Smoke Inhalation Research Articles

Cigarette smoke-induced changes in the murine vocal folds: a Raman spectroscopic observation.

Raman spectroscopic methods are being projected as novel tools to study the early invisible molecular level changes in a label-free manner. In the present study, we have used Raman spectroscopy to explore the earliest biochemical changes in murine vocal folds in response to time-bound cigarette smoke exposure. Mice were exposed to cigarette smoke for 2 or 4-weeks through a customized smoke inhalation system. The larynx was collected and initial evaluations using standard methods of analysis such as histopathology and immunofluorescence was performed. Concurrent unstained sections were used for Raman imaging. Two common pathological features of vocal fold disorders including alterations in collagen content and epithelial hypercellularity, or hyperplasia, were observed. The mean spectra, principal component analysis, and Raman mapping also revealed differences in the collagen content and hypercellularity in the smoke exposed tissues. The differences in 2-week exposed tissues were found to be more prominent as compared to 4-week. This was attributed to adaptive responses and the already reported biphasic effects, which suggest that collagen synthesis is significantly reduced at higher cigarette smoke concentrations. Overall findings of the study are supportive of the prospective application of Raman imaging in monitoring changes due to cigarette smoke in the vocal folds.

Nebulized heparin for inhalation injury in burn patients: a systematic review and meta-analysis.

BackgroundSmoke inhalation injury increases overall burn mortality. Locally applied heparin attenuates lung injury in burn animal models of smoke inhalation. It is uncertain whether local treatment of heparin is benefit for burn patients with inhalation trauma. We systematically reviewed published clinical trial data to evaluate the effectiveness of nebulized heparin in treating burn patients with inhalation injury.MethodsA systematic search was undertaken in PubMed, the Cochrane Library, Embase, Web of Science, the Chinese Journals Full-text Database, the China Biomedical Literature Database and the Wanfang Database to obtain clinical controlled trails evaluating nebulized heparin in the treatment of burn patients with inhalation injury. Patient and clinical characteristics, interventions and physiological and clinical outcomes were recorded. Cochrane Risk of Bias Evaluation Tool and the Newcastle–Ottawa Scale were used to evaluate data quality. Potential publication bias was assessed by Egger’s test. A sensitivity analysis was conducted to assess the stability of the results. The meta-analysis was conducted in R 3.5.1 software.ResultsNine trials were eligible for the systematic review and meta-analysis. Nebulized heparin can reduce lung injury and improve lung function in burn patients with inhalation injury without abnormal coagulation or bleeding, but the findings are still controversial. Mortality in the heparin-treated group was lower than that of the traditional treatment group (relative risk (RR) 0.75). The duration of mechanical ventilation (DOMV) was shorter in the heparin-treated group compared to the traditional treatment group (standardized mean difference (SMD) −0.78). Length of hospital stay was significantly shorter than that in the traditional treatment group (SMD −0.42), but incidence rates of pneumonia and unplanned reintubation were not significantly different in the study groups (RRs 0.97 and 0.88, respectively). No statistically significant publication biases were detected for the above clinical endpoints (p > 0.05).ConclusionsBased on conventional aerosol therapy, heparin nebulization can further reduce lung injury, improve lung function, shorten DOMV and length of hospital stay, and reduce mortality, although it does not reduce the incidence of pneumonia and/or the unplanned reintubation rate.

Evidence of health complications caused by mosquito coil smoke inhalation in mouse model

Evidence of health complications caused by mosquito coil smoke inhalation in mouse model

Impact of cigarette smoke and aerobic physical training on histological and molecular markers of prostate health in rats.

Recent evidence suggests that aerobic physical training may attenuate the deleterious effects of cancer risk factors, including smoking. We investigated the effects of cigarette smoke inhalation and aerobic physical training on the expression of steroid receptors and inflammatory and apoptotic proteins in the prostate. Forty male Wistar rats were distributed in four groups: control (CO), exercise (EXE), cigarette smoke exposure (CS), and cigarette smoke exposure with exercise (CS+EXE). For eight weeks, animals were repeatedly exposed to cigarette smoke for 30 min or performed aerobic physical training either with or without the cigarette smoke inhalation protocol. Following these experiments, we analyzed prostate epithelial morphology and prostatic expression of androgen (AR) and glucocorticoid receptors (GR), insulin-like growth factor (IGF-1), B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) via immunohistochemistry. Cigarette smoke exposure stimulated the expression of AR, IGF-1, BCL-2, and NF-κB while downregulating BAX, IL-6, and TNF-α labeling in the prostate. In contrast, aerobic physical training attenuated cigarette smoke-induced changes in AR, GR, IGF-1, BCL-2, IL-6, TNF-α, and NF-κB. This suggests that cigarette smoke stimulates inflammation and reduces apoptosis, culminating in increased prostatic epithelial and extracellular matrices, whereas physical training promoted beneficial effects towards maintaining normal prostate morphology and protein levels.

The Construction of A Sheep Acute Respiratory Distress Syndrome Model Induced by Smoke Inhalation Injury

Objective To establish a model of acute respiratory distress syndrome induced by sheep smoke inhalation lung injury. Methods Nine healthy, 12-24 month old, non-pregnant female sheep were randomly selected, the sheep were divided into three groups, through the internal control of smoke generator device components (CO, CO2, O2, particle concentration and smoke temperature, etc.) to adjust the exposure time of the sheep model construction of smoke. The chest CT were examined before and after exposure to smoke at 6h, 12h, 24h and 48h, respectively. From the smoke exposure 12h endotracheal intubation and mechanical ventilation, by adjusting the ventilator parameters of hypoxemia and hypercapnia, statistical analysis of PaO2/FiO2, PEEP and other indicators, according to the ARDS definition of diagnosis in Berlin definition. Results The CT showed mild inflammation of the lungs in first group, oxygen index of 95% confidence interval [331.13, 353.53]; In second groups, oxygenation index 95% confidence interval [220.09, 383.90]; CT showed airway edema, pulmonary inflammatory exudation and lung injury in third group. Oxygenation index 95% confidence interval of [195.16, 244.84], PEEP>5cm. There was significant difference between the two groups (P<0.05). Conclusions The severity of lung injury can be changed by adjusting the exposure time of smoke inhalation; when the smoke exposure time up to 45 minutes, a stable model of smoke inhalation lung injury in sheep ARDS can be successfully established.

Supportive Care In A Patient With Acute Myeloid Leukemia Through An Integrated Approach Including Yagya Therapy

Background: Acute myeloid leukemia (AML) is a malignant disease of the hematopoietic system that involves infiltration of blood, bone marrow, and other tissues by poorly differentiated hematopoietic cells. Although several treatment methodologies have been employed for the treatment of AML, complete remission and long-term management of this disease is still not achieved. Purpose: As per the classical texts of Ayurveda, the disease that resembles the symptoms associated with malignancy is called Arbuda, and when Rakta (Blood) Dhatu is primarily involved in its manifestation, it is called Raktarbuda, which has associated symptoms of bleeding tendency, anemia, etc. Arbuda may be produced by the vitiation of the three Doshas (i.e. Vata, Pitta and Kapha), and Rakta (blood), Mamsa (muscles) and Medas (fat) Dhatus; hence, treatments, including herbal medicines, that balance these are recommended for the management of the symptoms associated with Arbuda. Yagya Therapy provides pulmonary inhalation of medicinal smoke of multiple herbs (generated through oblation in fire along with chanting of Vedic hymns), which provide therapeutic benefits. The Vedic hymns also contribute to the positive restructuring of the psyche of the patient. Methods: A case report about a female patient, who was suffering from symptoms associated with AML, as well as other associated ailments, has been presented in this article. The patient was prescribed an integrated approach including Yagya Therapy (using an appropriate herbal formulation - hawan samagri), and some other Ayurvedic treatments like decoction of medicinal herbs, Ayurvedic medicines, dietary recommendations, etc. Results: Before starting the integrated approach including the Yagya Therapy (prescribed in the present study), the patient had several complaints including bleeding piles, constipation, vomiting, breathlessness, body pain, head-ache, sleeplessness, loss of appetite, weakness, stress, depression; after taking the integrated approach including Yagya Therapy, the complaints of bleeding piles, vomiting, breathlessness were completely resolved; there was about 75% relief in the complaints of constipation, loss of appetite, body pain; and there was notable relief (about 50%) in the remaining complaints as well. Overal, there was definite improvement in the contition of the patient. Conclusion: The integrated approach including Yagya Therapy showed encouraging results with regards to the management of symptoms associated with AML, as well as other associated ailments.

An Integrated Traditional Therapy Approach Involving Yagya Therapy In Patient With Symptoms Similar to Crohn's Disease

Background: Crohn’s disease (an inflammatory bowel disease - IBD) is a chronic gastrointestinal inflammatory disorder. Common symptoms include rectal bleeding, persistent diarrhea, abdominal pain, extreme fatigue, weight loss, constipation, etc. Although it is a widespread disease, its etiology and mechanism are still not properly understood. Hence, even though several treatment methodologies have been employed for the management of the symptoms associated with the Crohn's disease - side-effect free, long-term management of this disease is still not achieved. Purpose: As per the classical texts of Ayurveda, Pachak Pitta, Saman Vayu and Kledak Kapha are responsible for proper digestion; vikriti (vitiation) of these Doshas can lead to various types of diseases of the gastrointestinal tract. Hence, herbal medicines that balance these Doshas, as well as provide nourishment to the body tissues, can be recommended for the management of the observed symptoms of the disease in the present study. Yagya Therapy provides pulmonary inhalation of medicinal smoke of multiple herbs (generated through oblation in fire along with chanting of Vedic hymns), which provide therapeutic benefits. The Vedic hymns also contribute to the positive restructuring of the psyche of the patient. Methodology: A case report about a male patient, who was suffering from symptoms similar to those found in Crohn's disease, has been presented in this article. The patient was prescribed an integrated approach pivoting on Yagya Therapy (using an appropriate herbal formulation - hawan-samagri), and some other Ayurvedic treatments like decoction of medicinal herbs, dietary restrictions, etc. Results: Before starting the integrated approach involving Yagya Therapy , the patient used to have severe pain in the abdomen, had swelling and stiffness in legs, had constipation, as well as weight loss; after taking the integrated approach involving Yagya Therapy , there was significant relief in the pain, the swelling in the legs was completely resolved, the stiffness in the legs had reduced, constipation was significantly reduced, as well as there was slight increase in weight. Earlier, because of weakness, the patient had difficulty in walking, changing posture from sitting to standing and vice versa, changing side while lying down; after taking the integrated approach, the patient feels an enhanced strength in his legs, has started walking on his own, can change posture from sitting to standing and vice versa on his own, can change side while lying down on his own. Overall, there was definite improvement in the condition of the patient. Conclusion: The integrated approach involving Yagya Therapy showed encouraging results with respect to the management of symptoms similar to those found in Crohn's disease.

Management of the Symptoms associated with Osteoarthritis of the Knee through an Integrated Approach including Yagya Therapy

Background: Osteoarthritis (OA) of the knee is a major cause of mobility impairment. Therapeutic interventions conventionally employed for OA include the use of physiotherapy, patient education and weight control, drug therapy that includes non-opioid analgesics, topical analgesics, opioid analgesics and intra articular steroid injection. At times, cases of OA also extend on to knee arthroplasty (knee- replacement) surgery too. However, side-effect free, long-term management of this disease still remains a challenge. Purpose: Classical Ayurveda locks in the symptoms of Osteoarthritis as Janu Sandhigata Vata, where Janu refers to knee, sandhi is joint and Vata is the air element permeating the knee joint – in this case,.With advancing age, the influence of Vata Dosha increases, resulting in the gradual degeneration of the body. Sandhigata Vata can be defined as a disease of sandhi (articulation) with symptoms of - sandhi shool(shola- pain) (joint pain), sandhi shotha (shotha - inflammation) (inflamation in joints), etc. Hence, the medicinal herbs that balance the Vata Dosha, as well as provide nourishment to the body tissues, are used in the Ayurvedic treatment of OA of the knee. A number of medicinal herbs have been found to be effective in this regard. Yagya Therapy provides pulmonary inhalation of medicinal smoke of multiple herbs (generated through oblation in fire along with chanting of Vedic hymns), which have the potential for the treatment of OA of the knee, and associated difficulties. Methodology: A case report about a male patient, who was suffering from Osteoarthritis (OA) in the right knee, as well as other associated difficulties, has been presented in this article. The patient was prescribed an integrated approach pivoting onYagya Therapy (using an appropriate herbal formulation - hawan-samagri), and some other Ayurvedic treatments like decoction (kwath) of medicinal herbs, Ayurvedic medicines, dietary restrictions, etc. Discussion: Before taking up the integrated approach pivoting on Yagya Therapy (prescribed in the present study), the patient suffered from excruciating knee-pain that resulted in a limping gait. Post-initiation of the prescribed treatment the pain issue accompanied by limping gait is seen to be almost completely resolved. The patient is able to manage long walks up to half a kilometer without experiencing discomfort. . Earlier, the patient had to take support while changing posture from sitting to standing, and vice-versa; now he can change posture without support; Prior to therapy, patient was not able to sit cross legged on floor, which is an integral part of Indian lifestyle – now he does so, sans any discomfort. There is a definite amelioration in the patient’s pain management regime. Conclusion: The present study shows encouraging result with regards to the effectiveness of integrated approach including Yagya Therapy in the treatment of symptoms associated with OA of the knee, and associated complexities.

Atherosclerotic and Hypertensive Cardiovascular Disease are Associated with Death at Sublethal Carboxyhemoglobin Levels: A Postmortem Study.

Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty-five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age-adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age-adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age-adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age-adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p<0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10years of life (p<0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.

Management of combined massive burn and blast injury: A 20-year experience

IntroductionBlast injuries are complex types of physical trauma resulting from direct or indirect exposure to an explosion, which can be divided into four classes: primary, secondary, tertiary, and quaternary. Primary blast injury results in damage, principally, in gas-containing organs such as the lungs (blast lung injury, BLI). BLI is defined as radiological and clinical evidence of acute lung injury occurring within 12h of exposure to an explosion and not due to secondary or tertiary injury. BLI often combines with cutaneous thermal injury, a type of quaternary blast injury, either in terrorist bomb attacks or in civilian accidental explosions. This report summarizes our experience in the management of combined massive burn and BLI at a Shanghai Burn Center in China. MethodsA retrospective observational analysis of clinical data was performed for massive burn patients with or without BLI during a 20-year interval. Patient characteristics, causes of injury, clinical parameters, management, and outcomes were recorded and evaluated. ResultsA total of 151 patients (120 males and 31 females) with severe burn injury (≥50% TBSA) treated at the Burn Center of Changhai Hospital in Shanghai between July 1997 and June 2017 were enrolled in this study. Their mean age was 38.6±17.8 (3–75) years. Among them, 28 patients had combined BLI and burn injury and 39 patients had no BLI or smoke inhalation injury (non-BLI-SII). No significant difference was observed in the burn area or full-thickness burn area between the two groups. The lowest PaO2/fraction of inspired oxygen (FiO2) ratio during the first 24h in BLI patients was significantly lower than that in non-BLI-SII patients. Exudative changes were observed by X-ray radiography in all BLI patients but not in non-BLI-SII patients within 6h after injury. A significantly higher proportion of colloids were used for fluid resuscitation in BLI patients than that in non-BLI-SII patients. A higher proportion and longer time of mechanical ventilation were needed for BLI patients than those for non-BLI-SII patients, and a higher proportion of patients received sedative agents in the BLI group than those in the non-BLI-SII group. The first escharectomy was performed relatively later in BLI patients than in non-BLI-SII patients because of more time taken by BLI patients to recover from lung injury. The length of ICU and hospital stay in BLI patients was significantly longer than that in non-BLI-SII patients. No significant difference in the overall mortality was detected between these two groups. ConclusionIt is a formidable challenge for clinicians to diagnose and manage massive burn patients combined with BLI. A comprehensive treatment approach is strongly recommended, including fluid resuscitation, airway management, mechanical ventilation, and surgical treatment. Given the high mortality of massive burn patients combined with BLI even in a recognized burn center, more prospective studies are encouraged to assess more effective strategies for the treatment of such patients.

Computation of Cigarette Smoke Exposure Metrics From Breathing.

Traditional metrics of smoke exposure in cigarette smokers are derived either from self-report, biomarkers, or puff topography. Methods involving biomarkers measure concentrations of nicotine, nicotine metabolites, or carbon monoxide. Puff-topography methods employ portable instruments to measure puff count, puff volume, puff duration, and inter-puff interval. In this article, we propose smoke exposure metrics calculated from the breathing signal and describe a novel algorithm for the computation of these metrics. The Personal Automatic Cigarette Tracker v2 (PACT-2) sensors, puff topography devices (CReSS), and video observation were used in a study of 38 moderate to heavy smokers in a controlled environment. Parameters of smoke inhalation including the start and end of each puff, inhale and exhale cycle, and smoke holding were computed from the breathing signal. From these, the traditional metrics of puff duration, inhale-exhale cycle duration, smoke holding duration, inter-puff interval, and novel Respiratory Smoke Exposure Metrics (RSEMs) such as inhale-exhale cycle volume, and inhale-exhale volume over time were calculated. The proposed RSEM algorithm to extract smoke exposure metrics named generated interclass correlations (ICCs) of 0.85 and 0.87 and Pearson's correlations of 0.97 and 0.77 with video observation and CReSS, respectively, for puff duration. Similarly, for the inhale-exhale duration, an ICC of 0.84 and Pearson's correlation of 0.81 was obtained with video observation. The RSEMs provided measures previously unavailable in research that are proportional to the depth and duration of smoke inhalation. The results suggest that the breathing signal may be used to compute smoke exposure metrics.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study

BackgroundThe use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored.MethodsWe conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models.ResultsAmong 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively.ConclusionHydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation.Trial registrationClinicalTrials.gov, NCT03558646

Firefighter's Acute Inflammatory Response to Wildfire Suppression.

The purpose of this study was to determine the inflammatory response to a 12-hour wildfire suppression shift, in firefighters attending the "Black Saturday" natural disaster. Thirty-eight male volunteer firefighters provided venous blood samples before and after a 12-hour firefighting shift. Pre- to post-shift changes in pro-inflammatory (Interleukin [IL]-1β, IL-2, IL-6, IL-8, IL-12P70, granulocyte macrophage-colony stimulating factor [GM-CSF], tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFNγ]), and anti-inflammatory (IL-4, IL-5, IL-7, IL-10, IL-13) cytokines were measured with paired sample t tests, or Wilcoxon t tests for non-parametric data. Interleukin (IL)-6 (P = 0.003) and IL-8 (P = 0.017) were significantly increased following 12-hours of wildfire suppression. There was also a significant decrease in IL-10 (P = 0.021). The observed acute inflammatory response may have resulted from multiple stressors including physical exertion, thermal strain, or smoke inhalation experienced during the shift, and may be a necessary response for the body to adapt to stressor exposure.

Association of biomass fuel smoke with respiratory symptoms among children under 5 years of age in urban areas: results from Bangladesh Urban Health Survey, 2013

BackgroundLittle is known regarding the effect of exposure to biomass fuel smoke inhalation on respiratory symptoms in the Bangladeshi population which is a major health hazard in most of the developing countries. This study aims to explore the association between respiratory symptoms and biomass fuel smoke exposure among children under 5 years of age.MethodsData were extracted from the Bangladesh Urban Health Survey conducted in 2013. A total of 10,575 mothers with at least one surviving children were selected. Respiratory symptoms among children under 5 years of age were considered as the primary outcome. Sequential multiple logistic regression models were used to observe the association between respiratory symptoms and biomass fuel smoke exposure adjusting the effect of residential factors and mother and child characteristics.ResultsAround 40% of the mothers exclusively used biomass fuel irrespective of the kitchen location and 54% of them were habituated in indoor cooking. The prevalence of respiratory symptoms of under-five children among in-house and outdoor biomass fuel users was 23.0% and 21.9%, respectively. Results of fitted multiple logistic regression models showed that the odds of having respiratory symptoms among children under 5 years of age were increased due to in-house biomass fuel use [OR = 1.18; 95% CI, 1.04–1.36] compared with the non-biomass user. An increased risk of respiratory symptoms was also significantly associated with mother’s birth complication [OR = 1.51; 95% CI, 1.36–1.67], non-government organization (NGO) membership of mothers [OR = 1.32; 95% CI, 1.16–1.51], age of the child (6–23m) [OR = 1.29; 95% CI, 1.10–1.52], and nutritional status (stunting) [OR = 1.18; 95% CI, 1.06–1.31].ConclusionThis study found the use of in-house biomass fuel as a significant risk factor associated with respiratory symptoms of children under 5 years of age. More longitudinal studies should be designed to establish a causal relationship between HAP (household air pollution) and respiratory symptoms among children with more direct measures of HAP and clinical procedure.

Medical Event Management for Future Deep Space Exploration Missions to Mars

BackgroundLong-duration exploration missions (LDEMs), such as voyages to Mars, will present unique medical challenges for astronaut crews, including communication delays and the inability to return to Earth early. Medical events threaten crewmember lives and increase the risk of mission failure. Managing a range of potential medical events will require excellent technical and nontechnical skills (NTSs). We sought to identify medical events with potential for rescue, range them according to the potential impact on crew health and mission success during LDEMs, and develop a list of NTSs to train for management of in-flight medical events. Materials and methodsTwenty-eight subject matter experts with specializations in surgery, medicine, trauma, spaceflight operations, NTS training, simulation, human factors, and organizational psychology completed online surveys followed by a 2-d in-person workshop. They identified and rated medical events for survivability, mission impact, and impact of crewmember NTSs on outcomes in space. ResultsSudden cardiac arrest, smoke inhalation, toxic exposure, seizure, and penetrating eye injury emerged as events with the highest potential mission impact, greatest potential for survival, and that required excellent NTS for successful management. Key NTS identified to target in training included information exchange, supporting behavior, communication delivery, and team leadership/followership. ConclusionsWith a planned Mars mission on the horizon, training countermeasures need to be developed in the next 3-5 y. These results may inform policy, selection, medical system design, and training scenarios for astronauts to manage in-flight medical events on LDEMs. Findings may extend to surgical and medical care in any rural and remote location.

Effects of cigarette smoke on barrier function and tight junction proteins in the bronchial epithelium: protective role of cathelicidin LL-37

BackgroundAirway epithelial barrier function is maintained by the formation of tight junctions (TJs) and adherens junctions (AJs). Inhalation of cigarette smoke causes airway epithelial barrier dysfunction and may contribute to the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). We assessed the effects of cigarette smoke on barrier function and expression of multiple TJ and AJ proteins in the bronchial epithelium. We also examined whether treatment with glucocorticosteroids (GCSs), long-acting β2-agonists (LABAs), and human cathelicidin LL-37 can protect against cigarette smoke extract (CSE)-induced barrier dysfunction.MethodsCalu-3 cells cultured at the air-liquid interface were pretreated with or without GCSs, LABAs, GCSs plus LABAs, or LL-37, and subsequently exposed to CSE. Barrier function was assessed by transepithelial electronic resistance (TEER) measurements. Gene and protein expression levels of TJ and AJ proteins were analyzed by quantitative PCR and western blotting, respectively. Immunofluorescence staining of TJ and AJ proteins was performed.ResultsCSE decreased TEER and increased permeability in a concentration-dependent manner. CSE suppressed gene expression of claudin-1, claudin-3, claudin-4, claudin-7, claudin-15, occludin, E-cadherin, junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) within 12 h post-CSE exposure, while suppressed protein expression levels of occludin at 12 h. CSE-treated cells exhibited discontinuous or attenuated immunostaining for claudin-1, claudin-3, claudin-4, occludin, ZO-1, and E-cadherin compared with untreated cells. GCS treatment partially restored CSE-induced TEER reduction, while LABA treatment had no effect. GCS and LABA combination treatment had no additive effect on CSE-induced TEER reduction and gene suppression of TJ and AJ proteins. Human cathelicidin LL-37 counteracted CSE-induced TEER reduction and prevented disruption of occludin and ZO-1. LL-37 also attenuated CSE-induced decreases in gene and protein expression levels of occludin.ConclusionsCSE caused airway epithelial barrier dysfunction and simultaneously downregulated multiple TJ and AJ proteins. GCS and LABA combination treatment had no additive effect on CSE-induced TEER reduction. LL-37 counteracted CSE-induced TEER reduction and prevented disruption of occludin and ZO-1. Use of LL-37 to counteract airway epithelial barrier dysfunction may have significant benefits for respiratory diseases such as asthma and COPD.

Modulation of Peroxynitrite Reduces Norepinephrine Requirements in Ovine MRSA Septic Shock.

Vascular hypo-responsiveness to vasopressors during septic shock is a challenging problem. This study is to test the hypothesis that reactive nitrogen species (RNS), such as peroxynitrite, are major contributing factors to vascular hypo-responsiveness in septic shock. We hypothesized that adjunct therapy with peroxynitrite decomposition catalyst (PDC) would reduce norepinephrine requirements in sepsis resuscitation. Fourteen female Merino sheep were subjected to a "two-hit" injury (smoke inhalation and endobronchial instillation of live methicillin-resistant Staphylococcus aureus [1.6-2.5 × 10 CFUs]). The animals were randomly allocated to control: injured, fluid resuscitated, and titrated norepinephrine, n = 7; or PDC: injured, fluid resuscitated, titrated norepinephrine, and treated with PDC, n = 7. One-hour postinjury, an intravenous injection of PDC (0.1 mg/kg) was followed by a continuous infusion (0.04 mg/kg/h). Titration of norepinephrine started at 0.05 mcg/kg/min based on their mean arterial pressure. All animals were mechanically ventilated and monitored in the conscious state for 24 h. The mean arterial pressure was well maintained in the PDC with significantly less norepinephrine requirement from 7 to 23 h after injury compared with control. Total norepinephrine dose, the highest norepinephrine rate, and time on norepinephrine support were also significantly lower in PDC. Modified sheep organ failure assessment scores at 6 to 18 h postinjury were significantly lower in PDC compared with control. PDC improved survival rate at 24 h (71.4% vs. 28.6%). PDC treatment had no adverse effects. In conclusion, the modulation of RNS may be considered an effective adjunct therapy for septic shock, in the case of hypo-responsiveness to norepinephrine.

Probiotic Administration Increases Mandibular Bone Mineral Density on Rats Exposed to Cigarette Smoke Inhalation.

Smoking is one of the main risk factor for periodontal disease, increasing its prevalence and severity. Probiotics emerged as an alternative for the prevention and treatment of many diseases, since it can modulate the host immune response and modify the modify the microbiome. Therefore, the aim of the present study is to evaluate the effects of probiotic administration on the periodontal tissues in rats exposed to cigarette smoke inhalation (CSI). Forty rats were allocated into the following groups (n=10): group C (control, without CSI and probiotic); group PROB (control+probiotic); group CSI (CSI) and group CSI+PROB (CSI+probiotic). Groups PROB and CSI+PROB received 2g of an association of probiotic microorganisms incorporated into the feed during 6 months. Groups CSI and CSI+PROB were exposed to CSI for 60 min daily. After six months all the animals were euthanized and the hemi-mandibles were collected and processed for microcomputed tomography analyses. Regarding the body weight of the animals, feed consumption was similar among the groups, however, after the second month groups C and PROB showed higher body weight gain when compared to groups CSI and CSI+PROB (p<0.05). Group CSI presented reduced bone mineral density (BMD), whereas group PROB showed the highest values (p=0.01). It can be concluded that administration of probiotics promoted an increase in BMD and, consequently, a protective effect on the mandibular bone structures in rats exposed to inhalation of cigarette smoke.

Pharmacokinetic and Pharmacodynamic Characterization of Tetrahydrocannabinol-Induced Cannabinoid Dependence After Chronic Passive Cannabis Smoke Exposure in Rats.

Introduction: Cannabis is the most widely used illicit drug in the US, and cannabis use among young adults continues to rise. Previous studies have shown that chronic administration of delta 9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, induces dependence in animal models. Because smoking is the most frequent route of THC self-administration, it is critical to investigate the effects of cannabis smoke inhalation. The goal of the current study was to develop a rat model to characterize the pharmacokinetics (PKs) of THC after cannabis smoke inhalation, and to determine if chronic cannabis smoke inhalation leads to the development of cannabis dependence. Materials and Methods: For the PK study, male Wistar rats were administered THC intravenously (1 mg/kg) or exposed to smoke from 5 or 10 sequentially smoked cannabis cigarettes (5.3% THC) in an automated smoking machine. Plasma samples were collected from 10 min to 10 hours post smoke exposure (or intravenous administration) and analyzed using liquid chromatography-mass spectrometry to characterize the PK of THC. A three-compartment PK model was used to characterize the PKs. In a separate study, three groups of male Wistar rats were trained in an intracranial self-stimulation (ICSS) procedure, and exposed to smoke from burning 5 or 10 cannabis cigarettes (or clean air control conditions), 5 days/week for 4 weeks. Discussion and Conclusions: Across exposure days, the change from baseline in ICSS thresholds for cannabis smoke-exposed groups was significantly lower and response latencies were significantly faster in the cannabis smoke-exposed groups compared to controls, suggesting that chronic cannabis smoke exposure has rewarding properties. Acute administration of the CB1 receptor antagonist rimonabant (0.3, 1.0, 3.0 mg/kg) induced a dose-dependent increase in ICSS thresholds in the smoke-exposed rats, suggestive of dependence and withdrawal. Finally, an effect compartment PK-pharmacodynamic model was used to describe the relationship between THC concentrations and changes in ICSS thresholds after cannabis smoke exposure.

Cigarette smoke inhalation aggravates diabetic kidney injury in rats.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg-1). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L-1), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.