Determining the effect of ocular chemical injuries on topical drug delivery.

Ocular chemical injuries (OCIs) commonly cause ocular damage and visual loss and treatment uses topical therapies to facilitate healing and limit complications. However, the impact of chemical injury on corneal barrier function and treatment penetration is unknown. Therefore, the aim of this study was to determine the effect of OCI on drug penetration and absorption. Porcine corneal explants were used to assess histological damage, electrical resistance, and the trans-corneal penetration/corneal adsorption of reference compounds (sodium fluorescein and rhodamine B) and dexamethasone. Corneal explants were injured with either 1 M sulfuric acid, or 1 M sodium hydroxide. Dexamethasone penetration was measured using high-performance liquid chromatography (HPLC) and that of fluorescein and rhodamine using fluorescence. Dexamethasone corneal adsorption was measured using enzyme-linked immunoabsorbant assay (ELISA). Both acid and alkaline injuries reduced trans-corneal electrical resistance. NaOH injury increased hydrophilic fluorescein penetration (NaOH 8.59 ± 1.50E-05 cm.min-1 vs. Hanks' Balanced Salt Solution (HBSS) 1.64 ± 1.01E-06 cm.min-1) with little impact on hydrophobic rhodamine B (1 M NaOH 6.55 ± 2.45E-04 cm.min-1 vs. HBSS 4.60 ± 0.972E-04 cm.min-1) and dexamethasone penetration (1 M NaOH 3.00 ± 0.853E-04 cm.min-1 vs. HBSS 2.69 ± 0.439E-04 cm.min-1). By contrast, H2SO4 decreased trans-corneal penetration of hydrophilic fluorescein (H2SO4 1.16 ± 14.2E-07 cm.min-1) and of hydrophobic dexamethasone (H2SO4 1.88 ± 0.646E-04 cm.min-1) and rhodamine B (H2SO4 4.60 ± 1.42E-05 cm.min-1). Acid and alkaline OCI differentially disrupted the corneal epithelial barrier function. Acid injury reduced penetration of hydrophobic dexamethasone and rhodamine B as well as hydrophilic fluorescein, which may translate clinically into reduced drug penetration after OCI, while alkaline injury increased fluorescein penetration, with minimal effect on dexamethasone and rhodamine B penetration.

Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial.

BACKGROUND: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis. DESIGN AND SETTING: A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020. PARTICIPANTS: Patients (n = 105) aged 18-75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included. INTERVENTIONS: Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion of patients achieving Investigator's Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores. RESULTS: At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6-37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4-68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0-12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported. CONCLUSIONS AND RELEVANCE: Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/ . Date first registered: 14 November 2019.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

Extreme Low Cytosolic pH Is a Signal for Cell Survival in Acid Stressed Yeast.

Yeast biomass is recycled in the process of bioethanol production using treatment with dilute sulphuric acid to control the bacterial population. This treatment can lead to loss of cell viability, with consequences on the fermentation yield. Thus, the aim of this study was to define the functional cellular responses to inorganic acid stress. Saccharomyces cerevisiae strains with mutation in several signalling pathways, as well as cells expressing pH-sensitive GFP derivative ratiometric pHluorin, were tested for cell survival and cytosolic pH (pHc) variation during exposure to low external pH (pHex). Mutants in calcium signalling and proton extrusion were transiently sensitive to low pHex, while the CWI slt2Δ mutant lost viability. Rescue of this mutant was observed when cells were exposed to extreme low pHex or glucose starvation and was dependent on the induced reduction of pHc. Therefore, a lowered pHc leads to a complete growth arrest, which protects the cells from lethal stress and keeps cells alive. Cytosolic pH is thus a signal that directs the growth stress-tolerance trade-off in yeast. A regulatory model was proposed to explain this mechanism, indicating the impairment of glucan synthesis as the primary cause of low pHex sensitivity.

Is it time for a change in the approach to chemical burns? The role of Diphoterine® in the management of cutaneous and ocular chemical injuries.

A multitude of household and occupational compounds have the potential to induce chemical burns to the eye and skin. Without prompt intervention, irreversible visual loss and disfigurement may prevail. Diphoterine® and Hexafluorine® are amphoteric and hypertonic chelating solutions used in the management of general chemical and hydrofluoric acid burns, respectively. They rapidly neutralise both acid and alkali agents without heat release and limit diffusion, making them superior to water irrigation alone. However, although Diphoterine® and Hexafluorine® uptake is slowly increasing in industrial workplaces, there is a paucity of education and use in both emergency departments and plastic surgery units worldwide. Herein, we present a case report of combined ocular and cutaneous acid burn treated with Diphoterine®, together with a review of the current supporting literature.

Ten-year epidemiology of chemical burns in western Zhejiang Province, China.

BACKGROUND: Chemical burns occur frequently in western Zhejiang Province. This study documents the epidemiology of chemical burns in the region using burn data from a local specialized hospital. Results from this analysis will assist in the planning of prevention strategies for high-risk occupations and groups. METHODS: A 10-year retrospective analysis was conducted for all patients with chemical burns admitted to the Department of Burn and Plastic Surgery from January 2004 to December 2013. Information obtained for each patient included demographics (gender, age, occupation and education), location of the burn, cause of the burn, and categories of chemicals. Data regarding the season of admittance, prehospital treatment, wound site/size (area, region, and depth), accompanying injuries, operations, length of hospital stay and mortality were also assessed. RESULTS: A total of 690 patients (619 males, 71 females; average age: 30.6±12.4 years) were admitted to the department for chemical burns. Over the 10-year period, the incidence of chemical burns showed an increasing tendency. Chemical burns occurred most frequently in patients aged 20-59 years (94.79%). Most of the chemical burns were work-related, primarily in private enterprises (47.97%) and state-owned enterprises (24.93%). Operations (68.99%) and machine problems (17.26%) were the main causes of chemical burns in the workplace. With regard to burns caused by chemicals, most were caused by acids (72.01%), with hydrofluoric acid and sulphuric acid causing 51.45%. Most chemical burns occurred in the summer and autumn seasons (61.02%). The burn size was <10% of the total body surface area (TBSA) for 445 patients (64.49%), while only 26 patients (3.76%) had burns covering >40% TBSA. The most common burn sites were the upper extremities (31.57%), lower extremities (19.86%), and head and neck (28.83%). Most patients (581 (84.20%)) received water washing treatment on site immediately after exposure. The most common accompanying injuries included inhalation injury, ocular burns and digestive tract injury. The average hospital stay was 17.0±23.1 days (range 1-333 days). Surgery was performed in 146 patients (21.16%), and the overall mortality rate was 0.58%. CONCLUSIONS: Chemical burns are preventable. The high morbidity of chemical burns in western Zhejiang Province is related to the industrial structure of the area. Governmental management in the fields of production, transportation, and utilization of chemicals could be improved. Workplaces have the responsibility to provide safe work environments and equipment, as well as occupational education and safety training for high-risk work groups.

Top five chemicals resulting in injuries from acute chemical incidents­Hazardous Substances Emergency Events Surveillance, nine states, 1999-2008.

PROBLEM/CONDITION: The Toxic Substances Control Act Chemical Substance Inventory lists >84,000 chemicals used in commerce (http://www.epa.gov/oppt/existingchemicals/pubs/tscainventory/basic.html). With chemicals having a multitude of uses, persons are potentially at risk daily for exposure to chemicals as a result of an acute chemical incident (lasting <72 hours). Depending on the level of exposure and the type of chemical, exposure can result in morbidity and, in some cases, mortality. REPORTING PERIOD: 1999-2008. DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events Surveillance (HSEES) system was operated by the Agency for Toxic Substances and Disease Registry during January 1991-September 2009 to collect data that would enable researchers to describe the public health consequences of chemical incidents and to develop activities aimed at reducing the harm from such incidents. This report identifies the top five chemicals that caused injuries in the nine states (Colorado, Iowa, Minnesota, New York, North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated in HSEES during its last 10 full years of data collection (1999-2008). RESULTS: Of the 57,975 incidents that were reported, 54,989 (95%) involved the release of only one chemical. The top five chemicals associated with injury were carbon monoxide (2,364), ammonia (1,153), chlorine (763), hydrochloric acid (326), and sulfuric acid (318). Carbon monoxide and ammonia by far caused the most injuries, deaths, and evacuations. Chlorine, while not in the top 10 chemicals released, was in the top five chemicals associated with injury because of its hazardous properties. INTERPRETATION: Multiple measures can be taken to prevent injuries associated with the top five chemicals. Because many carbon monoxide releases occur in residential settings, use of carbon monoxide detectors can prevent injuries. Substituting chemicals with less lethal alternatives can result in mitigating injuries associated with ammonia. Routine maintenance of equipment and engineering controls can reduce injuries associated with chlorine and sulfuric acid, and proper chemical handling training can reduce injuries associated with hydrochloric acid. PUBLIC HEALTH IMPLICATIONS: Understanding the most frequently reported locations where carbon monoxide, ammonia, chlorine, hydrochloric acid, and sulfuric acid are released along with the most frequently reported contributing factors can help mitigate injuries associated with these releases. Prevention initiatives should focus on educating the public and workers about the dangers of these chemicals and about proper handling of these chemicals along with routine maintenance of equipment.

Do group responses mask the effects of air pollutants on potentially sensitive individuals in controlled human exposure studies?

To establish primary National Ambient Air Quality Standards (NAAQS) for criteria air pollutants such as nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2), US EPA relies in part on controlled human exposure studies. It has been suggested that evaluating average responses for all participants in these studies may not reflect the responses of sensitive participants in these studies. To evaluate this, we identified controlled exposure studies with multiple exposure concentrations or durations that provided individual-level lung function data. Based on individual lung function responses at specific exposure concentrations and the slope of individual concentration-response curves, we identified 12 participants out of a total of 208 participants in 12 studies who were potentially sensitive to O3, SO2, or sulfuric acid (H2SO4). We did not identify any participants sensitive to NO2. All of these participants were found to be potentially sensitive only at concentrations that were well above the NAAQS (SO2), above likely ambient concentrations (H2SO4), or at concentrations at which the study reported significant lung function effects for all participants (O3). Based on our analysis, average responses for all participants combined adequately reflect lung function responses for potentially sensitive study participants at concentrations in the range of the current NAAQS.

[Residential cohort approach in industrial contaminated sites: the ERAS Lazio project]. / Lo studio di coorte di popolazione in aree a forte pressione ambientale: il programma ERAS Lazio.

The population-based cohort study is the best design for assessing the possible health effects resulting fromliving in contaminated sites. The ERAS (Epidemiology,Waste disposal, Environment and Health) Project was established to study the health of people living in close proximity to urban solid waste treatment (RU) plants in Lazio. It was conducted using an integrated approach, which consisted in studying mortality and hospital discharges of residential cohorts surrounding urban waste treatment plants. The level of exposure of each address was assigned using pollution dispersion models and studying the effects on mortality and hospital discharges. Further studies were conducted on residents of areas adjacent to waste disposal sites (includingMalagrotta in Rome), incinerators andmechanical biological treatment plants. The final version of the ERAS Report is available at www.eraslazio.it. The residential cohort approach and the combination of environmental and health-related information proved invaluable in the assessment of the health impact of solid waste treatment in Lazio.

Nasogastric tube as protection for recurrent oesophageal stricture: a case report.

This report presents the case of an 8.5-year-old boy with Down syndrome after experiencing extensive caustic injury to the oesophagus and stomach resulting from the accidental ingestion of concentrated sulphuric acid. The patient had undergone 32 unsuccessful endoscopic oesophageal stricture dilatations and stenting procedures performed over a period of 15 mo following the accident. Surgical reconstruction of the oesophagus was not possible due to previous gastric and cardiac surgeries for congenital conditions. Before referring the patient for salivary fistula surgery, the patient received a nasogastric tube with perforations located above the upper margin of the oesophageal stenosis for the passage of saliva and fluid. The tube was well tolerated and improved swallowing; however the backflow of gastric contents caused recurrent infections of the respiratory tract. To overcome these problems, we developed a double lumen, varying diameter, perforated tube for protection of the oesophageal closure. This nasogastric tube was found to be safe and decreased the need for hospitalization and further endoscopic procedures. This newly developed tube can thus be considered as a treatment option for patients with recurrent oesophageal stenosis and contraindications for surgical oesophageal reconstruction.

Photosynthetic and antioxidant responses of Liquidambar formosana and Schima superba seedlings to sulfuric-rich and nitric-rich simulated acid rain.

To study whether differential responses occur in photosynthesis and antioxidant system for seedlings of Liquidambar formosana, an acid rain (AR)-sensitive tree species and Schima superba, an AR-tolerant tree species treated with three types of pH 3.0 simulated AR (SiAR) including sulfuric-rich (S-SiAR), nitric-rich (N-SiAR), sulfate and nitrate mixed (SN-SiAR), we investigated the changes of leaf necrosis, chlorophyll content, soluble protein and proline content, photosynthesis and chlorophyll fluorescence characteristics, reactive oxygen species production, membrane lipid peroxidation, small molecular antioxidant content, antioxidant enzyme activities and related protein expressions. Our results showed that SiAR significantly caused leaf necrosis, inhibited photosynthesis, induced superoxide radical and hydrogen peroxide generation, aggravated membrane lipid peroxidation, changed antioxidant enzyme activities, modified related protein expressions such as Cu/Zn superoxide dismutase (SOD), l-ascorbate peroxidase (APX, EC 1. 11. 1. 11), glutathione S transferase (GST, EC 2. 5. 1. 18) and Rubisco large subunit (RuBISCO LSU), altered non-protein thiols (NPT) and glutathione (GSH) content in leaves of L. formosana and S. superba. Taken together, we concluded that the damages caused by SiAR in L. formosana were more severe and suffered from more negative impacts than in S. superba. S-SiAR induced more serious damages for the plants than did SN-SiAR and N-SiAR.

Dental erosion and sulfuric ion exposure levels in individuals working with sulfuric acid in lead storage battery manufacturing plant measured with mouth-rinse index.

To investigate dental erosion in employees working with sulfuric acid at a lead storage battery manufacturing plant and level of personal exposure to sulfuric ions, we measured sulfuric ion concentrations in the mouth rinse of those employees. We also measured exposure levels from air samples obtained from 2 employees from the same plant who did not work with sulfuric acid using a portable air sampler. At the same time, we collected and compared their mouth rinses with those from other employees. More specifically, we measured and compared sulfuric ion, calcium, and magnesium concentrations, along with pH levels from the mouth rinse of these two groups. Positive correlations were found between sulfuric ion and calcium concentrations (r=0.61, p<0.005), calcium and magnesium concentrations (r=0.61, p<0.005), Ca/Mg and calcium concentrations (r=0.64, p<0.005), and sulfuric ion and magnesium concentrations (r=0.55, p<0.005). Negative correlations were found between sulfuric ion concentrations and pH levels (r=-0.31, p<0.01), and magnesium concentrations and pH levels (r=-0.32, p<0.01). This suggests that mouth rinse from employees working with sulfuric acid could function as an indicator of sulfuric ion concentration in the work environment. Furthermore, this could lead to the development of a more accurate indicator of individual exposure.

Dental erosion in workers exposed to sulfuric acid in lead storage battery manufacturing facility.

Dental erosion, and specifically its symptoms, has long been studied in Japan as an occupational dental disease. However, in recent years, few studies have investigated the development of this disease or labor hygiene management aimed at its prevention. As a result, interest in dental erosion is comparatively low, even among dental professionals. Our investigation at a lead storage battery factory in 1991 found that the work environmental sulfuric acid density was above the tolerable range (1.0mg/m(3)) and that longterm workers had dental erosion. Therefore, workers handling sulfuric acid were given an oral examination and rates of dental erosion by tooth type, rates of erosion by number of working years and rates of erosion by sulfuric acid density in the work environment investigated. Where dental erosion was diagnosed, degree of erosion was identified according to a diagnostic criterion. No development of dental erosion was detected in the maxillary teeth, and erosion was concentrated in the anterior mandibular teeth. Its prevalence was as high as 20%. Rates of dental erosion rose precipitously after 10 working years. The percentages of workers with dental erosion were 42.9% for 10-14 years, 57.1% for 15-19 years and 66.7% for over 20 years with 22.5% for total number of workers. The percentages of workers with dental erosion rose in proportion to work environmental sulfuric acid density: 17.9% at 0.5-1.0, 25.0% at 1.0-4.0 and 50.0% at 4.0-8.0mg/m(3). This suggests that it is necessary to evaluate not only years of exposure to sulfuric acid but also sulfuric acid density in the air in factory workers.

Traumatic chemical oral ulceration: a case report and review of the literature.

A 34-year-old man experienced extensive oral ulceration as a consequence of attempted ingestion of sulphuric acid as part of an act of deliberate self harm. All oral lesions healed within 28 days after local and systemic therapy. Oral ulceration has many potential causes ranging from physical trauma to malignancy. Chemicals are a less common cause of traumatic ulceration. Most chemical burns are characterised by mild to moderate tissue damage that heals spontaneously within seven to 15 days without scarring.