Gastric emptying time and the effect of cisapride in cirrhotic patients with autonomic neuropathy

GOALS To investigate the relationships between gastric emptying and autonomic dysfunction in hepatic cirrhosis and to assess the effects of cisapride on gastric emptying in cirrhotic patients.STUDY Twenty-four cirrhotic patients (8 patients in each Child-Pugh classification) and 25 healthy controls were enrolled. All the patients had viral (B or C) hepatitis. Patients with DM, alcoholic cirrhosis, active peptic ulcer, gastric malignancy and pyloric obstruction were excluded by esophagogastroduodenoscopy. Parasympathetic and sympathetic functions were assessed by the criteria set forth by Ewing and Clark. Drugs affecting GI motility and smoking were discontinued 48 hours and 12 hours prior to the study respectively. A solid-phase of gastric emptying study was conducted by scintigraphic method for the calculation of gastric half-emptying time (GET1/2). RESULTS The study revealed that 9 patients with Child-Pugh B and C cirrhosis had autonomic neuropathy and none of Child-Pugh A cirrhosis had autonomic neuropathy. Prolonged GET1/2 was noted in cirrhotics compared with the control group (p < 0.05). However, there was significant difference between 9 patients (Child B-C) with autonomic neuropathy compared with patients 15 patients without autonomic neuropathy. Again there was a significant difference in GET1/2 between Child A cirrhotic and Child B-C cirrhotic whether they had autonomic neuropathy or not. Cisapride decreased GET1/2 significantly in cirrhotic patients (Child B-C cirrhotic). Clearly, patients with autonomic neuropathy in Child B-C cirrhosis had significantly reduced GET1/2 after cisapride administration. Even though cisapride decreased GET1/2 in patients with Child B-C cirrhosis without autonomic neuropathy, this was not significant. CONCLUSION Autonomic neuropathy in advanced cirrhosis from viral hepatitis may cause prolonged gastric emptying. Cisapride can shorten gastric emptying time in such patients.     

Relationship of symptoms to lung function abnormalities in preterm infants at follow-up.

Recurrent respiratory symptoms are common in preterm infants in the first 2 years of life. The aim of this study was to determine the lung function abnormalities associated with such symptoms. Forty preterm infants, with a median gestational age of 29 weeks were studied at a median postnatal age of 12 months. Twenty-two suffered from recurrent symptoms, defined as wheezing and/or coughing on at least 4 days per week over the previous month. Lung function was assessed by measurement of functional residual capacity (FRC), using a helium gas dilution technique, and airway resistance (Raw) and thoracic gas volume (TGV) plethysmographically. No significant difference was found in TGV between symptomatic and asymptomatic infants, but the median FRC was lower (P less than 0.01), Raw higher (P less than 0.01), and FRC:TGV ratio lower (P less than 0.001) in the symptomatic infants. These lung function abnormalities in the symptomatic infants are suggestive of gas trapping.     

Serum positive cagA in patients with non-ulcer dyspepsia and peptic ulcer disease from two centers in different regions of Turkey

AIM: To investigate and compare frequencies of serum positive cagA in patients from two separate regions of Turkey who were grouped according to the presence of peptic ulcer disease or non-ulcer dyspepsia. METHODS: One hundred and eighty Helicobacter pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia were included in the study. One hundred and fourteen patients had non-ulcer dyspepsia and 66 had peptic ulcer disease (32 with gastric ulcers and/or erosions and 34 with duodenal ulcers). Each patient was tested for serum antibody to H. pylori cagA protein by enzyme immunoassay. RESULTS: The total frequency of serum positive cagA in the study group was 97.2 %. The rates in the patients with peptic ulcers and in those with non-ulcer dyspepsia were 100 % and 95.6 %, respectively. These results were similar to those reported in Asian studies, but higher than those that have been noted in other studies from Turkey and Western countries. CONCLUSION: The high rates of serum positive cagA in these patients with peptic ulcer disease and non-ulcer dyspepsia were similar to results reported in Asia. The fact that there was high seroum prevalence regardless of ulcer status suggests that factors other than cagA might be responsible for ulceration or other types of severe pathology in H. pylori-positive individuals.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).     

Colonoscopy in patients with psoriasis before the initiation of treatment with biological agents

Psoriasis may lead to subsequent colorectal cancer, since chronic systemic inflammation is the common etiologic factor in both psoriasis and colorectal cancer. It is a matter of dispute whether biological agents used in the treatment of psoriasis cause predisposition to colorectal cancer as a result of their immunosuppressive effect. Medical records of psoriasis patients who underwent colonoscopy before biological agents were reviewed. Colonoscopy was performed in all patients who were aged 50 years and older and in patients younger than 50, if they had positive fecal occult blood test results. The study included 95 patients between the age of 34 to 84. Colonoscopy results revealed tubular adenoma in 16 (16.8%) patients, hyperplastic polyps in 7 (7.4%) patients, villous adenoma in 1 (1.1%) patient, and tubulovillous adenoma in 1 (1.1%) patient. Two patients were diagnosed with colon cancer detected by a former colonoscopy, which was recommended by their dermatologist before the biological agent treatment plan. These results revealed that adenomatous polyps which can evolve to colon adenocarcinoma were the most frequent polyp type in patients with psoriasis. We suggest that routine colonoscopy should be performed before the initiation of biological therapy in psoriasis patients who are aged 50 years old and over.     

A new classification for septal perforation and effects of treatment methods on quality of life

IntroductionSeptal perforation is a condition characterized by loss of cartilage and/or bony structures along with the mucoperichondrium and mucoperiosteum lining them. The etiology includes a history of nasal surgery or trauma, nose picking, bilateral septal cauterization, overuse of nasal sprays, cocaine abuse, vasculitis, and malignancies.ObjectiveComparison of quality of life in patients with septal perforation after conservative or surgical treatment, and a new approach for the determination of the diameter of the perforation from a different point of view.MethodsThe diameter of septal perforation, total vertical diameter of septum, and horizontal diameter of the perforation were measured in a total of 34 patients. Nineteen of the patients underwent surgical septal perforation repair, and 15 of them received septal button application. The patients were asked to complete the Glasgow Benefit Inventory quality of life questionnaire.ResultsThe septal perforation successfully healed in 18 of 19 patients who underwent surgical treatment. The quality of life scores were statistically significantly higher in the surgical treatment group when compared to the button group (p < 0.05).ConclusionThe septal perforation classification we propose would be beneficial for providing realistic dimensions, treatment methods, and surgical techniques.     

A Novel System to Study the Impact of Epithelial Barriers on Cellular Metabolism

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O₂)₂ 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm² for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society. PAC00: 8716Uv, 8715Vv     

Microsatellite instability is not a common feature in medullary breast cancer

Microsatellite instability (MSI) is a form of genomic instability associated with defective DNA mismatch repair in tumors. MSI is found in 85-90% of hereditary nonpolyposis colorectal cancer cases; however, its occurrence in breast carcinogenesis still remains to be clarified. In addition, data are limited on the incidence of MSI in the medullary subtype. The purpose of this study was to investigate the occurrence of MSI in medullary breast cancer (MBC). The study included a total of 16 patients with MBC, nine with typical and seven with atypical histology. The incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) was determined by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. All 16 tumors showed stability at five loci. Although the number of microsatellite markers and DNA samples may limit the value of our results, we conclude that the MSI phenotype is uncommon in human MBC.