benzofurans and Carbon-Monoxide-Poisoning

Approximately 10% to 30% patients develop delayed encephalopathy after acute CO poisoning (DEACMP). No specific treatment is available and poor prognosis is a characteristic of this disease. We aimed to evaluate the efficacy and safety of all therapies that have been tried in randomized controlled trial (RCT) for DEACMP.. We conducted a systematic search of the Cochrane, Embase, PubMed, and Web of Science databases.. Overall, 4 RCTs were identified in our study. Both hyperbaric oxygen (HBO) and mesenchymal stem cell (MSC) transplantation were effective in DEACMP, and MSC seemed to be superior to HBO. The addition of dexamethasone, N-butylphthalide, or XingZhi-YiNao granules into HBO, or butylphthalide into MSC could achieve better neurological recovery in DEACMP patients but did not significantly increase the incidence of adverse events.. Several therapies have shown positive results in treating DEACMP and need to be proven by further studies.

Topics: Benzofurans; Brain Diseases; Carbon Monoxide Poisoning; Dexamethasone; Drugs, Chinese Herbal; Humans; Hyperbaric Oxygenation; Mesenchymal Stem Cell Transplantation; Randomized Controlled Trials as Topic; Time Factors

BACKGROUND Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is one of the most serious complications after CO poisoning. This study was conducted to explore the efficacy of the combined application of N-Butylphthalide and hyperbaric oxygenation therapy (HBO) on cognitive dysfunction in patients with DEACMP. MATERIAL AND METHODS A total of 184 patients with DEACMP were randomly assigned to either receive HBO or N-Butylphthalide and HBO. Meanwhile, all patients received conventional treatment. The total remission rate (RR) was used to assess the clinical efficacy. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function, and the National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological function. RESULTS Finally, there were 90 and 94 patients in the control and experimental groups, respectively. After eight weeks of treatment, the total RR in the experimental group (47.9%) was significantly higher than that in the control group (33.3%). Compared to the control group, significantly more patients in the experimental group had MMSE scores of 24-30. The lower NIHSS score in the experimental group showed that N-Butylphthalide had the effect of preservation and restoration of neurological function. No obvious drug toxicity or liver and kidney dysfunction was observed, and there was no significant change in the level of blood glucose and blood lipids. CONCLUSIONS These results indicated that the combined application of N-Butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DEACMP and have great clinical efficacy, which should be further studied.

Topics: Acute Disease; Benzofurans; Brain Diseases; Carbon Monoxide Poisoning; Cognitive Dysfunction; Demography; Female; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Neuropsychological Tests; Remission Induction; Treatment Outcome

Delayed encephalopathy after carbon monoxide (CO) poisoning (DEACMP) is still a clinical challenge. This study aimed to investigate the efficacy of combined therapy of mesenchymal stem cell (MSC) transplantation and butylphthalide in DEACMP patients.Forty-two DEACMP patients were treated with 1 of the 3 therapies: combined therapy of MSC transplantation and butylphthalide; MSC transplantation alone; or hyperbaric oxygen therapy. The MSCs were alternatively injected into the subarachnoid space and the carotid artery using a self-made high-pressure injector. The Mini-Mental State Examination and the Barthel index of activities of daily living were administered before the treatment, and at 1 month, 3 months, and 6 months after the treatment. Computed tomography and magnetic resonance imaging results before and after the treatment were compared.At 1 month, 3 months, and 6 months after the treatment, the Mini-Mental State Examination scores and the Barthl scores were significantly higher in patients with the combined therapy of MSC transplantation and butylphthalide than those in patients with MSC transplantation alone or hyperbaric oxygen therapy (all P < 0.0001). No significant adverse events occurred.The combination of MSC transplantation and butylphthalide is safe and effective in treating DEACMP.

Topics: Adult; Analysis of Variance; Benzofurans; Brain Diseases; Carbon Monoxide Poisoning; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Mesenchymal Stem Cell Transplantation; Middle Aged; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

Carbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP.. A total of 171 patients with DEACMP were recruited and assigned to the combined therapy group (receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy). Conventional treatments were provided for all patients. The cognition and movement changes in patients were evaluated by the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) before and after the treatment at 1 month, 3 months, and 1 year, respectively.. At 1 month, 3 months, and 1 year after the treatment, the MMSE, MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group. There were no significant alterations in blood glucose, blood lipids, or liver and kidney function during the whole treatment session. Some patients experienced loss of appetite, mild headache and minor skin irritations. However, these patients recovered by themselves and needed no additional medications or special treatment.. These results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the cognitive and motor functions of patients and is very safe.

Topics: Activities of Daily Living; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Benzofurans; Brain Diseases; Carbon Monoxide Poisoning; Combined Modality Therapy; Dexamethasone; Female; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Young Adult

To explore the effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier (BBB) in rats with acute carbon monoxide (CO) poisoning.. A total of 144 adult healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group, CO poisoning group, and NBP treatment group, with 48 rats in each group. The acute CO poisoning model was reproduced in hyperbaric oxygen chamber, and all model rats were given hyperbaric oxygen therapy once daily. The rats in the normal control group were free to breathe fresh air. The rats in NBP treatment group were administered orally NBP 60 mg/kg twice a day at 2 hours after poisoning until death. The rats in normal control group and CO poisoning group were treated with equal amount of pure olive oil. Four rats were sacrificed from each group at 1, 3, 7, 14 days after model reproducing, respectively. The changes in ultrastructure of BBB were observed under transmission electron microscope. The expressions of ZO-1 and claudin-5 proteins were determined by immunofluorescence staining and Western Blot. The localization of the two target proteins was observed by immunofluorescence double staining. The correlation between the two proteins was analyzed by linear regression.. The ultrastructure of BBB was normal in normal control group, some ZO-1 and a large number of claudin-5 positive cells were observed. The ultrastructure of BBB was seriously injured, ZO-1 and claudin-5 positive cells in brain tissue were significantly decreased, and the expressions of ZO-1 and claudin-5 proteins in brain tissue at 1 day after poisoning in CO poisoning group were significantly lower than those of normal control group (ZO-1 protein: 3.38±0.30 vs. 24.50±5.62, claudin-5 protein: 11.38±0.93 vs. 46.35±6.88, both P < 0.05), and although gradually restored, they were maintained at relatively lower levels until 14 days as compared with those in normal control group (ZO-1 protein: 10.35±0.80 vs. 24.63±3.57, claudin-5 protein: 32.35±3.11 vs. 46.43±7.20, both P < 0.05). NBP treatment could significantly alleviate the ultrastructure injury of BBB induced by acute CO poisoning, the amount of ZO-1 and claudin-5 positive cells in brain tissue were significantly increased, as well as the expressions of ZO-1 and claudin-5 proteins were significantly increased, which were significantly higher than those of CO poisoning group from 1 day and 3 days on, respectively (1-day ZO-1 protein: 7.57±0.69 vs. 3.38±0.30, 3-day claudin-5 protein: 20.46±1.42 vs. 11.43±0.86, both P < 0.05), and which showed an increase tendency with time prolongation. The results of immunofluorescence double staining showed that ZO-1 and claudin-5 proteins could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed the positive correlation between the expressions of ZO-1 and claudin-5 proteins in brain tissue of rats with acute CO poisoning (R. NBP could markedly improve the ultrastructure and functional integrity of BBB through up-regulating the expressions of ZO-1 and claudin-5 proteins, and then reduce brain damage caused by CO poisoning.

Topics: Animals; Benzofurans; Blood-Brain Barrier; Carbon Monoxide Poisoning; Claudin-5; Male; Rats; Rats, Sprague-Dawley

Carbon monoxide (CO) intoxication is one of the most common types of poisoning worldwide, and may result in neuropathologic sequelae, yet its pathogenesis is not clear and there is no optimal management strategy for patients with CO poisoning. In this study, the rat model of CO poisoning was established in a hyperbaric chamber by CO exposure. Rats were administered orally N-Butylphthalide (NBP) at a dose of 1 ml/100g. Neuronal apoptosis was assessed by TUNEL stain and flow cytometry. The expressions of neurite outgrowth inhibitor (Nogo), myelin-associated glycoprotein (MAG) and Nogo receptor-1 (NgR1) were observed in rat brain tissue by immunohistochemistry and double immunofluorescence staining. As we expected, CO poisoning could start the mechanism of apoptosis. The number of apoptotic cells and the early neuronal apoptosis percentage (EAR) were significantly increased at 1 day, 3 day after CO exposure. NBP treatment obviously reduce neuronal apoptosis and the EAR (P<0.05). CO poisoning could induce Nogo, MAG and NgR1 expressions. The increased Nogo, MAG and NgR1 proteins were still observed at 4 week after CO poisoning. NBP could significantly reduce the levels of Nogo and NgR1 proteins. Then we suspected that the expressions of Nogo, MAG and NGR1 proteins might be associated with brain injury and demyelination induced by CO poisoning. NBP might inhibit neuronal apoptosis and the EAR, down-regulate the expressions of Nogo and NgR1 proteins (but not MAG), and play a neuro-protective role in brain damage after acute CO poisoning.

Topics: Animals; Apoptosis; Benzofurans; Brain; Carbon Monoxide Poisoning; GPI-Linked Proteins; Male; Myelin Proteins; Myelin-Associated Glycoprotein; Neuroprotective Agents; Nogo Proteins; Nogo Receptor 1; Rats, Sprague-Dawley; Receptors, Cell Surface

Carbon monoxide (CO) is the leading cause of death by poisoning all over the world and may result in neuropathologic changes and cognitive and neurologic sequelae, yet little is known regarding its outcomes. The present study aimed to evaluate the neuroprotective effects of N-butylphthalide (NBP) against brain damage after acute CO poisoning. The animal model of CO poisoning was established by exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min. RT-PCR was used to assess the expressions of apoptosis-associated genes Bcl-2 mRNA and Bax mRNA. Mitochondrial membrane potential (MMP) was detected by fluorescent probe JC-1. Immunohistochemistry stain and Western blot assay were used to evaluate the expression levels of Kelch-like ECH-associated protein 1 (Keapl), nuclear factor erythroid 2-related factor 2 (Nrf-2) and. quinone oxidoreductase 1(NQO-1). CO poisoning could increase the levels of Bcl-2 mRNA and Bax mRNA expressions, and obviously decrease the MMP of cells. NBP treatment could maintain the high MMP, significantly up-regulate Bcl-2 mRNA and down-regulate Bax mRNA expression, and the ratio of Bcl-2 mRNA/Bax mRNA expressions was higher than that in the CO poisoning group (P<0.05). CO poisoning could start oxidative stress response. The expressions of Keap1, Nrf-2 and NQO-1 proteins significantly increased at 1, 3 and 7 day after NBP administration as compared with the CO poisoning group (P<0.01). These findings suggest that N-butylphthalide may protect mitochondrial function, balance the expressions of anti-apoptosis genes and pro-apoptosis genes, be in part associated with activation of Keap1-Nrf-2/antioxidant response element (ARE) signaling pathway, and play a neuroprotective role in brain damage after acute CO poisoning.

Topics: Animals; Apoptosis; Benzofurans; Brain; Carbon Monoxide Poisoning; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; Membrane Potential, Mitochondrial; NF-E2-Related Factor 2; Rats; Signal Transduction

As a wider variety of synthetic materials is used in buildings, the potential for poisoning from inhalation of products of combustion is increasing greatly. Research during the past few years has shown that the burning of plastics (insulation, furniture, carpeting, electric wiring covering, decorative items) results in the formation of large amounts of highly toxic chemicals. Clinicians treating victims of fires should be aware of the toxicological ramifications of combustion, including delayed pathophysiological sequellae. A case report and a review of some current hypotheses of fire-induced toxicity illustrate the current state of knowledge, as well as some uncertainties and controversies in fire toxicology.

Topics: Adult; Benzofurans; Bridged Bicyclo Compounds; Burns, Inhalation; Carbon Monoxide Poisoning; Cyanides; Female; Fires; Free Radicals; Gas Poisoning; Humans; Hydrochloric Acid