Mucosal Irritation Research Articles

Novel thermosensitive in situ gel based on poloxamer for uterus delivery

Side effects and drug residues are major concerns affecting hormone therapy of bovine reproductive diseases. Fertility-promoting intrauterine infusion liquid (FPL), an effective alternative to hormone therapy, is associated with short retention time and low therapeutic efficacy. To address these problems, we developed a thermosensitive in situ gel based on poloxamer 407 for local uterine administration. To achieve the desired gelling temperature and enhance local retention property, we added poloxamer 188 and HPMC to the formulation containing poloxamer 407 and FPL. After screening was performed, the optimized formulation showed good temperature sensitivity in vitro and in vivo. Gelation temperature was approximately 27°C. In vitro release tests showed that icariin (the major active compound in FPL) was slow released from in situ forming gel. After the gel was locally administered, uterine and ovarian indexes were significantly increased in the gel group compared with the control group (P<0.05). The serum estradiol level of the gel group was significantly higher than that of the control group (P<0.01). Histological evaluation did not show mucosa irritation in the gel group. Therefore, the proposed in situ forming gel system based on poloxamer 407 is a promising local drug delivery system to treat bovine uterine diseases.

Gastric Adenocarcinoma in patients with Roux-en-Y Gastric bypass: A case series

/10.10 15 A mmo ence: . gedr@ The incidence of gastric cancer is approximately 24,000 cases per year with a mortality of 14,000 cases per year. There has been an increasing incidence of proximal gastric cancer and gastroesophageal junction cancer in the United States over the past 5–10 years [1]. Gastric cancer in patients who had previously undergone gastric restrictive surgery and gastric bypass has been reported but is rare. Seventeen case reports and series have been performed describing patients with gastric cancer after undergoing gastric bypass surgery [2]. In the majority of patients who had undergone previous Roux-en-Y gastric bypass surgery, gastric cancer developed in the excluded stomach, leading to delayed diagnosis. Unfortunately, management for these patients is difficult, given their often late diagnoses, which results in the advanced nature of their cancers when symptoms eventually develop [2]. Two cases of gastric adenocarcinoma in patients after Roux-en-Y gastric bypass will be described.

Onbeş yaşındaki çocukta doksisikline bağlı gelişen özofagus ülseri

If tetracycline derivatives are not taken with sufficient water, the drugs can cause esophageal mucosal irritation. We report a 15-year-old child, in whom doxycycline caused direct damage to the mucosa of the esophagus, resulting in esophagitis and peptic ulcer. Drug-induced esophagitis can develop in hours or days with typical clinical symptoms of heartburn, dysphagia and odynophagia. The patient's history of drug intake is important, and upper gastrointestinal system endoscopy is used for the diagnosis. In this article, we present a 15-year-old patient with esophageal ulcer developing after doxycycline treatment

Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven asthma

Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven asthma

Extraction analysis of dental materials for safety evaluation using human oral mucosa model

Various methods of the extraction test is currently available for the biological safety evaluation of dental materials. Hence, setting of the appropriate extraction conditions such as extraction media appropriate to the materials, extraction temperature, and extraction time would be required. In this study, analysis of the dental materials that is used while in contact with oral mucosa was carried out in term of their selections, sample preparations, extraction, in order to provide the foundation for the biological safety evaluation of medical devices that is alternative to the animal studies. Dental materials of restorative composite resin, chemical cured denture base resin, and polyvinyl siloxane impression materials were selected and the SPU-ZDEC (Zinc diethyldithiocarbamate) was used as the positive control. They were all extracted according to the ISO 10993-12. Visual inspection, pH meter, Ultimate 3000 UHPLC, UltraflexⅢ TOF/TOF, and UPLC were used as the method of extracted solution analysis. As the results, there was no foreign materials nor impurities in all of test samples during visual inspection of the appearance. The pH was near the neutral value of 7, except for the restorative composite resin and the blank test solution. Finally, the detailed analysis of extracted solution showed evidence of main components of materials such as bisphenol A glycerolate dimethacrylate, diurethane dimethacrylate, triethylene glycol dimethacrylate, and zinc diethyldithiocarbamate. The result of this study will provide useful information on safety evaluation of tested materials including the sample preparation method for the alternative test method to animal study such as mucosa irritation test.

Chitosan-isoniazid conjugates: Synthesis, evaluation of tuberculostatic activity, biodegradability and toxicity

Novel water-soluble chitosan-isoniazid conjugates were synthesized by two methods: (1) the carbodiimide method using isoniazid (INH) and N-(2-carboxyethyl)chitosan (CEC), and (2) the reaction between INH and N-(3-chloro-2-hydroxypropyl)chitosan (CHPC). The solubility of the conjugates under physiological conditions was enhanced by phosphorylation. Method (1) is preferable in terms of obtaining conjugates with a high content of active substance; depending on reaction conditions, the degree of substitution in the INH-CEC conjugates varies from 0.08 tо 0.39. Ultrasound treatment increased the reaction rate by a factor of 1.3–1.5, but caused partial degradation of the polymer. Consecutive modification led to a considerable decrease in polymer biodegradability in the following order: chitosan>CEC or CHPC>conjugate. In vitro screening of the antimicrobial activity against Mycobacterium tuberculosis H37Rv demonstrated a comparable or slightly higher minimum inhibitory concentration for conjugates than for INH itself (0.20, 0.25, and 1.05μg INH/mL for INH, CEC-INH, and CHPC-INH, respectively). A slug mucosal irritation test employing Limax flavus revealed a lower toxicity for the conjugates than for INH by a factor of 3–4; the most noticeable toxicity decrease was observed for the conjugates obtained by method (1). Studies of acute toxicity in mice revealed a 3–4-fold increase in median lethal dose for the conjugates compared with INH (LD50 210, 850, and 650mg INH/kg for INH, CEC-INH, and CHPC-INH, respectively).

Management of pain and sublingual hematoma caused by suture irritation after implant surgery: A clinical report

Hematoma in the sublingual region is an adverse consequence of implant surgery in the mandibular posterior region. Improved knowledge and understanding of the anatomy as well as the use of advanced radiographic imaging have all contributed to minimizing adverse surgical complications in this region. Delayed sublingual hematoma caused by suture irritation after implant surgery has not previously been reported. This article describes the management of a patient with a delayed sublingual hematoma after implant surgery in the posterior mandible had been performed. No evidence of encroachment of the vascular structures was noted at the time of implant surgery. However, at a 48-hour follow-up, the patient presented with severe pain and irritation of the sublingual mucosa, along with extravasation and a collection of blood in the sublingual region. Based on the patient’s symptoms and clinical signs, the source of the problem was determined to be the stiff tags of polypropylene suture, which had been used to attain primary closure of the surgical flaps. The situation was conservatively and successfully managed by the use of a custom soft tissue guard to protect the patient’s sublingual mucosa and the tongue from the stiff suture tags. Various suture materials and measures for preventing and managing similar situations are discussed in this article.

Encapsulation of alendronate sodium by nanoprecipitation and double emulsion: From preparation to in vitro studies

Alendronate sodium is an active molecule indicated as first line regimen for osteoporosis treatment. Use of this drug presents, however, some shortcomings such as low oral bioavailability and gastrointestinal mucosa irritation. Nanotechnology remains an attractive approach to overcome such limitations of conventional pharmaceutical forms. However, encapsulation of hydrophilic molecules like alendronate represents a real challenge. Preparation, characterization and drug release behavior of polycaprolactone based nanoparticles loaded with alendronate sodium were investigated in this work. Two strategies were used to prepare these nanocarriers: double emulsion evaporation and nanoprecipitation. Operating conditions were monitored to produce biocompatible nanoparticles with good properties. Both techniques gave nanoparticles with mean diameter in the range of 200–450nm. Encapsulation efficiency of selected formulae reached 34% for double emulsion and 18% for nanoprecipitation, respectively. Highest drug loading was 20.7% for double emulsion and 8.2% for nanoprecipitation, respectively. For both methods, an increase of polymer molecular weight and polymer amount led to an increase of particle size. For nanoprecipitation, oil to water phase exerted also a significant effect on particle size. The increase of stabilizer amount or the use of rotoevaporation rather than continuous stirring at ambient temperature decreased particles size. Prepared nanoparticles exhibited sustained release of alendronate. When the same polymer amount and molecular weight was used, drug release of the selected formulae was faster for nanoparticles formulated by the nanoprecipitation method. However, release profiles were similar for both techniques with a first rapid release phase followed by a more prolonged phase. Analysis of in vitro release data showed also that active release mechanism relied on a combination of drug diffusion and polymer relaxation phenomena.

2077859 Ultrasound In HCC Surveillance: What Is The Quality Of Ultrasound And What Factors Affect Quality?

2077859 Ultrasound In HCC Surveillance: What Is The Quality Of Ultrasound And What Factors Affect Quality?

Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats

Context: Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function.Objective: We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats.Materials and methods: Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction.Results: Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure.Discussion and conclusion: Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.)

Prevalence of and risk factors for symptomatic dry eye disease in Singapore

BackgroundThe aim of this study was to describe the prevalence and risk factors of symptomatic dry eye disease (SDED) in Singapore.MethodsA cross‐sectional dry eye survey was carried out using the McMonnies dry eye questionnaire. Members of the public were interviewed at the 46 (out of 62) randomly‐selected mass rapid transit (MRT) stations and their vicinity. A total of 1,004 questionnaires were collected from participants aged between 15 and 83 years. Symptomatic dry eye disease (SDED) was defined as at least one of five self‐reported symptoms that were reported as often or constantly. Non‐dry eye (NDE) subjects were those with no related symptoms reported. Prevalence of symptomatic dry eye disease in the studied population and confidence interval (CI) were calculated. Risk factors were also evaluated using logistic regression analysis at 95% CI.ResultsThe prevalence for symptomatic dry eye disease was found to be 12.3 per cent with prevalence greater in females than males. Symptomatic dry eye disease was significantly associated with contact lens wear (odds ratio [OR] 2.96, 95% CI: 1.81 to 4.83), those having had previous treatment for dry eye (OR 2.09, 95% CI: 1.33 to 3.29), those taking medication (OR 1.84, 95% CI: 0.99 to 3.44), those with unusual sensitivity of eyes (OR 3.04, 95% CI: 1.92 to 4.83), constant mucous membrane dryness (OR 4.11, 95% CI: 1.62 to 10.45) and irritation on waking (OR 2.38, 95% CI: 1.34 to 4.22). Smoking was not found to be associated with symptomatic dry eye disease.ConclusionSingapore has a symptomatic dry eye disease prevalence of 12.3 per cent and was associated with contact lens wear, those who had previous treatment for dry eye, medication, those having unusual sensitivity of eyes, mucous membrane dryness and waking irritation. These new data will be of value to the eye‐care community in Singapore and elsewhere.

Glyphosate: Surfactant herbicide poisoning - Is it mild?

Glyphosate Surfactant is a nonselective widely used herbicide in agriculture, forestry, industrial weed control, lawn, garden and aquatic environments. They have favorable toxicity with occupational and accidental exposures. The toxicity in humans is mucosal and gastrointestinal irritation, hypotension, metabolic acidosis, pulmonary insufficiency, and oliguria. Patient may appear asymptomatic for many hours before slowly lapse into a hypotensive, apparently nonhypovolaemic shock that can often ends fatally. We hereby report a case of a 25-year-old male patient who was admitted to our tertiary care hospital following suicidal consumption of around 250-300 ml of herbicide containing glyphosate (glypho ; ). Initially, gastric lavage done and the patient was managed with intubation and mechanical ventilation. He also developed acute renal failure, and renal function reverted to normal after four sittings of hemodialysis. Patient was successfully treated and discharged home. This case report emphasizes on timely systemic supportive measure as the sole method of treatment since this poison has no specific antidote.

Evaluation of Oral Mucosa Irritation produced by Ozone Gel

Evaluation of Oral Mucosa Irritation produced by Ozone Gel

Oral delivery of capsaicin using MPEG-PCL nanoparticles

To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality. CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining. CAP/NPs had an average diameter of 82.54 ± 0.51 nm, high drug-loading capacity of 14.0% ± 0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation. CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.

Prevalence of and relationship between rhinoconjunctivitis and lower airway diseases in compost workers with current or former exposure to organic dust

The relationship between allergic rhinitis and allergic asthma is well characterized. However, it remains unknown whether an association exists between symptoms of upper and lower airway diseases and occupational bioaerosol exposure beyond the scope of allergy. The current cross-sectional study focuses on 190 current and 59 former compost workers exposed to bioaerosols. Work-related symptoms indicative of conjunctivitis, rhinitis and lower airway irritation were assessed and compared with 38 non-exposed control subjects. Allergic asthma was diagnosed using a calculated score, and chronic obstructive pulmonary disease (COPD) was spirometrically determined. 12 current, 8 former and 5 non-exposed subjects were diagnosed with allergic asthma and excluded from further analysis. Multivariate logistic regression models suggested that cough and chronic bronchitis in current compost workers were associated with eye irritation (OR 2.75 (0.93-8.07); OR 7.22 (1.12-46.5)). Chronic bronchitis in former workers was strongly associated with work-related eye irritation (OR 38.6 (1.33->1000) and nose irritation (OR 25.0 (1.21-513)). After excluding allergic asthmatics, there was no evidence that eye or nose irritation was due to an underlying atopic disease, but rather to non-allergic mucous membrane irritation syndrome. Therefore, the higher incidence of chronic bronchitis in former compost workers may reflect a chronic irritative process triggered by exposure to bioaerosols.

Assessment of sick building syndrome and its associating factors among nurses in the educational hospitals of Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background:Sick Building Syndrome is a diseases associated with indoor air quality accompanied with symptoms such as headache, dizziness, nausea, coughing and sneezing, irritation of eyes, throat and nose mucous membrane, and skin itching and inflammation. The purpose of this study was to investigate the symptoms of the syndrome and its related factors among nurses in teaching hospitals of Shahid Sadoughi University of Medical Sciences, Yazd, Iran.Methods:The study was conducted amongst nurses of three teaching hospitals of Shahid Sadoughi University of Medical Sciences, in Yazd. In this study the MM040EA questionnaire of sick building syndrome and indoor air quality was used and data extracted from the questionnaires were analyzed using the chi-square test and t-test.Results:The prevalence of sick building syndrome was 86.4%. The prevalence of the syndrome was in no association with age, gender, employment history and type of shift work. The most common symptoms reported by nurses included headache, fatigue and dry hands. Lack of sense of airflow, unpleasant odor in workplace (P<0.05), and also the amount of workload (P<0.001) were in relation with sick building syndrome.Conclusion:The high prevalence of sick building syndrome symptoms in the nursing environment was associated with factors of unpleasant odor and high workload of environment. So improvement of environmental conditions such as increasing the efficiency of the HVAC system, increasing fresh air flow in the sector, reducing the nurses workload as well as enhancing the quality of working life, will motivate the nurses and increase productivity in the workplace.

Selecting solvent and solubilizer for puerarin nasal drops by solubility and irritation

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient, the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30% PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.

PO-0413 Trigeminal Odours Released By Healthcare Products Activate Olfactory And Pain Cortical Areas In Preterm And Full Term Newborns

Background/aim Hospitalised newborns are highly exposed to nosocomial odorous substances (OS) triggering possibly the intranasal trigeminal subsystem. Irritation of the nasal mucosa can induce pain and activations in pain processing areas in adults We aimed to evaluate cortical activation in trigeminal/olfactory and pain areas following OS exposure in newborns. Methods Forty-four newborns (17 full-terms, 12 preterms at term PMA and 15 preterms – water (control); – a hand rub (DES60 ® ) diluted to match the odour’s intensity released by hands; – an adhesive remover (Convacare ® ). We recorded bilaterally cortical activation in orbito-frontal gyri (OFG), prefrontal (PFC) and somatosensory (S1 and S2) cortices during 40s (10s-baseline, 10s-presentation, 20s-post-stimuli) by multichannel-NIRS. HbO2 changes were analysed from baseline (ANOVA) and by subgroups (Kruskall-Wallis). Results In the whole population, we observed: – no activations for water. – cortical activations (HbO 2 increase) for DES60 ® (p ® (p We noticed significant profiles of response for all infant’s subgroups, in at least one olfactory and one pain processing areas. The average magnitude of HbO 2 increase from baseline was higher in full-terms vs both subgroups of preterms: 8.5(2.8–12.6) µmol/l vs 5.9(2.6–10.4) and 5.7(1.8–9.2) µmol/l for DES60 ® (p Conclusion Full-term and preterm newborns can perceive OS at a cortical level. Exposure to OS can activate trigeminal/olfactory and pain processing areas and may induce discomfort/pain in newborns.

Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2±1.3nm, -41.5±2.71mv and 81.9±2.43%, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing.

Seasonal Variation in Schools’ Indoor Air Environments and Health Symptoms among Students in an Eastern Mediterranean Climate

ABSTRACTThe indoor air quality (IAQ) in classrooms highly affects the health and productivity of students. This article aims to clarify seasonal variation in indoor environment and sick building syndromes (SBS) symptoms in an Eastern Mediterranean climate. A series of field measurements were conducted during the fall and winter seasons from October 2011 to March 2012 in 12 naturally ventilated schools located in the Gaza Strip. Data on environmental perception and health symptoms were obtained from 724 students by using a validated questionnaire. The results showed that indoor PM10 and PM2.5 concentrations were 426.3 ± 187.6 μg/m3 and 126.6 ± 94.8 μg/m3, respectively. The CO2 concentrations and ventilation rate widely exceeded their reference values during the winter season. The prevalence rates of general symptoms were relatively high at baseline assessment in the fall season and increased significantly during follow-up in the winter season. Significant increases in disease symptoms such as mucosal irritation and pre-existing asthma symptoms among students could be related to poor indoor air quality. Five distinct groups of SBS symptoms from factor analysis of students’ related symptoms were significantly correlated with PM10 and PM2.5, CO2, ventilation rate, and indoor temperature. As vulnerable children, this situation negatively affects their school performance and health.