Impaired synthesis of retinol-binding protein and transthyretin in rat liver with bile duct obstruction

To gain further insight into the protein metabolism in bile duct-obstruction, we examined the synthesis of retinol-binding protein (RBP) and transthyretin (TTR) in rats with common bile duct-ligation. In these rats, liver and plasma levels of RBP and TTR decreased markedly, whereas liver retinoid contents remained unchanged. Although there appeared no decrease in the total amount of RBP or TTR mRNA expressed in the liver, the subcellular distribution of these mRNAs changed from the membrane-bound polysome fraction to the membrane-unbound polysome fraction. This abnormal distribution recovered rapidly after biliary drainage, resulting in the subsequent recovery of the plasma RBP and TTR levels. These observations suggest that cholestasis inhibits the synthesis and secretion of RBP and TTR by disrupting the binding of their mRNAs to membrane-bound polysomes. Plasma levels of RBP and TTR might be sensitive indicators of the recovery of protein synthesis after biliary drainage in patients with obstructive biliary disorders.Supported in part by Grant-in-Aids from the Ministry of Education, Science and Culture (05770350 to M.O.; 05670463 to H.M.; 07780553 to S.K.) and by a grant from the Ryoichi Naito Foundation for medical research (to S.K.).     

Accuracy and Utility of a New Reflectance Pulse Oximeter for Fetal Monitoring during Labor

Objective. To evaluate the accuracy of a new pulse oximeter inestimating the oxyhemoglobin (O₂Hb) concentration in fetalarterial blood (SaO₂) with either a high concentration ofhemoglobin F (HbF) or a low concentration of O₂Hb duringlabor. Patients and Methods. Fetal forehead arterial oxygenation wasdetermined in 44 fetuses by reflectance pulse oximeter (SpO₂)during labor and was compared with SaO₂ determined immediatelyafter birth. Because HbF has little or no known effect on pulse oximetry, butdoes affect the laboratory multiwavelength CO-oximeter typereading, the SaO₂ was corrected by HbF concentration.SpO₂ and SaO₂ were simultaneously measured infive hypoxic adult volunteers achieved by inhaling 11% oxygen. Results.A gradual decline in HbF concentration was seen during weeks 37 to 40 ofgestation. HbF concentration varied near term, ranging between 53 and 88% ofthe fetal hemoglobin concentration (mean ± SD = 74.6 ± 6.3%).This alteration produced a lower %O₂Hb percentby 4% at the most. The corrected SaO₂ in cord blood correlatedwith fetal SpO₂ (y = 0.974, x –7.279, r = 0.90). In five adults, SpO₂ reflected wellSaO₂ with a mean ± SD of bias of –1.1 ± 2.9%. Conclusions.SpO₂ determined by a new reflectance pulse oximeter at theend of labor correlated with an immediate post-natal cord arterial bloodsample before the first breath, with a mean and SD of bias of 8.5 ±6.2%. Reflectance pulse oximetry is a useful tool for continuousnoninvasive monitoring of the fetal oxygen status during labor.     

High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts

Background: Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high‐glucose medium as a model of DM. Methods: PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)‐(κB signaling pathway. The involvement of NF‐κB was investigated with a specific NF‐κB inhibitor in PDLSCs under hyperglycemic conditions. Results: High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF‐κB activation and subsequent interleukin (IL)‐6 and IL‐8 expression. Treatment with an NF‐κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL‐6 expression caused by the high‐glucose environment. Conclusion: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.     

Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and pancreatic polypeptide release after solid-meal ingestion in man

The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin E₁ methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release after solid meal ingestion, was investigated in man. A radionuclide technique was used to measure gastric emptying of eight healthy volunteers. In addition, four parameters [SI (starting index): the lag time in the start of emptying;K value: the emptying rate;T1/2: the half emptying time; 120 min RR: the percent retention at 120 min] were determined for evaluation. Also, the PP response was analyzed according to two parameters: IPPR_SI, the integrated PP response for periods up to SI, and IPPR₁₂₀, the integrated PP response for 120 min. The results demonstrated that 5 g of orally administered ornoprostil significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min RR,P<0.05). However, ornoprostil affected neither the basal PP concentrations nor the cephalic phase of PP secretion which was determined as IPPR_SI. This thus suggests that ornoprostil affects the gastric motor function without interfering with the vagal-cholinergic pathway to the stomach.     

A case of bleeding duodenal ulcer with pemphigus vulgaris during steroid therapy

We report a rare case of bleeding duodenal ulceration in the different form of pemphigus vulgaris (PV). A 52-year-old female was diagnosed with acute pharyngitis and administered methylprednisolone. After several days, melena and many blisters were noted on her body. Endoscopy revealed blood oozing from the second part of a duodeneal ulcer around the major duodenal papilla. After initial endoscopic hemostasis, we observed a large regional, shallow duodenal ulcer. The blisters were suspected to represent the Nikolsky’s sign. The histological findings of her skin were characterized by suprabasal acantholysis and mixed inflammatory cell infiltrates, including scattered eosinophils. There were no other significant findings on skin biopsy or by direct immunofluorescence. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein 3 autoantibodies in her serum, and the patient was finally diagnosed with mucosal-dominant PV. Although we performed multiple biopsies from the esophagus, stomach and duodenum, the samples did not contain significant findings to enable us to distinguish from pemphigus vulgaris. Corticosteroids remain an essential component of PV treatment. When clinicians encounter PV development during steroid therapy, upper gastrointestinal complications should be considered and diagnostic endoscopy conducted.     

Hemodynamic effects of benazepril,an angiotensin-converting enzyme inhibitor,as studied in conscious normotensive dogs

Hemodynamic effects and inhibitory effects on the pressor response to exogenous angiotensin I of benazepril (CGS 14824A), a new angiotensin-converting enzyme (ACE) inhibitor, were examined in conscious chronically instrumented normotensive dogs in comparison with those of captorpil. Oral administration of benazepril (1-10 mg/kg) and captopril (3 and 10 mg/kg) reduced the blood pressure and inhibited the pressor response to angiotensin I dose-dependently. The blood-pressure-lowering effect of benazepril was as potent as that of captopril. The onset of effects of benazepril was slower and the duration longer than that of captopril. There was no close correlation between the attenuation of pressor response to exogenous angiotensin I and the blood-pressure-lowering effect of these two agents. These results indicate that benazepril is a potent ACE inhibitor with a slow onset and a long duration. The slow onset of action may be explained by the necessity of prior conversion of this compound to an active metabolite. A mechanism or mechanisms other than that responsible for the inhibition of pressor response to exogenous angiotensin I must be taken into consideration to explain the blood-pressure-lowering effects of benazepril and captopril.     

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.     

Endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy using balloon-assisted enteroscope

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy involves challenging procedures for ERCP endoscopists. In these patients, the anatomical structure of the intestine is substantially altered, and an endoscope needs to be inserted into the long afferent limb. Moreover, the papilla is observed in the opposite view from the normal anatomy. Recently, a balloon-assisted enteroscope (BAE) has been developed and made available for use in daily practice. The two types of BAE are single-balloon enteroscope (SBE), which is inserted with one balloon attached to the overtube using a balloon-assisted method, and double-balloon enteroscope (DBE), which is inserted with two balloons, one attached to the overtube and the other attached to the tip of the enteroscope. In addition, short-type DBE (short-DBE) and short-type SBE (short-SBE) with a working length of approximately 150 cm, which could be used with various ERCP accessories, are commercially available or under development. Notably, the success rate of ERCP through coordinated manipulation with a balloon was remarkably improved with the use of BAE, even in patients with surgically altered anatomy. Here, we report the current status and procedures of ERCP in patients with surgically altered anatomy.     

Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population

Background

The prevalence of diabetes mellitus (DM) has been increasing. The present study was carried out to examine the relationship between this increase and fatty liver.

Methods

Japanese participants who underwent regular health examinations in 1991, 1996, 2001, 2006, and 2011 were enrolled. Fatty liver was diagnosed using ultrasonography. DM was defined as requiring the use of medication for DM, having a fasting blood glucose level ≥126 mg/dl, or hemoglobin A1c level ≥6.5 %.

Results

Logistic regression analysis on data from 11,235 participants (6,882 men and 4,271 women) in 2011 revealed that the association between fatty liver and DM was independent of age, body composition, and other confounders [odds ratio (OR) 1.97, 95 % confidence interval (95 % CI) 1.66–2.32 in men, and OR, 3.12; 95 % CI, 2.29–4.26 in women]. In 2006, 5,318 participants did not have DM and were able to be followed up in 2011. Fatty liver in 2006 was an independent predictor of DM in 2011 [OR 1.73 (95 % CI 1.20–2.50) in men, 4.13 (2.16–8.10) in women]. The prevalence of DM increased significantly during the 20-year period examined among both men (6.0, 8.9, 10.0, 10.8, 12.0 %, P < 0.001) and women (3.3, 4.5, 4.2, 4.1, 5.1 %, P = 0.004), accompanied with an increased prevalence of fatty liver among both men (10.8, 26.3, 33.8, 36.7, and 38.0 %, P < 0.001) and women (6.5, 16.7, 22.2, 21.3, and 20.8 %, P < 0.001).

Conclusion

Fatty liver independently predicts both present and future DM. Fatty liver may play an important role in the recent increases in the prevalence of DM.     

Endoscopic ultrasonography-guided transmural drainage of an infected hepatic cyst due to Edwardsiella tarda: a case report

Infected hepatic cysts are very rare compared to simple liver cysts and abscesses. We treated a 77-year-old man with an infected hepatic cyst in the lateral segment caused by Edwardsiella tarda, which has not been previously reported as a pathogenic organism associated with infected hepatic cysts. Percutaneous drainage was temporarily effective, but infection recurred after the drainage tube was removed. We then inserted two drainage tubes into the cyst using an endoscopic ultrasonography (EUS)-guided technique, which was developed from EUS-guided fine needle aspiration (EUS-FNA). The internal drainage tube was a 7 Fr double pigtail stent, and the external tube was a 6 Fr nasobiliary drainage tube. Lavage through the external drainage tube was carried out for one week. The external drainage tube was discontinued when the patient’s condition improved significantly. Sixteen days after tube insertion, he was discharged with the internal tube draining the hepatic cyst into the stomach. Fifteen months after EUS-guided drainage, CT examination showed no recurrence of the hepatic cyst. EUS-guided drainage is an effective treatment for infected hepatic cysts.