The Degree of Disease Knowledge in Patients with Gastroesophageal Reflux Disease: A Multi-center Prospective Study in Korea.

BACKGROUND/AIMS: Patient education has been shown to be beneficial in several diseases. To properly educate patients with gastroesophageal reflux disease (GERD), it is necessary to understand how much they already know about their disease. However, no study has examined the degree of disease knowledge in Korean patients with GERD. Therefore, we conducted this study to assess the degree of knowledge in such patients. METHODS: This multicenter prospective study was conducted from January 2014 to January 2015. A total of 746 patients (mean age, 52 years; 57.6% female) were enrolled from 7 hospitals in Korea. Inclusion criteria were diagnosis of GERD and ability to properly complete a survey. Degree of disease knowledge was assessed using the translated, validated Korean Urnes questionnaire, which consists of 22 items related to GERD. RESULTS: Mean percentage of correct answers was 46.3% and mean GERD knowledge score was 9.6. Degree of knowledge (mean percentage of correct answers) regarding etiology, prognosis, and treatment of GERD were 49.5%, 36.7%, and 37.5%, respectively. Degree of disease knowledge differed significantly according to age (P < 0.001), education (P < 0.001), income (P = 0.028), and occupation (P < 0.001). In multivariate analysis, using multiple logistic regression, the higher knowledge score group tended to have higher education and professional occupation. CONCLUSIONS: The surveyed Korean patients had relatively low disease knowledge, suggesting that a GERD educational program may be beneficial in Korea. Formulation of a program is underway.

α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects.

Extranigral non-motor signs precede the first motor manifestations of Parkinson's disease by many years in some patients. The presence of α-synuclein deposition within colon tissues in patients with Parkinson's disease can aid in identifying early neuropathological changes prior to disease onset. In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon. Twelve subjects undergoing colectomy for primary colon cancer were recruited for this study. Immunohistochemical staining for α-synuclein in normal and phosphorylated forms was performed in normally appearing colonic tissue. We evaluated 16 candidate premotor risk factors in this study cohort. Among them, ten subjects showed positive immunostaining with normal- and phosphorylated-α-synuclein. An accumulation of premotor markers in each subject was accompanied with positive normal- and phosphorylated-α-synuclein immunostaining, ranging from 2 to 7 markers per subject, whereas the absence of Lewy bodies in the colon was associated with relative low numbers of premotor signs. A principal component analysis and a cluster analysis of these premotor markers suggest that urinary symptoms were commonly clustered with deposition of peripheral phosphorylated-α-synuclein. Among other premotor marker, color vision abnormalities were related to non-smoking. This mathematical approach confirmed the clustering of premotor markers in preclinical stage of Parkinson's disease. This is the first report showing that α-synuclein in the colon and other premotor markers are related to each other in neurologically normal subjects.

Gastrointestinal Autonomic Dysfunction in Patients with Parkinson's Disease.

Currently, gastrointestinal dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be an initial symptom in the pathological process that eventually results in PD. Gastrointestinal symptoms may result from the involvement of either the central or enteric nervous systems, or these symptoms may be side effects of antiparkinsonian medications. Weight loss, excessive salivation, dysphagia, nausea/gastroparesis, constipation, and defecation dysfunction all may occur. Increased identification and early detection of these symptoms can result in a significant improvement in the quality of life for PD patients.

[Current issues on gastroesophageal reflux disease].

Gastroesophageal reflux disease (GERD) is one of the most common problems in gastrointestinal disorders. With the increase in our understanding on the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extraesophageal manifestations. This has led to significant confusion regarding the optimal approach to these patients. This article aims to discuss current issues on GERD.

The frequency and severity of gastrointestinal symptoms in patients with early Parkinson's disease.

OBJECTIVE: Although gastrointestinal dysfunctions occur in the majority of patients with Parkinson's disease (PD), they are often unrecognized because many patients remain relatively asymptomatic in the early stage. We investigated the frequency of gastrointestinal symptoms in patients with PD using newly developed gastrointestinal symptom questionnaires. METHODS: Early PD patients with a symptom duration not exceeding 3 years were included in this study. All PD patients were evaluated using a questionnaire, which consisted of three relevant domains: oropharyngoesophageal (10 items); gastric (3 items); and intestinal-anorectal (7 items). The frequency of symptoms was calculated as a proportion with an item score ≥ 2. RESULTS: Of the 54 patients enrolled, 48 patients (88.9%) responded that bowel symptoms developed before the onset of Parkinsonian motor symptoms, and four patients reported that the onset of two types of symptoms (i.e., bowel and neurological) occurred approximately simultaneously, with only months between them. The frequencies of gastrointestinal symptoms are as follows: speech disturbance (40.7%), drooling (24.1%), sense of getting stuck (31.5%), choking (27.8%), globus pharyngis (16.7%), repetitive deglutition (29.6%), pain during swallowing (5.6%), food regurgitation (3.7%), acid reflux (7.4%), nausea/vomiting (11.1%), early satiety (16.7%), postprandial fullness (14.8%), epigastric soreness (9.3%), abdominal pain (3.7%), constipation (46.3%), excessive strain during defecation (33.3%), fecal incontinence (7.4%), tenesmus (20.4%), loose stool or diarrhea (3.7%), and difficulty in relaxing anal sphincter (11.1%). Two patients were scored at zero. CONCLUSIONS: Our findings confirm that gastrointestinal dysfunction occurs in early PD in relatively high frequency.

Acute pancreatitis secondary to ciprofloxacin therapy in patients with infectious colitis.

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.

Fructose Malabsorption in Patients With Irritable Bowel Syndrome-like Symptoms: What Is the Role in the Pathogenesis and Clinical Implication?

Article: Unclear abdominal discomfort: pivotal role of carbohydrate malabsorption Goebel-Stengel M, Stengel A, Schmidtmann M, van der Voort I, Kobelt P, Mönnikes H.

Blockade of visfatin induction by oleanolic acid via disturbing IL-6-TRAF6-NF-κB signaling of adipocytes.

Oleanolic acid is a pentacyclic triterpenoid naturally present in foods and medicinal plants with anticancer, antioxidant, and antiaging properties. The current study elucidated that oleanolic acid inhibited the production of insulin-mimetic and inflammatory adipokine of visfatin during adipogenic differentiation of 3T3-L1 adipocytes. Adipocytes were cultured in an adipogenic media with and without 1-25 µM oleanolic acid up to 8 days for differentiation. The cellular expression and secretion of visfatin was markedly enhanced in differentiating adipocytes, which was dose-dependently attenuated by 1-25 µM oleanolic acid. Secretion of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 was highly elevated during differentiation, which was much earlier than visfatin production of adipocytes. The visfatin production was secondary to inflammatory IL-6 and MIP-2. This study further elucidated that nuclear factor-κB (NF-κB) signaling was responsible for cellular production of visfatin. NF-κB was activated by translocating into the nucleus with increased phosphorylation of inhibitory κB (IκB), which was disturbed by oleanolic acid. Cellular expression of tumor necrosis factor receptor associated factor 6 (TRAF6), a NF-κB upstream, was upregulated in parallel with transactivation with NF-κB. The TRAF6 induction required the auto-stimulation of inflammatory IL-6 and MIP-2. These results demonstrate that oleanolic acid inhibited visfatin and its inflammatory response during adipocyte differentiation through blocking IL-6-TRAF6-NF-κB signaling. Therefore, oleanolic acid may be a potent therapeutic agent targeting against adipogenesis and visfatin-linked inflammation.

Oleanolic acid suppresses resistin induction in adipocytes by modulating Tyk-STAT signaling.

Oleanolic acid, a naturally occurring triterpenoid widely distributed in foods and medicinal plants, has anticancer, antioxidant, and antiaging properties. We hypothesized that oleanolic acid would suppress the production of the inflammatory adipokine resistin during adipogenic differentiation of 3T3-L1 adipocytes. 3T3-L1 adipocytes were cultured in adipogenic media with and without 1 to 25 µM oleanolic acid for up to 8 days to stimulate adipocyte differentiation. Adipocyte production of resistin was markedly enhanced during differentiation and was dose dependently attenuated by 1 to 25 µM oleanolic acid. This study further investigated whether Tyk2-Stat1/3 signaling was responsible for cellular production of resistin. Signal transducer and activator of transcription factor (STAT) 1 and STAT3 were activated during differentiation in a disparate temporal fashion; STAT1 was maximally phosphorylated on day 5 after initiating differentiation, whereas STAT3 was rapidly activated within 1 day of differentiation. When oleanolic acid was supplied to differentiating adipocytes, STAT1 and STAT3 phosphorylation was substantially suppressed. Upstream Tyk2 was rapidly activated in a manner similar to STAT3 and reactivated on days 3 to 5 after initiating differentiation, which was attenuated by incubating adipocytes with oleanolic acid. In addition, cellular expression of suppressor of cytokine signaling 3 (SOCS3), which inhibits Tyk2 activity, was markedly promoted from day 5 of adipocyte differentiation. Oleanolic acid attenuated SOCS3 expression, which was highly enhanced during the late phase of differentiation. Taken together, oleanolic acid suppressed adipocyte differentiation-associated resistin and adipogenesis production by disturbing the Tyk2-STAT1/3 signaling pathway and promoting SOCS3 expression. Therefore, oleanolic acid may be a possible bioactive agent that blunts adipogenesis and adipokine inflammation.

Anorectal manometric dysfunctions in newly diagnosed, early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. METHODS: We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. RESULTS: Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. CONCLUSIONS: These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD.

Long-term prognosis of an endoscopically treated rectal neuroendocrine tumor: 10-year experience in a single institution.

BACKGROUND AND AIM: The endoscopic techniques for treating a small rectal neuroendocrine tumor (NET) are performed in most large centers; however, the endoscopic management of this condition is not well established. This study was designed to determine the long-term prognosis of endoscopically resected NET. METHODS: We prospectively studied patients with endoscopically treated rectal NET in Seoul St Mary's hospital, between January 2000 and June 2010. The long-term outcomes were analyzed in association with the pathological complete resection and resection procedures. RESULTS: Seventy-seven patients (48 men and 29 women; mean age, 52.3 years; range, 23-77 years) were included. The average NET size was 7.0±2.8 mm (range, 3-16 mm). There was no procedure-related complication. En-bloc removal was achieved for all lesions, and the rate of histological complete resection was 75.3% (58/77). Histological complete resection rates were 71.4% (10/14) by conventional endoscopic mucosal resection (EMR), 74.1% (43/58) by a two-channel EMR, and 100.0% (5/5) by endoscopic submucosal dissection (ESD). Among six patients with incomplete histological resection, two underwent additional EMR, two underwent transanal endoscopic microsurgery, and two underwent low anterior section with lymph node dissection. The remaining 13 patients with 'possible' remnant NET underwent regular endoscopic surveillance without additional resection. In the latter group, only one patient had local recurrence, detected on regular colonoscopic surveillance, after 56 months and was treated with additional EMR. All of the patients are alive and 98.7% (76/77) of the patients are free from disease during the follow-up periods. CONCLUSION: Endoscopic resection is a safe and effective modality and may potentially be used for the treatment of NETs smaller than 15 mm in diameter, those confined to the submucosal layer, and those without metastasis. Local treatment was believed to be curative in cases with complete histological resection. In addition, this treatment may have an excellent prognosis in patients with 'possible' remnant NET.

Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer.

OBJECTIVES: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer (PC). METHODS: Patients with PC TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the nonperfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. RESULTS: High-intensity focused ultrasound treatment was performed without severe adverse event in 46 patients, 49 times (male-female = 25:21; mean age, 60.7 ± 10.0; TNM stage 3-stage 4 = 18:28). Average size of the PC lesion was 4.2 ± 1.4 cm (1.6-9.3 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 38 lesions, 90% to 50% in 8, and within 50% in 3. Overall median survival (S1) from initial PC diagnosis was 12.4 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 52.2%, 30.4%, and 21.79%, respectively, with a median survival of 7.0 months CONCLUSIONS: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced PC.

Numb chin syndrome with concomitant painful ophthalmoplegia leading to a diagnosis of diffuse large B cell lymphoma.

Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease.

Clinical features of abdominal actinomycosis: a 15-year experience of a single institute.

This study was designed to evaluate the clinical features of abdominal actinomycosis and to assess its therapeutic outcome. We reviewed patients with abdominal actinomycosis in Seoul St. Mary hospital, between January 1994 and January 2010. Twenty-three patients (5 male and 18 female, mean age, 47.8 yr; range, 6-75 yr), with abdominal actinomycosis were included. Emergency surgery was performed in 50% due to symptoms of peritonitis. The common presentation on preoperative computerized tomography was a mass with abscess, mimicking malignancy. The mean tumor size was 7.0 cm (range, 2.5-10.5). In all patients, actinomycotic masses were surgically removed. Mean duration of hospital stay was 17.8 days (range, 5-49). Long term oral antibiotic treatment (mean 4.2 months; range, 0.5-7.0 months) were administered to all patients. All patients were free of recurrence after a median follow up of 30.0 months (mean 35.5 ± 14.8 months, range, 10.0-70.0 months); recurrence was not seen in any patient. In conclusion, abdominal actinomycosis should be included as a differential diagnosis when an unusual abdominal mass or abscess presents on abdominal CT. Assertive removal of necrotic tissue with surgical drainage and long term antibiotic treatment provide a good prognosis in patients with actinomycosis.

Anorectal dysfunctions in Parkinson's disease.

Anorectal symptoms are frequently found in patients with Parkinson's disease (PD), mainly manifested as diffuse lower abdominal discomfort, constipation, and fecal incontinence. Among these symptoms, constipation may precede by years the motor manifestations of PD. Research has focused for decades on selection of a measurement method for detection of abnormalities and support of clinometric instruments for anorectal symptoms. We review those manifestations and their contribution to evaluation of the anorectal symptoms in patients with PD.

Oleanolic acid reduces markers of differentiation in 3T3-L1 adipocytes.

Oleanolic acid is a triterpenoid compound that is widely present in vegetables, medicinal herbs, and other plants and has potent antioxidant and antiinflammatory properties. However, the potential of oleanolic acid to offset obesity is not clear. This study tested the hypothesis that oleanolic acid suppresses the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of peroxisome proliferators-activated receptor γ (PPARγ) and cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein α (C/EBPα). The 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium containing 10% fetal bovine serum for 6 to 8 days in the absence and presence of 1 to 25 µmol/L oleanolic acid according to differentiating protocols. Nontoxic oleanolic acid, at 25 µmol/L or less, dose-dependently attenuated lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. Western blot analysis showed that the induction of PPARγ and C/EBPα was markedly attenuated in differentiated and oleanolic acid-treated adipocytes at their transcriptional messenger RNA levels. Furthermore, this study examined whether oleanolic acid dampened the induction of visfatin, a proinflammatory and visceral fat-specific adipokine expressed in adipocytes. Visfatin expression was inhibited in differentiated adipocytes exposed to a PPARγ inhibitor GW9662. In addition, the visfatin production was significantly repressed in 25 µmol/L oleanolic acid-treated adipocytes, possibly through blocking PPARγ activation. These results demonstrate that oleanolic acid may be a promising agent to disturb adipocyte differentiation and suppress obesity-associated inflammation.

Novel Danshen methoxybenzo[b]furan derivative antagonizing adipogenic differentiation and production of inflammatory adipokines.

Many benzo[b]furan lignans are known to be biologically active in nature. 2-(3'-Methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan-3-carbaldehyde (XH-14) is found as a bioactive component isolated from the plant Salvia miltiorrhiza, commonly known as Danshen, which is a traditional Chinese medicine that is used as a cardiovascular medication. This study examined whether 3 different XH-14 derivatives can inhibit adipocyte differentiation and induction of the adipokines visfatin and resistin in 3T3-L1 adipocytes. Adipocytes were cultured and differentiated in Dulbecco's modified Eagle medium containing fetal bovine serum, 3-isobytyl-1-methylxanthine, dexamethasone, and insulin for 6-8d in the absence and presence of 1-25µM XH-14-derived benzo[b]furan derivatives. Nontoxic 2-(3'-methoxy-4'-hydroxy-phenyl)-6-(3-hydroxypropyl)-5-methoxy-benzo[b]furan (5-MBF) at ≥5µM attenuated cellular lipid accumulation and down-regulated induction of peroxisome proliferator activated receptors γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) in a dose-dependent manner, as evidenced by Oil Red O staining and Western blot analysis. Such inhibition of PPAR( and C/EBP( by 5-MBF was achieved at transcriptional mRNA levels. However, 2-(3'-methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan (7-MBF) and 2-(3'-methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan (6-MBF) had minimal effects on adipogenic differentiation, suggesting a structure-activity relationship of methoxybenzo[b]furan derivatives as an inhibitor of adipogenic differentiation. Furthermore, ≥5µM 5-MBF retarded protein and mRNA expression of proinflammatory and insulin resistance-enhancing adipokines of visfatin and resistin in differentiated adipocytes. Induction of visfatin and resistin was, at least in part, mediated via adipocyte differentiation-associated activation of PPARγ signal targeting adipocyte protein 2 and stearoyl-CoA desaturase. These results demonstrate that the 2-(3'-methoxy-4'-hydroxy-phenyl)-3-hydroxypropyl benzo[b]furan lignan, with a methoxy group at the 5-position on the benzene ring, may be a promising agent for disturbance of adipogenic differentiation and for blockage of obesity-associated inflammatory and metabolic diseases.

Role of (-)-epigallocatechin-3-gallate in cell viability, lipogenesis, and retinol-binding protein 4 expression in adipocytes.

(-)-Epigallocatechin-3-gallate (EGCG), a bioactive compound of green tea, is known to combat obesity by reducing the viability and lipid accumulation of adipocytes. In this study, we evaluated the mechanism and clinical relevance on those actions of EGCG. We measured the viability of 3T3-L1 preadipocytes and adipocytes by the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide assay. Lipid accumulation was measured by Oil Red O staining. Intracellular accumulation of reactive oxygen species (ROS) was determined using a flow cytometer. Cellular glucose uptake was determined with 2-deoxy-[(3)H]-glucose. The protein levels of peroxisome proliferator-activated receptor (PPAR)-γ and adiponectin in 3T3-L1 adipocytes, as well as the protein level and secretion of plasma retinol-binding protein (RBP4) in human adipocytes, were measured by western blot. EGCG at concentrations higher than 10 µM induced ROS generation and decreased the viability and lipid accumulation of adipocytes. It also decreased the expression of PPAR-γ and adiponectin. At concentrations readily achievable in human plasma via green tea intake (≤10 µM), EGCG inhibited cellular glucose uptake and enhanced the expression and secretion of RBP4 in adipocytes. Pharmacological doses of EGCG showed cytotoxic effects in preadipocytes and adipocytes. EGCG-mediated glucose uptake inhibition in adipocytes may be clinically relevant and is probably linked to the increase in the expression and secretion of RBP4. Because secreted RBP4 from adipocytes inhibits muscular glucose uptake and enhance hepatic glucose output, the systemic effect of EGCG associated with its effect on RBP4 secretion should be further determined, as it may negatively regulate whole-body insulin sensitivity, contrary to general belief.

The prevalence and patterns of pharyngoesophageal dysmotility in patients with early stage Parkinson's disease.

Dysphagia occurs in the majority of patients with Parkinson's disease (PD) and is known to correlate with abnormalities of oropharyngeal function. The aim of this study was to evaluate pharyngoesophageal activity in patients with early-stage PD. Newly diagnosed PD patients with a symptom duration not exceeding 3 years were included. All PD patients were questioned about symptoms of dysphagia and underwent combined multichannel intraluminal impedance manometry and multiple rapid swallow tests. Fifty-four patients (22 men and 32 women, 67.1 ± 10.3 years) were enrolled. The duration of Parkinsonian motor symptoms was 11.5 ± 8.8 months, the Hoehn and Yahr stage was 1.6 ± 0.4, and the total Unified Parkinson's Disease Rating Scale was 25.1 ± 18.6. Esophageal manometry in the liquid swallow and viscous swallow tests was abnormal in 22 (40.7%) and 31 (67.4%) patients, respectively. Although manometric abnormalities were more common in patients with more severe dysphagia symptoms, many patients with no or minimal symptoms also had manometric abnormalities. Repetitive deglutition significantly correlated with failed peristalsis and incomplete bolus transit. Abnormal responses to multiple rapid swallow tests were found in 33 out of 54 patients; 29 with incomplete inhibition (repetitive contraction) and 4 with failed peristalsis. These results suggest that the majority of patients with early-stage PD showed pharyngeal and esophageal dysfunction even before clinical manifestations of dysphagia, which may reflect selective involvement of either the brain stem or the esophageal myenteric plexus in early-stage PD.

Suppression of colonic aberrant crypt foci by soy isoflavones is dose-independent in dimethylhydrazine-treated rats.

The potential of soy isoflavones (SIs) to reduce colon cancer has been investigated in animal models. These studies have found that outcomes are variable and depend on SI dose. The present study investigated dose-response effects of SIs on colon carcinogenesis in a chemically induced rat cancer model. Sprague-Dawley male rats were injected with 1,2-dimethylhydrazine (DMH) and were provided experimental diets that contained 0, 10, 50, 150, or 500 mg of SI aglycones/kg of diet for 12 weeks. Plasma concentrations of genistein, daidzein, and equol were determined using time-resolved fluoroimmunoassay. Plasma concentrations of these SIs tended to increase in a dose-dependent manner in DMH-treated rats. The numbers of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) proteins of colons were significantly decreased in the SI-fed groups compared with the control group; however, suppression was not dose-dependent. Furthermore, there were no significant correlations between plasma SI concentrations and ACF or COX-2 expression. Increased SI intake and increased plasma levels of SIs and metabolites were not associated with tissue levels of lipid peroxidation. We conclude that dietary supplementation of SIs suppresses DMH-induced ACF formation and COX-2 expression in a dose-independent manner.