Comparison of Two Types of Electrodes for Measuring Submental Muscle Activity During Swallowing.

PURPOSE: This study aimed to investigate the potential of a newly developed small electrode to accurately record muscle activity during swallowing. MATERIAL AND METHODS: This study included 31 healthy participants. The participants underwent swallowing trials with three types of material. The recordings involved the following conditions: 1) swallowing saliva, 2) swallowing 3 mL water, and 3) swallowing 5 mL water. Two types of electrodes, a conventional electrode (CE) and a newly developed small electrode (NE), were symmetrically positioned on the skin over the suprahyoid muscle group, starting from the center. From the surface electromyography data, the swallowing duration (s), peak amplitude, and rising time (duration from swallowing onset to peak amplitude: s) were measured. Additionally, the equivalence of characteristics of the waveform of muscle activities was calculated by using the variance in both the upper and lower confidence limits in duration and rising time. RESULTS: No significant differences in baseline, swallowing duration or rising time between the CE and NE were observed for any swallowing material. The peak amplitude was significantly higher for the NE than for the CE for all swallowing materials. The CE and NE displayed no significant difference in the equivalence of characteristics of the waveform of muscle activities for any swallowing material. CONCLUSIONS: The gold-plated small electrodes utilized in this study indicated the ability to record the same characteristics of muscle activity as conventional electrodes. Moreover, it was able to capture the muscle activity of each muscle group with improved sensitivity in a narrow area, such as under the submandibular region, with more precision than that of conventional electrodes.

Involvement of Muscarinic M3 Receptor in the Development of M2 Macrophages in Allergic Inflammation.

INTRODUCTION: The muscarinic M3 receptor antagonist, tiotropium, has a bronchodilatory effect on asthma patients. Additionally, tiotropium inhibits allergic airway inflammation and remodeling in a murine asthma model. However, the underlying mechanisms of this M3 receptor antagonist remain unclear. Therefore, we investigated the effect of muscarinic M3 receptor blockage on M2 macrophage development during allergic airway inflammation. METHODS: BALB/c mice were sensitized and challenged with ovalbumin to develop a murine model of allergic airway inflammation mimicking human atopic asthma. During the challenge phase, mice were treated with or without tiotropium. Lung cells were isolated 24 h after the last treatment and gated using CD68-positive cells. Relm-α and Arginase-1 (Arg1) (M2 macrophage markers) expression was determined by flow cytometry. Mouse bone marrow mononuclear cell-derived macrophages (mBMMacs) and human peripheral blood mononuclear cells (PBMCs)-derived macrophages were stimulated with IL-4 and treated with a muscarinic M3 receptor antagonist in vitro. RESULTS: The total cells, eosinophils, and IL-5 and IL-13 levels in BAL fluids were markedly decreased in the asthma group treated with tiotropium compared to that in the untreated asthma group. The Relm-α and Arg1 expression in macrophages was reduced considerably in the asthma group treated with tiotropium compared to that in the untreated asthma group, suggesting that the development of M2 macrophages was inhibited by muscarinic M3 receptor blockage. Additionally, muscarinic M3 receptor blockage in vitro significantly inhibited M2 macrophage development in both mBMMacs- and PBMCs-derived macrophages. CONCLUSIONS: Muscarinic M3 receptor blockage inhibits M2 macrophage development and prevents allergic airway inflammation. Moreover, muscarinic M3 receptors might be involved in the differentiation of immature macrophages into M2 macrophages.

Relationships between Lip Seal Strength, Tongue Pressure, and Daytime Sleepiness in Japanese Workers: A Cross-Sectional Study.

This cross-sectional study aimed to examine the relationships between lip seal strength, tongue pressure, and daytime sleepiness in Japanese workers. A self-administered questionnaire which comprised the Epworth Sleepiness Scale (ESS) was completed by 496 workers, and excessive daytime sleepiness was defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. The median ESS score was 5.0 (25th and 75th percentiles: 2.0 and 8.0), and 42 (8.5%) workers had excessive daytime sleepiness. The median lip seal strength was 13.5 N (11.4, 16.3), and the tongue pressure was 41.7 kPa (35.2, 48.3). Workers with higher ESS scores had significantly lower levels of lip seal strength than those without, following adjustments for age and body mass index (BMI) values (ß (95% confidence interval): -0.043 [-0.081, -0.004]). However, tongue pressure was not significantly associated with ESS score after adjustments for age and/or BMI. These results suggest that maintaining moderate lip seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.

Lip Seal Strength and Tongue Pressure among Japanese Male Workers: Comparison of Different Age Groups.

Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.

Correlation of Arterial CO2 and Respiratory Impedance Values among Subjects with COPD.

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student's t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.

Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD.

Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide.

BACKGROUND: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD's usefulness if taken after a virus has already infected airway tissue. OBJECTIVE: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD's experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. CONCLUSION: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. CONCLUSION: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma.

PURPOSE: Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma. METHODS: Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed. RESULTS: OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA. CONCLUSIONS: These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

The incidence and outcome of allied disorders of Hirschsprung's disease in Japan: Results from a nationwide survey.

BACKGROUND: Allied disorders of Hirschsprung's disease (ADHD) have been proposed to be the concept of the functional obstruction of the intestine with the presence of ganglion cells in the terminal rectum. They are classified into two categories based on pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis (HG), and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation (SD), internal anal sphincter achalasia (IASA), and chronic idiopathic intestinal pseudo-obstruction (CIIP). Some of these show poor prognosis, therefore, the establishment of criteria and appropriate treatment strategies is required. METHODS: The questionnaires were sent to the 161 major institutes of pediatric surgery or gastroenterology in Japan, in order to collect the cases of ADHD during 10 years from 2001 and 2010. RESULTS: In total, 355 cases were collected. They included 28 immaturity of ganglia, 130 HG (121 congenital, 9 acquired), 18 intestinal neuronal dysplasia, 33 MMIHS, 43 SD, three IASA, and 100 CIIP. Of the 95 institutes, 69 (72.6%) had their own criteria for ADHD. Criteria were based on clinical symptoms and signs, and conventional pathological examinations. Prognosis was poor in congenital HG, MMIHS, and CIIP, while the others showed good survival rates. CONCLUSION: Almost all Japanese cases of ADHD in the past 10 years were collected. Congenital HG and CIIP showed relatively high incidence, whereas acquired HG and IASA were extremely rare in Japan. The criteria of each disorder were also collected and summarized. Prognosis was poor in congenital HG, MMIHS, and CIIP.

Evaluation of the association between sensitization to common inhalant fungi and poor asthma control.

BACKGROUND: Fungi are well-known airborne allergens that are predisposing environmental factors to asthma. Few comparative studies have evaluated sensitization to common inhalant fungi in relation to poor asthma control in patients with asthma. OBJECTIVE: To evaluate the association between sensitization to individual fungi and asthma control and elucidate the characteristics of patients with poorly controlled asthma sensitized to fungi. METHODS: This cross-sectional study was performed at Showa University Hospital between September 2014 and December 2014. The specific IgE levels for several major aeroallergens, including house dust mites, Japanese cedar, various types of pollen, furry animals, or insects, were measured with a fluorescent enzyme immunoassay in 160 patients with adult asthma. RESULTS: Fungal sensitization was predominant in men with asthma, and it was associated with poor asthma control. Sensitization to house dust mites, Japanese cedar, pollen, furry animals, or insects was not associated with poor asthma control. Logistic regression analyses revealed that patients sensitized to Aspergillus and Penicillium had a significantly increased risk of poor asthma control. More Penicillium IgE-positive patients were men and pet owners compared with Penicillium IgE-negative patients; in addition, Penicillium IgE-positive patients had higher total IgE levels. The Asthma Control Test level was significantly higher in Penicillium IgE-positive patients than in Penicillium IgE-negative patients. However, there were no differences in fractional exhaled nitric oxide, forced vital capacity, and forced expiratory volume in 1 second. Finally, sensitization to Aspergillus, Cladosporium, and Trichophyton were positively correlated with sensitization to Penicillium. CONCLUSION: Sensitization to fungi is predominant in men, and it is associated with poor asthma control. In particular, sensitization to Penicillium and Aspergillus is a risk factor for asthma severity. These results have potential relevance in asthma management.

[Treatment Strategy for Acute Type B Aortic Dissection with End-organ Malperfusion].

Therapeutic strategies for treating Stanford type B dissection with endo-organ malperfusion remain controversial, and whether surgery or conservative treatment should be performed is a matter of ongoing debate. In this study, we examined the treatment strategies used in cases of malperfusion in which treatment was initiated conservatively at the onset of symptoms without superior mesenteric artery (SMA) or limb artery obstruction. A total of 16 patients had organ ischemia in this series. The obstructed branches were the SMA in 5 patients, the artery of Adamkiewicz in 2, the bilateral renal arteries in 3, the celiac artery in 3 and limb arteries in 3. The surgical procedure included bypass grafting in 2 patients with SMA obstruction and extra-anatomical bypass in 2 patients with limb artery obstruction. A total of 11 patients were treated without surgery. Three patients died, including 2 patients with SMA obstruction. The remaining patient who died had limb artery obstruction and did not undergo surgery. The results suggest that patients with acute type B aortic dissection with endo-organ malperfusion who develop SMA or limb artery obstruction require early surgery.

Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.

Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose < 200) and 27% developed severe hyperglycemia (blood glucose ≥ 600). Hyperglycemia was associated with increased inflammation and reduced insulin secretion and sensitivity compared with control mice or CLP mice maintaining euglycemia. Insulin prevented the progression to severe hyperglycemia but was ineffective in reestablishing glycemic control once hyperglycemia had developed. In conclusion, early initiation of clinically relevant low-level dextrose (∼ 20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.

Incidence of contralateral patent processus vaginalis in relation to age at laparoscopic percutaneous extraperitoneal closure for pediatric inguinal hernia.

INTRODUCTION: Laparoscopic percutaneous extraperitoneal closure (LPEC) allows the surgeon to look for contralateral patent processus vaginalis (CPPV) directly. We investigated the incidence of CPPV in relation to age at LPEC. METHODS: Following Institutional Review Board approval, 1232 patients ranging in age from 2 months old to 15 years old (median 4.7 years), who underwent LPEC, were investigated retrospectively. Patients were divided into five groups based on their age at surgery: younger than 1, 1-2, 2-4, 4-6 years, and older than 6 years. The incidence of CPPV being detected by preoperative ultrasonography or laparoscopy was compared among these groups. Statistical analyses were performed using the Chi-square test or Cochran-Armitage trend test, and p < 0.05 was considered significant. RESULTS: The incidence of CPPV detected by ultrasonography decreased as the age increased (p < 0.0001), whereas the incidence of CPPV newly revealed by laparoscopy increased as age increased (p = 0.0001). There were no significant differences in the incidence of CPPV in patients with unilateral hernia among the five age groups (p = 0.74). CONCLUSIONS: These results showed that the incidence of CPPV in patients with unilateral inguinal hernia did not change in relation to their age.

Effects of insistent screening for contralateral patent processus vaginalis in laparoscopic percutaneous extraperitoneal closure to prevent metachronous contralateral onset of pediatric inguinal hernia.

PURPOSE: Laparoscopic percutaneous extraperitoneal closure (LPEC) is known to reduce the incidence of metachronous contralateral hernia (MCH) compared to conventional hernia repair. We herein describe the effects of insistent screening for an irregular orifice of the contralateral patent processus vaginalis (CPPV). METHODS: All patients who underwent LPEC between 2003 and 2013 were reviewed. We started insistent screening for a CPPV in July 2010. The surgically treated cases before June 2010 were assigned to the former group, while those treated after July 2010 were in the latter group. The data were retrospectively collected from medical records. The statistical analysis was performed using the Mann-Whitney U test or Chi square test. A value of P < 0.05 was considered to be significant. RESULT: A total of 1113 patients (514 males and 599 females) ranging in age from 3 months old to 15 years old (median 4.6 years old), were reviewed. Of the 626 patients in the former group, a CPPV was detected in 227 patients. Of the 487 patients in the latter group, a CPPV was detected in 271 patients. The incidence of a CPPV significantly increased over time (P < 0.001). We encountered five cases of MCH, all of which belonged to the former group (P = 0.048). CONCLUSIONS: The increased detection of a CPPV by insistent screening seemed to cause a decrease in the incidence of MCH.

Identification of natural inhibitors of Entamoeba histolytica cysteine synthase from microbial secondary metabolites.

Amebiasis is a common worldwide diarrheal disease, caused by the protozoan parasite, Entamoeba histolytica. Metronidazole has been a drug of choice against amebiasis for decades despite its known side effects and low efficacy against asymptomatic cyst carriers. E. histolytica is also capable of surviving sub-therapeutic levels of metronidazole in vitro. Novel drugs with different mode of action are therefore urgently needed. The sulfur assimilatory de novo L-cysteine biosynthetic pathway is essential for various cellular activities, including the proliferation and anti-oxidative defense of E. histolytica. Since the pathway, consisting of two reactions catalyzed by serine acetyltransferase (SAT) and cysteine synthase (CS, O-acetylserine sulfhydrylase), does not exist in humans, it is a rational drug target against amebiasis. To discover inhibitors against the CS of E. histolytica (EhCS), the compounds of Kitasato Natural Products Library were screened against two recombinant CS isozymes: EhCS1 and EhCS3. Nine compounds inhibited EhCS1 and EhCS3 with IC50 values of 0.31-490 µM. Of those, seven compounds share a naphthoquinone moiety, indicating the structural importance of the moiety for binding to the active site of EhCS1 and EhCS3. We further screened >9,000 microbial broths for CS inhibition and purified two compounds, xanthofulvin and exophillic acid from fungal broths. Xanthofulvin inhibited EhCS1 and EhCS3. Exophillic acid showed high selectivity against EhCS1, but exhibited no inhibition against EhCS3. In vitro anti-amebic activity of the 11 EhCS inhibitors was also examined. Deacetylkinamycin C and nanaomycin A showed more potent amebicidal activity with IC50 values of 18 and 0.8 µM, respectively, in the cysteine deprived conditions. The differential sensitivity of trophozoites against deacetylkinamycin C in the presence or absence of L-cysteine in the medium and the IC50 values against EhCS suggest the amebicidal effect of deacetylkinamycin C is due to CS inhibition.