Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation.

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy.

Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.

Unusual location of the glomus tumour in the liver: A case report and literature review.

RATIONALE: Liver glomus tumor is very rare, and only 6 cases have been reported. Herein, we report another case of liver glomus tumor and the clinicopathological features are summarized. PATIENT CONCERNS: An 18-year-old male patient was admitted due to hypertension and arrhythmia for 4 days. DIAGNOSES: Abdominal enhanced CT revealed a 6.0-cm solid and cystic mass in the left liver lobe. The mass was collected by hepatic lobectomy. Microscopically, the tumor cells were round or oval, and had no malignant features and no evident atypia. Immumohistochemically, tumor cells were positive for positive for SMA and vimentin, but partially positive for syn, CD34 and desmin. He was pathologically diagnosed with liver glomus tumor. INTERVENTIONS: The patient underwent a left hepatic lobectomy. OUTCOMES: After surgery, this patient was followed up for 6 months, and metastasis/recurrence was not observed. LESSONS: Primary liver glomus tumor has no specific clinical manifestations, and imaging examinations have limitations for its diagnosis. Immunostaining for SMA and vimentin is necessary to prove the diagnosis. Complete resection is strongly advised and it has a favorable prognosis.

Macrophage polarization is related to the pathogenesis of decompression induced lung injury.

Studies have shown that blood bubbles may be detectable and there is ultrasonic evidence of acute interstitial lung edema even after diving without protocol violation. Macrophages play a central role in the inflammation, and macrophage polarization is closely related to the pathogenesis some lung diseases. Available findings indicate that decompression may induce the production of pro-inflammatory cytokines, chemokines, and adhesion molecules in the blood and tissues, which are associated with the macrophage polarization, and hyperbaric treatment may exert therapeutic effects on decompression related diseases via regulating these factors. Thus, we hypothesize that the polarization of circulating and/or resident macrophages is involved in the pathogenesis of decompression induced lung injury.

Changes in angiotensin II and angiotensin-converting enzyme of different tissues after prolonged hyperoxia exposure.

Current study findings concerning changes in the renin-angiotensin system (RAS) in cases of hyperoxic acute lung injury (HALI) have shown conflicting results. This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly assigned into three groups: the control group, HALI group and hyperbaric oxygen preconditioning (HBO2-PC) group. HALI was induced by exposure to pure oxygen at 250 kPa for six hours. In the HBO2-PC group, rats were exposed to oxygen at 250 kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24 hours after the last oxygen exposure.=After HALI, the lung, spleen and liver were harvested for HE staining and pathological examination. At one hour and 18 hours after HALI, the blood, liver, lung and spleen were collected for the detection of Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological examination showed the lung was significantly damaged and characteristics of HALI were observed, but there were no significant pathological changes in the liver and spleen. After HALI, Ang II and ACE contents of different tissues increased progressively over time, but the HBO2-PC group showed reductions in the Ang II and ACE contents to a certain extent, especially at 18 hours after injury. These findings suggest prolonged hyperoxia exposure may activate the RAS, which may be associated with the pathogenesis of HALI. HBO2-PC has a limited capability to inhibit RAS activation.

Polarization of macrophages in the blood after decompression in mice.

The veins are a major site of bubble formation after decompression and the lung is a target organ of bubbles. Bubble-induced inflammation has been implicated in the pathogenesis of decompression sickness (DCS). Macrophages play a central role in the inflammation, and macrophage polarization is closely related to the pathogenesis of some lung diseases. This study aimed to investigate the blood macrophage polarization in mice after decompression. BALB/c mice were exposed to hyperbaric air for 60 minutes, and rapid decompression was performed to induce DCS. Slow decompression and hyperoxia (150 kPa, 60 minutes) served as control groups, and hyperbaric oxygen (HBO; 250 kPa, 60 minutes) was employed for DCS treatment. Macrophage phenotype was determined by flow cytometry, and cytokines related to macrophage polarization were measured by enzyme-linked immunosorbent assay. Our results showed rapid decompression significantly induced the shift to M1 phenotype, which was not observed in slow decompression group, HBO and hyperoxia groups. These changes were consistent with the change in blood tumor necrosis factor α level. Moreover, any treatment could significantly increase the M2 macrophages, but blood interleukin-10 remained unchanged after different treatments. In addition, the blood and lung levels of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 increased significantly after rapid decompression, but reduced markedly after HBO treatment. Taken together, rapid decompression is able to induce the shift to M1 phenotype in blood macrophages, which may then migrate into the lung involving decompression-induced lung injury.

Nitric oxide and hyperoxic acute lung injury.

Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI.

Application of hyperbaric oxygen in liver transplantation.

In recent years, hyperbaric oxygen (HBO) has been used in the treatment of a lot of diseases such as decompression sickness, arterial gas embolism, carbon dioxide poisoning, soft tissue infection, refractory osteomyelitis, and problematic wound, but little is known about its application in liver transplantation. Although several studies have been conducted to investigate the protective effects of HBO on liver transplantation and liver preservation, there are still some controversies on this issue, especially its immunomodulatory effect. In this short review, we briefly summarize the findings supporting the application of HBO during liver transplantation (including donors and recipients).