was significantly reduced after 48 hours of culture in the islets incubated with absence of glucose, while distinct immunoreaction for insulin remained in the same islet. On the other hand, the islets cultured with normoglycemic (5.6 mM glucose) and hyperglycemic (16.7 mM glucose) conditions showed a normal or excessive transcription of insulin gene after 72 hours, respectively. These results indicate that biosynthetic activity of islets could be maintained longer than 72 hours without alteration of viability when they were cultured in normoglycemic condition. Therefore, we used islets cultured for 72 hours with 5.6 mM glucose for transplantation. The islets were implanted into the submucosal wall of the stomach and duodenum as well as into the parenchyme of the submandibular gland of the streptozotocin-induced diabetic rats. The transplanted islets in the gastrointestinal wall were abolished in 72 hours, while the islets injected into the submandibular gland retained normal cellular structure with viability for longer period. The beta-cell in the submandibular gland showed similar immunoreactivity for insulin compared to that of normal islets. However, they showed gradual infiltration of lymphocytes and beta-cell destruction at 10~14 days after transplantation. We suggested that the submandibular gland could be recommended as an alternative site for islet transplantation, because it is very easy to access for transplantation and provides the structural and functional similarities to pancreas in which the islets spontaneously grow.

Scapulohumeral Rhythm of Hemiplegic Patients by Plain X-ray Examination

OBJECTIVE: 1. To determine the difference of scapulohumeral rhythm (SHR) between the affected and unaffected side in hemiplegic patients. 2. To discover the influencing factors on altered scapulohumeral rhythm of affected side in hemiplegic patients. METHOD: Fifteen hemiplegic subjects, 18 to 54 years of age, participated in this study. Subjects were divided into two groups according to muscle tone on the basis of modified Ashworth scale (MAS). Plain X-ray of the shoulders were taken in neutral, 90 degree abduction, and full elevation of the arm in both affected and unaffected side. The arm angle, scapula angle, and glenohumeral angle were recorded for each individual in each of the three positions. RESULT: In the unaffected shoulders of hemiplegic patients, the mean values of SHRs from neutral to the 90o and from neutral to the 180o were 1 : 1.82 and 1 : 2.12, respectively. In the affected shoulders, the mean values of SHRs between 0~90o abduction and 0 to full abduction were 1 : 2.35 and 1 : 2.25, respectively. The mean value of SHRs from neutral to 90 degree of affected side was significantly decreased than unaffected side in the low tone group and increased in the high tone group (p<0.05). In addition, the SHRs of hemiplegic shoulders were significantly increased in the high tone group than the low tone group (p<0.05). CONCLUSION: Spasticity tends to result in decreased motion of scapula, which alters the SHR. A glenohumeral-to-scapulothoracic ratio of hemiplegic shoulder could be affected by spasticity and presence of subluxation.

Therapeutic Range of Serum Carbamazepine Concentration in Agitated Brain Injured Patients

OBJECTIVE: To determine the optimal therapeutic range of serum carbamazepine concentration in agitated brain injured patients. METHODS: Five traumatic brain injured patients exhibiting agitated behavior were treated with carbamazepine during acute rehabilitation. Carbamazepine dose was increased from 400 mg to 1600 mg gradually and blood samples were analyzed for serum carbamazepine concentration. The presence and degree of posttraumatic agitation was measured by the Agitated Behavior Scale (ABS) developed by Corrigan. Therapeutic serum concentration of carbamazepine was defined as serum carbamazepine concentration at a point of time maintaining the ABS scores below 21. RESULTS: After carbamazepine therapy, ABS score was changed from 36.2 to 19.8 and the therapeutic serum concentration of carbamazepine was 10.18 ug/ml on average. Experienced adverse effects were drowsiness, gastrointestinal trouble, slurred speech, headache, leukopenia, abnormal liver function test, hair loss, skin rash, and double vision. But most of these adverse effects were mild, transient, and reversible with an adjustment in dosage or rate of dosage increase. CONCLUSION: In the agitated brain injured patient, success in controlling the agitated behavior requires raising the dose of carbamazepine to high serum concentration levels above 10 ug/ml, as long as adverse effects do not intervene. Therefore we suggest that the therapeutic range of serum carbamazepine concentration for agitated brain injured patients is above 10 ug/ml.