Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer ...Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.展开更多
The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to ch...The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.展开更多
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants o...Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with 展开更多
AIM: To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. METHODS: Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular m...AIM: To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. METHODS: Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular muscle of proximal colon; LMDC, longitudinal muscle of distal colon; CMDC, circular muscle of distal colon.) was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees C), bubbled continuously with 950 mL.L(-1) O(2) and 50 mL.L(-1) CO(2). The mean contractile amplitude (A), the resting tension (T), and the contractile frequency (F) were simultaneously recorded on recorders. RESULTS: Areca dose dependently increased the mean contractile amplitude, the resting tension of proximal and distal colonic smooth muscle strips in rats (P【0.05). It also partly increased the contractile frequency of colonic smooth muscle strips in rats (P【0.05). The effects were partly inhibited by atropine (the resting tension of LMPC decreased from 0.44 +/- 0.12 to 0.17 +/- 0.03; the resting tension of LMDC decreased from 0.71 +/- 0.14 to 0.03 +/- 0.01; the mean contractile amplitude of LMPC increased from -45.8 +/- 7.2 to -30.5 +/- 2.9; the motility index of CMDC decreased from 86.6 +/- 17.3 to 32.8 +/- 9.3; P【0.05 vs areca), but the effects were not inhibited by hexamethonium (P】0.05). CONCLUSION: Areca stimulated the motility of isolated colonic smooth muscle strips in rats. The stimulation of areca might be relevant with M receptor partly.展开更多
The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents ...The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.展开更多
AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the ...AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.展开更多
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonala...Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.展开更多
AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to p...AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to pharmacy students who collected data on demographics,SUP medications,dose,route,duration and associated risk factors.The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines.Institutional review board approval was obtained from each hospital center.RESULTS:A total of 1004 patients were included.67% of the patients who received prophylaxis did not have an indication for SUP.The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications.Overall,the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample.This misuse was mainly observed in non-teaching hospitals.CONCLUSION:This study highlighted the need,in Lebanese hospitals,to establish clinical practice guidelines for the use of SUP;mainly in non-critical care settings.展开更多
基金The German Research Foundation,No.DFG Ta434/5-1the Interdisciplinary Center for Clinical Research(IZKF)Aachen
文摘Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.
基金This work was supported by the National Basic Research Program(973 Program)(No.2011CB504704)the Ministry of Health of China(2014ZX10004-001,2013ZX10004601).
文摘The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.
文摘Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with
基金the Natural Scientific Foundation of Shandong Province,No.Y2001C06
文摘AIM: To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. METHODS: Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular muscle of proximal colon; LMDC, longitudinal muscle of distal colon; CMDC, circular muscle of distal colon.) was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees C), bubbled continuously with 950 mL.L(-1) O(2) and 50 mL.L(-1) CO(2). The mean contractile amplitude (A), the resting tension (T), and the contractile frequency (F) were simultaneously recorded on recorders. RESULTS: Areca dose dependently increased the mean contractile amplitude, the resting tension of proximal and distal colonic smooth muscle strips in rats (P【0.05). It also partly increased the contractile frequency of colonic smooth muscle strips in rats (P【0.05). The effects were partly inhibited by atropine (the resting tension of LMPC decreased from 0.44 +/- 0.12 to 0.17 +/- 0.03; the resting tension of LMDC decreased from 0.71 +/- 0.14 to 0.03 +/- 0.01; the mean contractile amplitude of LMPC increased from -45.8 +/- 7.2 to -30.5 +/- 2.9; the motility index of CMDC decreased from 86.6 +/- 17.3 to 32.8 +/- 9.3; P【0.05 vs areca), but the effects were not inhibited by hexamethonium (P】0.05). CONCLUSION: Areca stimulated the motility of isolated colonic smooth muscle strips in rats. The stimulation of areca might be relevant with M receptor partly.
文摘The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.
基金Supported by A National Research Foundation of Korea Grant funded by the Korean Government, No. 2010-0004429
文摘AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.
文摘Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.
文摘AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to pharmacy students who collected data on demographics,SUP medications,dose,route,duration and associated risk factors.The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines.Institutional review board approval was obtained from each hospital center.RESULTS:A total of 1004 patients were included.67% of the patients who received prophylaxis did not have an indication for SUP.The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications.Overall,the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample.This misuse was mainly observed in non-teaching hospitals.CONCLUSION:This study highlighted the need,in Lebanese hospitals,to establish clinical practice guidelines for the use of SUP;mainly in non-critical care settings.
