n-3 Polyunsaturated Fatty Acids Modulate LPS-Induced ARDS and the Lung-Brain Axis of Communication in Wild-Type versus Fat-1 Mice Genetically Modified for Leukotriene B4 Receptor 1 or Chemerin Receptor 23 Knockout.

Specialized pro-resolving mediators (SPMs) and especially Resolvin E1 (RvE1) can actively terminate inflammation and promote healing during lung diseases such as acute respiratory distress syndrome (ARDS). Although ARDS primarily affects the lung, many ARDS patients also develop neurocognitive impairments. To investigate the connection between the lung and brain during ARDS and the therapeutic potential of SPMs and its derivatives, fat-1 mice were crossbred with RvE1 receptor knockout mice. ARDS was induced in these mice by intratracheal application of lipopolysaccharide (LPS, 10 µg). Mice were sacrificed at 0 h, 4 h, 24 h, 72 h, and 120 h post inflammation, and effects on the lung, liver, and brain were assessed by RT-PCR, multiplex, immunohistochemistry, Western blot, and LC-MS/MS. Protein and mRNA analyses of the lung, liver, and hypothalamus revealed LPS-induced lung inflammation increased inflammatory signaling in the hypothalamus despite low signaling in the periphery. Neutrophil recruitment in different brain structures was determined by immunohistochemical staining. Overall, we showed that immune cell trafficking to the brain contributed to immune-to-brain communication during ARDS rather than cytokines. Deficiency in RvE1 receptors and enhanced omega-3 polyunsaturated fatty acid levels (fat-1 mice) affect lung-brain interaction during ARDS by altering profiles of several inflammatory and lipid mediators and glial activity markers.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Luteolin attenuates lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome by activating alveolar epithelial sodium channels via cGMP/PI3K pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Luteolin (Lut) was recently identified as the major active ingredient of Mosla scabra, which was a typical representative traditional Chinese medicine and had been used to treat pulmonary diseases for thousands of years. AIM OF THE STUDY: This study was to explore the effects and relative mechanisms of Lut in LPS-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The main characteristic of ALI/ARDS is pulmonary edema, and epithelial sodium channel (ENaC) is a key factor in effective removal of excessive alveolar edematous fluid, which is essential for repairing gas exchange and minimizing damage to the peripheral tissues. However, whether the therapeutic effects of Lut on respiratory diseases are relative with ENaC is still unknown. MATERIALS AND METHODS: Alveolar fluid clearance was calculated in BALB/c mice and ENaC function was measured in H441 cells. Moreover, ENaC membrane protein and mRNA were detected by Western blot and real-time PCR, respectively. We also studied the involvement of cGMP/PI3K pathway during the regulation of Lut on ENaC during LPS-induced ALI/ARDS by ELISA method and applying cGMP/PI3K inhibitors/siRNA. RESULTS: The beneficial effects of Lut in ALI/ARDS were evidenced by the alleviation of pulmonary edema, and enhancement of both amiloride-sensitive alveolar fluid clearance and short-circuit currents. Lut could alleviate the LPS decreased expression levels of ENaC mRNA and membrane protein in H441 cells and mouse lung. In addition, cGMP concentration was increased after the administration of Lut in ALI/ARDS mice, while the inhibition of cGMP/PI3K pathway could abrogate the enhanced AFC and ENaC protein expression of Lut. CONCLUSION: These results implied that Lut could attenuate pulmonary edema via enhancing the abundance of membrane ENaC at least partially through the cGMP/PI3K pathway, which could provide a promising therapeutic strategy for treating ALI/ARDS.

Hypoxic respiratory distress potentially secondary to phosphorus trifluoride gas exposure.

We herein report a rare, probable exposure of a patient to phosphorus trifluoride gas. The objective of this case report is to highlight the potential exposure to phosphorus trifluoride gas and discuss the best management of it. A 48-year-old worker at a specialty gases laboratory was transported to the community Emergency Department (ED) in respiratory distress, presenting with peripheral cyanosis, an unobtainable oxygen saturation, chocolate-colored blood, and a Glasgow coma scale of 15. A non-rebreather was placed, poison control was contacted, and the patient was administered empiric methylene blue intravenously due to worsening cyanosis and respiratory distress. Upon arrival at the academic facility, the patient was no longer cyanotic and reported improvement of his symptoms. The patient's employer informed staff that a canister of phosphorus trifluoride gas in his workstation was found to be empty but should have been full. It was also discovered that a coworker left work early the same day with similar but milder symptoms. Hyperbaric oxygen therapy was considered; however, the patient was improving on oxygen via non-rebreather, and he had no other indications. Because the patient continued to require supplemental oxygen to maintain their oxygen saturation above 92%, he was admitted to the ICU and treated with prednisone daily for chemical pneumonitis. After 4 days, he successfully transitioned to room air without hypoxia. While exposures such as this do not occur frequently, it is important to maintain a broad differential and treatment plan as we continue to investigate the etiology and best treatment option.

iRGD conjugated nimbolide liposomes protect against endotoxin induced acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a deadly respiratory illness associated with refractory hypoxemia and pulmonary edema. The recent pandemic outbreak of COVID-19 is associated with severe pneumonia and inflammatory cytokine storm in the lungs. The anti-inflammatory phytomedicine nimbolide (NIM) may not be feasible for clinical translation due to poor pharmacokinetic properties and lack of suitable delivery systems. To overcome these barriers, we have developed nimbolide liposomes conjugated with iRGD peptide (iRGD-NIMLip) for targeting lung inflammation. It was observed that iRGD-NIMLip treatment significantly inhibited oxidative stress and cytokine storm compared to nimbolide free-drug (f-NIM), nimbolide liposomes (NIMLip), and exhibited superior activity compared to dexamethasone (DEX). iRGD-NIMLip abrogated the LPS induced p65 NF-κB, Akt, MAPK, Integrin ß3 and ß5, STAT3, and DNMT1 expression. Collectively, our results demonstrate that iRGD-NIMLip could be a promising novel drug delivery system to target severe pathological consequences observed in ARDS and COVID-19 associated cytokine storm.

Emodin improves alveolar hypercoagulation and inhibits pulmonary inflammation in LPS-provoked ARDS in mice via NF-κB inactivation.

BACKGROUND: Alveolar hypercoagulation and pulmonary inflammation are important characteristics and they regulate each other in acute respiratory distress syndrome (ARDS). NF-κB pathway has been confirmed to be involved in regulation of this crosstalk. Emodin, a traditional Chinese herb, shows potent inhibitory effect on NF-κB pathway, but whether it is effective in alveolar hypercoagulation and pulmonary inflammation in ARDS remains to be elucidated. PURPOSE: The aim of this experiment was to evaluate the efficacy of emodin on LPS-provoked alveolar hypercoagulation and excessive pulmonary inflammation in ARDS, and its potential mechanism. METHODS: Mice ARDS was set up through LPS (40 µl, 4 mg/ml) inhalation. Male mice were randomly received with BPS, LPS only, LPS+ emodin (5 mg/kg, 10 mg/kg, 20 mg/kg, respectively) and BAY65-1942, an inhibitor of IKKß. After 48 h of LPS stimulation, pulmonary pathological injury, expressions of Tissue factor (TF), plasminogen activator inhibitor (PAI)-1, activated protein C (APC), collagen Ⅰ, collagen III, interleukin (IL) 8, IL-1ß and tumor necrosis factor (TNF)-α in lung tissues, as well as concentrations of antithrombin III (AT III), procollagen peptide type III (PIIIP), soluble thrombomodulin (sTM), thrombin antithrombin complex (TAT), myeloperoxidase (MPO) and the percentage of inflammatory cells in bronchoalveolar lavage fluid (BALF) were all determined. NF-κB pathway activation as well as NF-κB DNA binding activity in pulmonary tissue were simultaneously checked. RESULTS: LPS stimulation resulted in obvious lung injury, excessive inflammatory cells infiltration, which all were dose-dependently ameliorated by emodin. Expressions of TF, PAI-1, collagen Ⅰ and collagen III as well as IL-8, IL-1ß and TNF-α in pulmonary tissue were all elevated while APC decreased under LPS provocation, which were all reversed by emodin treatment in dose-dependent manner. LPS promoted the secretions of PIIIP, sTM, TAT and inhibited AT III production in BALF, and resulted in high levels of MPO and the percentage of inflammatory cells in BALF, all of which were significantly and dose-dependently attenuated while AT III production was increased by emodin. Meanwhile, emodin effectively inhibited NF-κB pathway activation and attenuated p65 DNA binding activity induced by LPS inhalation. Emodin and BAY-65-1942 had similar impacts in this experiment. CONCLUSIONS: Emodin improves alveolar hypercoagulation and fibrinolytic inhibition and depresses excessive pulmonary inflammation in ARDS mice in dose-dependent manner via NF-κB inactivation. Our data demonstrate that emodin is expected to be an effective drug in alveolar hypercoagulation and pulmonary inflammation in ARDS.

Acupoint Catgut Embedding Improves the Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: This study investigated the potential therapeutic effects of acupoint catgut embedding (ACE) at ST36 and BL13 on lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into the normal saline (NS group with a sham procedure), lipopolysaccharide (LPS group with a sham procedure), and LPS plus ACE (LPS+ACE with ACE at bilateral BL13 and ST36 acupoints one day before LPS injection) groups. After intratracheal instillation of normal saline or LPS (0.5 mg/kg), all rats were subjected to mechanical ventilation for 4 h. Their blood gas was analyzed before and after lung injury, and their lung pressure-volumes were measured longitudinally. The levels of TNF-α, IL-6, IL-10, and phosphatidylcholine (PC) and total proteins (TP) in bronchial alveolar lavage fluid (BALF) were assessed. Their wet to dry lung weight ratios, histology, myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were measured. Their lung aquaporin 1 (AQP1) and Occludin protein levels were analyzed. RESULTS: LPS administration significantly decreased the ratios of PaO2/FiO2 and pressure-volumes and induced lung inflammation and injury by increased concentrations of TNF-α, IL-6, IL-10, and TP in BALF and MPO and MDA in the lung but decreased PC in BALF and SOD activity in the lungs. LPS also reduced AQP1 and Occludin protein levels in the lung of rats. In contrast, ACE significantly mitigated the LPS-induced lung injury, inflammation, and oxidative stress and preserved the AQP1 and Occludin contents in the lung of rats. CONCLUSIONS: ACE significantly improved respiratory function by mitigating inflammation and oxidative stress and preserving AQP1 and Occludin expression in the lung in a rat model of LPS-induced ARDS.

Oral administration of Ulmus davidiana extract suppresses interleukin-1ß expression in LPS-induced immune responses and lung injury.

BACKGROUND: Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood. OBJECTIVE: The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models. METHODS: RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed. RESULTS: LPS infusion resulted in elevated IL-1ß mRNA expression, nitrite levels, TNF-α expression, and IL-1ß expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity. CONCLUSIONS: The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1ß mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.

[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.

Cleistanthus collinus poisoning: a case report of intentional poisoning.

We report a case of 50-year-old male patient from tribal area in South Indian state of Telangana, who ingested the liquid extract from crushed leaves of the plant, cleistanthus collinius with the intention of self-harm. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on arterial blood gas (ABG) and was corrected accordingly. On second day of admission he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of acute respiratory distress syndrome (ARDS). The patient had to be intubated. Continuous renal replacement therapy (CRRT) was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient succumbed to illness. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on ABG and was corrected accordingly. On second day of admission, he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of ARDS. The patient had to be intubated on day 2. CRRT was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient gradually deteriorated, had cardiac arrest and passed away on day 5 of his hospital stay.

Ex vivo lung perfusion as a human platform for preclinical small molecule testing.

The acute respiratory distress syndrome (ARDS) causes an estimated 70,000 US deaths annually. Multiple pharmacologic interventions for ARDS have been tested and failed. An unmet need is a suitable laboratory human model to predictively assess emerging therapeutics on organ function in ARDS. We previously demonstrated that the small molecule BC1215 blocks actions of a proinflammatory E3 ligase-associated protein, FBXO3, to suppress NF-κB signaling in animal models of lung injury. Ex vivo lung perfusion (EVLP) is a clinical technique that maintains lung function for possible transplant after organ donation. We used human lungs unacceptable for transplant to model endotoxemic injury with EVLP for 6 hours. LPS infusion induced inflammatory injury with impaired oxygenation of pulmonary venous circulation. BC1215 treatment after LPS rescued oxygenation and decreased inflammatory cytokines in bronchoalveolar lavage. RNA sequencing transcriptomics from biopsies taken during EVLP revealed robust inflammatory gene induction by LPS with a strong signal for NF-κB-associated transcripts. BC1215 treatment reduced the LPS induction of genes associated with inflammatory and host defense gene responses by Gene Ontology (GOterm) and pathways analysis. BC1215 also significantly antagonized LPS-mediated NF-κB activity. EVLP may provide a unique human platform for preclinical study of chemical entities such as FBXO3 inhibitors on tissue physiology.

Lycium barbarum polysaccharide protects against LPS-induced ARDS by inhibiting apoptosis, oxidative stress, and inflammation in pulmonary endothelial cells.

Acute respiratory distress syndrome (ARDS) is a heterogenous syndrome characterised by diffuse alveolar damage, with an increase in lung endothelial and epithelial permeability. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses antiapoptotic and antioxidative effects in distinct situations. In the present study, the protective effects and potential molecular mechanisms of LBP against lipopolysaccharide (LPS)-induced ARDS were investigated in the mice and in the human pulmonary microvascular endothelial cells (HPMECs). The data indicated that pretreatment with LBP significantly attenuated LPS-induced lung inflammation and pulmonary oedema in vivo. LBP significantly reversed LPS-induced decrease in cell viability, increase in apoptosis and oxidative stress via inhibiting caspase-3 activation and intracellular reactive oxygen species (ROS) production in vitro. Moreover, the scratch assay verified that LBP restored the dysfunction of endothelial cells (ECs) migration induced by LPS stimulation. Furthermore, LBP also significantly suppressed LPS-induced NF-κB activation, and subsequently reversed the release of cytochrome c. These results showed the antiapoptosis and antioxidant LBP could partially protect against LPS-induced ARDS through promoting the ECs survival and scavenging ROS via inhibition of NF-κB signalling pathway. Thus, LBP could be potentially used for ARDS against pulmonary inflammation and pulmonary oedema.

Paraquat poisoning: Acute lung injury - a missed diagnosis.

Paraquat is a herbicide of great toxicological importance because it is associated with high mortality rates, mainly due to respiratory failure. We report the case of a 28-year-old man admitted to the casualty department at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance, later identified as paraquat, together with an unknown amount of alcohol, in a suicide attempt. He developed respiratory distress associated with lung parenchymal infiltrates that required ventilatory support and later a spontaneous pneumothorax, and died in the intensive care unit. We discuss the importance of a high index of suspicion of paraquat poisoning in rural areas, where paraquat is readily available as a herbicide on farms, in patients with a similar presentation. We further stress the importance of identifying the classic radiological progression after paraquat poisoning, to help avoid a delay in diagnosis if the culprit substance is not known (as happened in our case). Lastly, we look at the importance of avoiding oxygen supplementation, and early administration of immunosuppressive therapy, to improve outcome.

Hydroxysafflor Yellow A Alleviates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Mice.

Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L. The present study investigated the protective effect of HSYA on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in mice, and the underlying mechanisms involved. HSYA (14, 28, 56 mg/kg) was intraperitoneally injected to mice once daily from day 1 to 10 after LPS administration. HSYA attenuated the body weight loss, the augmented left index and the increase of pathologic changes in pulmonary inflammation caused by LPS. Treatment with HSYA also alleviated increased expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß1, collagen (Col) I, Col III, α-smooth muscle actin (α-SMA), myeloid differentiation (MD)-2, Toll-like receptor 4 (TLR4) and cluster differentiation (CD)14 at the mRNA (RT-PCR) and protein levels (Western blot and enzyme-linked immuno sorbent assay). Moreover, HSYA inhibited the elevated levels of nuclear factor (NF)-κB and α-SMA in lung tissue (immunohistochemistry), and alleviated the slight collagen deposition in pulmonary tissues (Masson's trichrome staining). HSYA inhibited the specific binding of fluorescein isothiocyanate (FITC)-LPS on human lung epithelial cell line (A549) or human umbilical vein cell line (Eahy926) cells (flow cytometry). These findings suggested that HSYA has a protective effect on acute respiratory distress syndrome (ARDS) induced by LPS through blocking the TLR4/NF-κB pathway, and that the TLR4 receptor might be a target of HSYA on the cell membrane.

The Protective Effects of HJB-1, a Derivative of 17-Hydroxy-Jolkinolide B, on LPS-Induced Acute Distress Respiratory Syndrome Mice.

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, there is a tremendous need for new therapies. We have reported that HJB-1, a 17-hydroxy-jolkinolide B derivative, exhibited strong anti-inflammatory effects in vitro. In this study, we investigated its impacts on LPS-induced ARDS mice. We found that HJB-1 significantly alleviated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNF-α, IL-1ß and IL-6 in BALF. In addition, HJB-1 markedly suppressed LPS-induced IκB-α degradation, nuclear accumulation of NF-κB p65 subunit and MAPK phosphorylation. These results suggested that HJB-1 improved LPS-induced ARDS by suppressing LPS-induced NF-κB and MAPK activation.

Barium sulfate aspiration: Severe chemical pneumonia induced by a massive reflux of contrast medium during small bowel barium enema.

Barium contrast radiography is a conventional procedure aimed at revealing lesions of the alimentary tract using barium sulfate on X-ray irradiation. Although it is widely used in clinics, adverse effects and complications are observed, such as anaphylaxis, granuloma, fecalithes, abdomen-leaking, embolism, bacterial contamination, and aspiration. We report a case of death due to a massive barium sulfate aspiration resulted from an air-barium double contrast enema radiography. A 25-year-old female patient was hospitalized with symptoms of abdominal distention, nausea, vomiting and diarrhea for three days. A progressive respiratory distress presented only 1h after a small bowel air-barium double contrast enema. The patient died 11h later. The result of autopsy revealed the cause of death to be severe chemical pneumonitis induced by gastric fluid which was aspirated into her lungs. Barium sulfate is generally recognized to be chemically inert for the respiratory system, but a mixture of barium sulfate with gastric contents is fatal. Here we intend to suggest that, when determining the potential cause of death, medical examiners should consider a patient's status quo as well as the possible adverse effects and complications caused by the barium sulfate preparation during gastrointestinal radiography.

[ARDS after Incidental Aspiration of Petroleum in an Adult]. / ARDS nach akzidentieller Aspiration von Petroleum bei einem Erwachsenen.

Petroleum aspiration as a reason for lipid pneumonia is a rare complication. Mostly children are affected and mortality rates are low. In most case series, virtually every subject survived.We describe here the case of a patient who developed ARDS and pneumatoceles with a fatal outcome. Due to the undulant nature of the disease, multipe thoracic CT were performed, enabling us to describe the precise radiologic course of the disease.

Epidemic dropsy: case report and the morphologic features in a patient who died at Tikur Anbessa Specialized Hospital.

Epidemic dropsy results from the consumption of edible oils adulterated with argemone mexicana oil. In a 2008 epidemic in Addis Ababa five patients died and in one of these a partial autopsy has been performed. The clinical impression of acute respiratory distress syndrome has been confirmed by the demonstration of massive diffuse alveolar damage. These features are consistent with findings reported in similar epidemics.

No additive effects of inhaled iloprost and prone positioning on pulmonary hypertension and oxygenation in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary hypertension is associated with a poor prognosis. Prone position is effective to improve oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However, combination of these interventions has not been examined before. The hypothesis was that this combination had additive effects on oxygenation and pulmonary hemodynamics as compared with each intervention alone. METHODS: In a prospective, randomized cross-over study, ten pigs were anesthetized, intubated and ventilated with volume controlled ventilation. Carotid, jugular venous and pulmonary artery catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg). Measurements were repeated in randomized different sequences of prone or supine positions with or without iloprost inhalation (220 ng/kg/min) (four combinations). Systemic and pulmonary arterial pressures; arterial and mixed venous blood gases; and Qs/Qt and the resistances were recorded. RESULTS: Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine (37±10 vs. 31±8 mmHg; P<0.05) and prone positions (38±9 vs. 29±8 mmHg; P<0.05); but did not obtain a significant improvement in oxygenation in both positions. Prone position improved the oxygenation (p<0.0001) compared to supine position in both with (361±140 vs. 183±158 mmHg, P<0.05) or without iloprost application (331±112 vs. 167±117 mmHg, P<0.05); but did not achieve a significant decrease in MPAP. CONCLUSION: Although iloprost reduced pulmonary arterial pressures, and prone positioning improved oxygenation; there are no additive effects of the combination of both interventions on both parameters. To treat both pulmonary hypertension and hypoxemia, application of iloprost in prone position is suggested.

[Effects of baicalin on pulmonary functions of acute respiratory distress syndrome induced by oleic acid in rats].

OBJECTIVE: To investigate the effect of baicalin on pulmonary functions and its mechanism during the development of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. METHODS: Rats were randomized into 5 groups: control, ARDS (OA induction, 0.12 mg/kg), baicalin-treated group (150 mg/kg), baicalin-treated group (300 mg/kg) and baicalin-treated group (450 mg/kg). The blood samples and lung tissue were collected at 10 min, 1, 2 and 6 h after OA injection. The lung concentration of myeloperoxidase (MPO) was detected by an ELISA (enzyme-linked immunosorbent assay) kit. Meanwhile, blood gas analysis and pulmonary pathological examination were also performed. RESULTS: The level of arterial oxygen partial pressure and oxygenation index decreased (P < 0.01 vs. control) and oxygenation index (190 mm Hg, 1 mm Hg = 0.133 kPa) reached the diagnostic standard of ARDS at 2 h in ARDS group. In baicalin-treated group (150 mg/kg and 300 mg/kg), the level of arterial oxygen partial pressure and oxygenation index increased versus the ARDS group. In baicalin-treated group (450 mg/kg), the level of arterial oxygen partial pressure was undifferentiated at 1, 2 and 6 h (P > 0.05) and decreased at 10 min (46.8 mm Hg, P < 0.05) versus the ARDS group. The level of MPO increased in baicalin-treated (300 mg/kg) and ARDS groups. Compared with the ARDS group, the level of MPO decreased significantly in baicalin-treated group (300 mg/kg) at 10 min, 1 and 2 h. Meanwhile, the pulmonary pathological damage improved in baicalin-treated group (300 mg/kg). CONCLUSION: An appropriate dose of baicalin may improve hypoxemia of ARDS induced by OA in rats. It may be due to the inhibition of MPO activity.