Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa.

BACKGROUND/OBJECTIVES: Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. SUBJECTS/METHODS: We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. RESULTS: Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. CONCLUSION: Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.

Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing PPI responsiveness in patients with GERD.

A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus.NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.

Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats.

PURPOSE: Chronic intermittent hypoxia (IH) plays a pivotal role in the consequences of obstructive sleep apnea (OSA). It has been demonstrated that IH impairs nasomaxillary complex growth to reduce nasal airway cavity size in rodent models. Although turbinate dysfunction with inflammatory mucosal hypertrophy is related to OSA, the role of IH in turbinate hypertrophy with inflammation-driven fibrosis is unknown. Here, we aimed to clarify the pathogenesis of inflammatory mucosal hypertrophy and epithelial-mesenchymal transition (EMT) in the nasal turbinate under IH. METHODS: Seven-week-old male Sprague-Dawley rats were exposed to IH (4% O2 to 21% O2 with 0% CO2) at a rate of 20 cycles/h. RESULTS: Hypertrophy of the turbinate mucosa occurred after 3 weeks, with the turbinate mucosa of the experimental group becoming significantly thicker than in the control group. Immunostaining showed that IH increased the expression of TGFß and N-cadherin and decreased E-cadherin expression in the turbinate mucosa. Quantitative PCR analysis demonstrated that IH enhanced the expression of not only the inflammatory markers Tnf-a, Il-1b, and Nos2 but also the EMT markers Tgf-b1, Col1a1, and Postn. CONCLUSIONS: Collectively, these results suggest that IH induced turbinate hypertrophy via upregulation of gene expression related to inflammation and EMT in the nasal mucosa.

Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.

BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation. SUMMARY: TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.

Zinc deficits, mucositis, and mucosal macrophage perturbation: is there a relationship?

PURPOSE OF REVIEW: Mucositis is a common and therapy-limiting adverse effect of cancer treatments including radiotherapy, chemotherapy, and immunotherapy. The optimal zinc formulation, dosage, and timing of administration warrant further research as does the efficacious prevention of febrile mucositis that predisposes to febrile neutropenia. RECENT FINDINGS: Metaanalyses concluded that zinc sulfate failed to significantly reduce the incidence or severity of chemotherapy-induced oral mucositis, whereas polaprezinc was associated with a significant reduction. Three new trials were published in 2018. The first trial found that zinc sulfate reduced the incidence and severity of chemotherapy-induced oral mucositis. The second reported that polaprezinc reduced oral mucositis in pediatric patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The third trial demonstrated efficacy for a zinc lozenge for postoperative sore throat induced by an endotracheal intubation. SUMMARY: Zinc deficits, dietary or induced by cancer, are common in patients with cancer. Febrile mucositis may better describe the condition linking mucositis with febrile neutropenia. Febrile mucositis disrupts treatment and may be life-threatening. A paradigm shift is needed for a more comprehensive understanding of febrile mucositis. Zinc effects on the thymic immunological network and T lymphocytes during chemoradiotherapy regimens also warrant further investigation.

Intestinal Injury in Heat Stroke.

BACKGROUND: Heat stroke is a life-threatening syndrome that is characterized by its severe clinical symptoms, rapid progression, and high rate of mortality. Recently, research has indicated that a dysfunctional intestinal epithelia barrier plays an important role in the pathophysiology of heat stroke. Protecting the intestines from heat stress had been identified as a potentially effective treatment for patients with heat stroke and may reduce the innate immune response caused by endotoxins in circulation. OBJECTIVES: The aim of this review is to discuss this key event in heat stroke and to describe the mechanism during progression. DISCUSSION: Direct injuries and secondary impairments of the intestine induced by heat stress are discussed; recent studies that refer to intestine-specific prevention and treatment in heat stroke and heat stress-induced injuries are also summarized. CONCLUSIONS: A more detailed pathogenesis of heat stroke needs to be elucidated so that potentially effective means of treatment and prevention of heat stroke can be developed and studied.

The role of the mucosa in modulation of evoked responses in the spinal cord injured rat bladder.

AIMS: Mounting evidence indicates that a variety of factors released from the urothelium or suburothelium can modulate smooth muscle activity. Although the relationship between the mucosa and smooth muscle has been investigated, little is known about the pathophysiologic changes in detrusor-mucosa interactions in neurogenic bladders. The goal of the study was to determine the impact of the mucosa on evoked responses in spinal cord injured (SCI) bladders. METHODS: Urinary bladders were obtained from 6wk SCI rats or age-matched uninjured controls. Ex vivo isometric tension studies were performed and muscarinic receptor expression was measured in bladder tissue with and without mucosa. RESULTS: The magnitude and area of nerve evoked responses in SCI tissue with mucosa was higher than without mucosa. The duration and decay time of nerve-evoked responses were longer in SCI than control tissue irrespective of the mucosa. The level of the muscarinic M2 receptor was decreased in the mucosa of SCI bladders. CONCLUSIONS: Detrusor-mucosa interactions are substantially altered in the neurogenic bladder. After spinal cord injury, an excitatory modulation of smooth muscle contraction by the mucosa emerges, and could be targeted via intravesical treatment in the context of neurogenic bladder dysfunction.

Mucosal Impedance: a New Approach to Diagnosing Gastroesophageal Reflux Disease and Eosinophilic Esophagitis.

PURPOSE OF REVIEW: In this review, we discuss current diagnostic testing modalities for both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) and then introduce mucosal impedance (MI), a novel technology that measures epithelial integrity in real time during endoscopy. We describe the advantages and disadvantages of MI as compared with traditional diagnostic testing. RECENT FINDINGS: We review studies that demonstrate that GERD and EoE have distinct MI patterns, and that physicians can accurately diagnose and distinguish the two during endoscopy with minimal time added to the procedure. We also review studies showing that MI has the capability to assess treatment response in both GERD and EoE and that it can be used to diagnose GERD in patients with extraesophageal reflux symptoms. Mucosal impedance testing is a major advancement in the diagnosis of GERD and EoE. Future studies are planned to assess whether MI can be used as a treatment endpoint in EoE and whether it can be used to predict response to anti-reflux surgery.

Vegetating erosive cutaneous lesions and pyogenic granuloma in the course of mucous membrane pemphigoid: a case report and review of literature.

Mucous membrane pemphigoid (MMP) is a group of chronic autoimmune sub-epithelial blistering disorders, which mostly affect the oral mucosa and the conjunctiva. MMP is very diverse in terms of both the clinical and immunological features (IgG and IgA autoantibodies may react with different antigens). MMP can be induced by infections and medication, including ophthalmologic medication, which may lead to the development of eye lesions. In contrast, a vegetating variant of MMP is extremely rare. Here, we report an MMP case that demonstrated unusual clinical features, that is, pyogenic granulomas on the conjunctivae and extensive vegetating erosions on the skin of intertriginous regions. All these lesions were considered to be induced by unconventional medication containing arsenic.

Current view on the structure and function of the frontal sinus: literature review.

OBJECTIVE: Introduction: Chronic inflammatory diseases of the mucous membranes of the nose, paranasal sinuses, and pharynx are the most common pathology of the upper airways. Pathological processes develop more often in the maxillary and ethmoidal sinuses than in the frontal ones; however, the clinical course of frontitis is more severe. Fundamental understanding of the specific structure of frontal sinuses is crucial in the awareness of the precursors of the onset and development of its pathology, the choice of methods of diagnostics and treatment. The aim: The paper was aimed at the analysis of the publications on current data related to the structure and functions of the human frontal sinus and its structural components. Materials and methods: The bibliosemantic method has been used during the study. Findings of the current research works on the study of the human frontal sinus have been analyzed. RESULTS: Review: The resulting analysis shows that despite the significant amount of research works devoted to the study of the structure and functions of the frontal sinus, the morphofunctional features of its mucosa and the state of local immune protection remained unknown for a long time. CONCLUSION: Conclusions: The resulting literature review showed that the study of the morphofunctional properties of the frontal sinus is relevant to date that is reflected in the number of research works, elucidating its topographoanatomical, histological, physiological and immunohistochemical features.

Structural Reorganization of the Vaginal Mucosa in Stress Urinary Incontinence under Conditions of Er:YAG Laser Treatment.

Structural characteristics of the vaginal mucosa in stress incontinence and its correction by IncontiLase technology were studied. Studies of vaginal biopsy specimens before the exposure showed degenerative and atrophic changes in the stratified squamous epithelium, disorganization of fibrillar structures of the intercellular matrix, and microcirculatory disorders. Studies after Er:YAG laser exposure showed signs of neocollagenogenesis and elastogenesis, foci of neoangiogenesis, reduction of epithelial degeneration and atrophy, and an increase of the fibroblast population. Morphometry showed that the volume density of blood capillaries and the thickness of the epithelial layer increased by 61.1 and 64.5%, respectively. The use of IncontiLase technology in stress incontinence led to structural reorganization of the vaginal mucosa, improving its morphology and function and alleviating the symptoms of incontinence.

Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis.

BACKGROUND & AIMS: Histologic analysis is used to distinguish patients with proton pump inhibitor-responsive eosinophilia (PPI-REE) from those with eosinophilic esophagitis (EoE). It is not clear whether these entities have different etiologies. Exposure to acid reflux can impair the integrity of the esophageal mucosal. We proposed that patients with EoE and PPI-REE might have reflux-induced esophageal mucosal damage that promotes transepithelial flux of allergens. We therefore assessed the integrity of the esophageal mucosal in these patients at baseline and after PPI. METHODS: We performed a prospective study of 16 patients with suspected EoE and 11 controls. Patients had dysphagia, endoscopic signs of EoE, and esophageal eosinophilia (>15 eosinophils/high-power field [eos/hpf]). All subjects underwent endoscopy at baseline; endoscopy was performed again on patients after 8 weeks of treatment with high-dose esomeprazole. After PPI treatment, patients were diagnosed with EoE (>10 eos/hpf; n = 8) or PPI-REE (≤10 eos/hpf; n = 8). We evaluated the structure (intercellular spaces) and function (electrical tissue impedance, transepithelial electrical resistance, transepithelial molecule flux) of the esophageal mucosal barrier. RESULTS: Compared with controls, electrical tissue impedance and transepithelial electrical resistance were reduced in patients with EoE (P < .001 and P < .001, respectively) and PPI-REE (P = .01 and P = .06, respectively), enabling transepithelial small-molecule flux. PPI therapy partially restored these changes in integrity and inflammation in patients with PPI-REE, but not in those with EoE. CONCLUSIONS: The integrity of the esophageal mucosa is impaired in patients with EoE and PPI-REE, allowing transepithelial transport of small molecules. PPI therapy partially restores mucosal integrity in patients with PPI-REE, but not in those with EoE. Acid reflux might contribute to transepithelial allergen flux in patients with PPI-REE. Trialregister.nl number: NTR3480.

Leukocyte-epithelial interactions and mucosal homeostasis.

Many common inflammatory disorders are characterized by the infiltration of neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of critical barrier function that protects from microbes and noxious agents. In such conditions, disease symptoms are complex but directly related to leukocyte effects on the barrier and epithelial cell function. It is now highly regarded that cellular factors such as cytokines and receptor-ligand interactions mediating adhesion of leukocytes to epithelial cells have potent effects on epithelial homeostasis, defined by coordinated proliferation, migration, differentiation, and regulated cell shedding. Certain cytokines, for example, not only alter leukocyte interactions with epithelia through changes in expression of adhesion molecules but also affect barrier function through alterations in the composition and dynamics of intercellular junctions. In particular, inflammation-induced loss of many tight junction molecules, in part, can account for dysregulated cellular proliferation, migration, survival, and barrier function. This review will highlight how neutrophils interact with epithelial cells with particular focus on adhesion molecules involved and signaling events that play roles in regulating mucosal homeostasis and pathobiology. A better understanding of these molecular events may provide new ideas for therapeutics directed at attenuating consequences of pathologic inflammation of mucosal surfaces.

Urothelial mucosal signaling and the overactive bladder-ICI-RS 2013.

There is abundant evidence that the lower urinary tract (LUT) mucosal layer is involved both in mechanosensory functions that regulate bladder contractile activity and in urethral sensation. Changes to the mucosa can be associated with a number of bladder pathologies. For example, alterations of the urothelium and underlying lamina propria at both the molecular and structural levels have been reported in both patients and animals associated with disorders such as bladder pain syndrome and diabetic cystopathy. In contrast to the urinary bladder, much less is known about the urothelium/lamina propria of the bladder neck/proximal urethra. There are important gender differences in the outflow region both anatomically and with respect to innervation, hormonal sensitivity, and location of the external urethral sphincter. There is reasonable evidence to support the view that the mucosal signaling pathway in the proximal urethra is important for normal voiding, but it has also been speculated that the proximal urethra can initiate bladder overactivity. When dysfunctional, the proximal urethra may be an interesting target, for example, botulinum toxin injections aiming at eliminating both urgency and incontinence due to detrusor overactivity.

In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease.

OBJECTIVE: Patients with non-erosive reflux disease (NERD) have impaired oesophageal mucosal integrity (dilated intercellular spaces). Oesophageal mucosal integrity reflects the balance between repeated reflux damage and mucosal recovery. The relationship between mucosal integrity and acid sensitivity is unclear. Oesophageal impedance may be used for in vivo mucosal integrity measurement. We studied acid-induced changes in oesophageal mucosal integrity and acid perception in patients with heartburn. DESIGN: 50 patients with heartburn whithout oesophagitis underwent impedance monitoring before, during and after 10 min oesophageal perfusion with neutral (pH 6.5) and acid solutions (pH 1). Symptoms and impedance were recorded during perfusion. Impedance recovery was assessed for 2 h post-perfusion in ambulatory conditions followed by 24-h impedance-pH study. RESULTS: Reflux monitoring discriminated 20 NERD and 30 functional heartburn (FH) patients. Neutral perfusion caused impedance fall that recovered within 10 min. Acid perfusion caused impedance fall with slow recovery: 6.5 Ω/min (IQR 3.3-12.0 Ω/min). Patients with slow recovery (< 25th percentile) had lower baseline impedance (1273 Ω ± 208 Ω vs. 3220 Ω ± 275 Ω ±, p < 0.01) and more frequent acid sensitivity (10/12 vs. 4/12, p = 0.04) than those with fast (> 75th percentile) recovery. Patients with NERD had lower baseline impedance (1669 ± 182 Ω vs. 2384 ± 211 Ω, p = 0.02) and slower impedance recovery (6.0 ± 0.9 Ω/min vs. 10.7 ± 1.6 Ω/min, p = 0.03) than patients with FH. CONCLUSION: Impaired mucosal integrity might be the consequence of repeated reflux episodes with slow recovery. Mucosal integrity, recovery capacity and symptom perception are linked. Low basal impedance and slow recovery after acid challenge are associated with increased acid sensitivity.

Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro.

BACKGROUND AND AIMS. Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. However, the influence of acid and/or bile acids on human esophageal epithelial barrier function and the tight junction (TJ) proteins has not been fully elucidated. The aim of the study is to investigate the esophageal barrier function and TJ expression in healthy subjects and patients with GERD. The functionality of esophageal mucosa exposed to bile salt deoxycholic acid (DCA) and trypsin has been studied in vitro. MATERIAL AND METHODS. Endoscopic biopsies from healthy controls and patients with GERD-related symptom with endoscopic erosive signs, as well as esophageal mucosa taken from patients undergoing esophagectomy were evaluated in Ussing chambers and by western blot and immunohistochemistry. RESULTS. The esophageal epithelium from GERD patients had lower electrical resistance and higher epithelial currents than controls. Claudin-1 and -4 were significantly decreased in GERD patients. The bile salt DCA in the low concentration of 1.5 mM and trypsin increased the resistance and claudin-1 expression, while the higher concentration of 2.5 mM DCA and trypsin decreased the resistance and the claudin-3, -4 and E-cadherin expressions. CONCLUSION. In addition to acidic reflux, duodenal reflux components, such as bile salts and trypsin, have the potential to disrupt the esophageal barrier function, partly by modulating the TJ proteins. However, the expression of TJ is dependent on both the refluxed material as well as the concentration of the bile salt.

Impact of gastro-oesophageal reflux on microRNA expression, location and function.

BACKGROUND: Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett's oesophagus. Barrett's oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett's oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett's oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis. METHODS: Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A). RESULTS: miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation. CONCLUSIONS: Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These miRNAs localised to the basal layer of the oesophageal epithelium. They reduced proliferation and increased apoptosis, and may play roles in regulating epithelial restoration in response to injury caused by gastro-oesophageal reflux.

Different reactions of human nasal and Eustachian tube mucosa after hyperbaric oxygen exposure: a pilot study.

Impairment of Eustachian tube function has been observed after hyperbaric oxygen treatment as well as after diving on oxygen used as breathing gas. The aim of the present study was to evaluate the influence of hyperbaric oxygen exposure on Eustachian tube ventilatory function and airflow characteristics of the nose. Six police task force divers performing two consecutive dives within a regular training schedule on oxygen were examined. Middle ear impedance, and nasal airflow velocities before and after diving as well as on the morning after the dive day were measured. Middle ear impedance decreased overnight in comparison to pre-dive values (P = 0.027) as well as compared to the value after the first dive (P = 0.032). Rhinoflowmetry did not reveal any changes of nasal airflow velocities related to the dives. Furthermore, no association between middle ear impedance and nasal airflow velocities was found. An impairment of Eustachian tube ventilatory function was obtained after hyperbaric oxygen exposure during dives employing oxygen as breathing gas. This impairment, however, was not associated with altered airflow characteristics of divers' noses. Thus, it seems unlikely that hyperbaric oxygen exerts an effect on the nasal mucosa similar to that on the Eustachian tube mucosa.

[Modern approaches to the treatment of patients with overactive bladder and urge urinary incontinence].

Overactive bladder (OAB) is found in 20% of patients with various disorders of urination, and the imperative urinary incontinence diagnosed in one third of these patients. The study was aimed to improvement the treatment outcomes in OAB women with imperative incontinence and obstructive urination disorders by using a combination of alpha1-adrenoblockers and PDE-5 inhibitors, and to evaluation of relationship between clinical and urodynamic manifestations of the disease. The state of the microcirculation of the bladder mucosa before and after treatment was also evaluated. We have examined and treated 40 women aged 17 to 69 years with disease duration ranged from 1 to 20 years. Patients received combination of al-adrenoblocker alfuzosin (dalfaz) 5 mg at night and reversible selective PDE5 inhibitor tadalafil (Cialis) 5 mg daily in the morning for a month. After treatment, according to the uroflowmetry and cystometry data, the time of urination was reduced, urinary volume and maximum urinary flow rate, as well as cystometric capacity have increased; involuntary detrusor contractions in the bladder filling phase (spontaneous or provoked) became less, or absent. According to the results of ultrasound examination, residual urine volume has decreased. Laser Doppler flowmetry showed an increase of neurogenic tone in precapillary, bypass coefficient and microcirculation effectiveness index, increase in microcirculation index and the coefficient of variation, indicating an improvement of microcirculation in the bladder mucosa. As a result of treatment, the clinical effect was seen in 29 (73%) patients, urinary incontinence was noted only in 6 (15%) patients.