A conventional solid-state process was used to synthesize the double perovskite materials HoRCoMnO_(6)(R=Ho,Gd,Eu,Nd).The structural properties of the compounds were investigated using X-ray powder diffraction(XRD).Th...A conventional solid-state process was used to synthesize the double perovskite materials HoRCoMnO_(6)(R=Ho,Gd,Eu,Nd).The structural properties of the compounds were investigated using X-ray powder diffraction(XRD).The results revealed that Ho_(2)CoMnO_(6) crystallizes in a monoclinic structure with the P2_(1)/n space group.In contrast,the other compounds HoRCoMnO_(6)(R=Gd,Eu,or Nd) exhibit an orthorhombic structure with the Pnma space group.As a result,the average crystallite size also changes as a function of rare-earth element doping.This investigation reveals that the magnetic properties of the compounds studied are significantly dependent on the doping elements.The Curie temperature T_C,for example,increases from 80 to 118℃ with the ionic radii of rare earths increasing.Furthermore,the study of the magnetocaloric effect(MCE) shows that the maximum of the entropy variation(-ΔS_(M)^(max)) increases from 4.97 to 6.06 J/(kg·K) under a magnetic field of 5 T with substitution by rare-earth ions.To examine the efficiency of MCE materials,the relative cooling power(RCP) was evaluated and is found to increase with increment of rare-earth radius till 406.69 J/kg for Nd.The mean entropy variation with tempe rature(TEC) was also studied.Due to their significant magnetocaloric performance,HoRCoMnO_(6)(noted as HRCMO) compounds(with R=Ho,Gd,Eu or Nd) could be good candidates for low-temperature magnetic cooling applications.展开更多
AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the ...AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the heterogenic cancer-derived NCI-N87 cell line were isolated,by stably-transducing it with the human telomerase reverse-transcriptase(h TERT) catalytic subunit gene.The clones were first characterized regarding their cell growth pattern and phenotype.For that we measured the clones' adherence properties,expression of cell-cell junctions' markers(ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance.The gastric properties of the clones,concerning expression of mucins,zymogens and glycan contents,were then evaluated by haematoxylin and eosin staining,Periodic acid Schiff(PAS) and PAS/Alcian Blue-staining,immunocytochemistry and Western blot.In addition,we assessed the usefulness of the h TERT-expressing gastric cell line for H.pylori research,by performing co-culture assays and measuring the IL-8 secretion,by ELISA,upon infection with two H.pylori strains differing in virulence.RESULTS:Compared with the parental cell line,themost promising NCI-hT ERT-derived clones(CL5 and CL6) were composed of cells with homogenous phenotype,presented higher relative telomerase activities,better adhesion properties,ability to be maintained in culture for longer periods after confluency,and were more efficient in PAS-reactive mucins secretion.Both clones were shown to produce high amounts of MUC1,MUC2 and MUC13.NCI-hT ERT-CL5 mucins were shown to be decorated with blood group H type 2(BG-H),Lewis-x(Lex),Ley and Lea and,in a less extent,with BG-A antigens,but the former two antigens were not detected in the NCI-h TERT-CL6.None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans.Entailing good gastric properties,both NCIhT ERT-clones were found to produce pepsinogen-5 and human gastric lipase.The progenitor-like phenotype of NCI-hT ERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5,supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.CONCLUSION:These traits,in addition to resistance to microaerobic conditions and good responsiveness to H.pylori co-culture,in a strain virulence-dependent manner,make the NCI-hT ERT-CL6 a promising model for future in vitro studies.展开更多
Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit(ICU)admissions with high mortality.Systemic steroids are proposed as a valid therapeutic option even though...Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit(ICU)admissions with high mortality.Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial.Heterogeneity of published data regarding study design,population demographics,severity of illness,dosing,type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions.However,it is reasonable to admit that,as it was not found any advantage of corticosteroid therapy in so diverse conditions,such beneficial effects do not exist at all.Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies.Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay.Finally,it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection.Thus its current use in s evere influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.展开更多
Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia...Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.展开更多
Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly...Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly composed of misfolded and aggregatedα-synuclein are the pathological hallmark of PD and other disorders known as synucleinopathies.Molecular studies present evidence that amphetamine upregulatesα-synuclein synthesis in substantia nigra.The increment ofα-synuclein levels promotes its aggregation and amyloid fibril formation,increasing reactive oxygen species(ROS),and consequently dopamine oxidation(Wang and Witt,2014),known to be toxic for dopaminergic neurons involved in motor function and limbicmotor integration.Over the years,these damaged cells lose their functionality and may die precociously,depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD,when a critical number of cells are lost(Garwood et al.,2006).Therefore,the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism,in conjugation to other risk factors that a given individual may hold.Despite the evidence,a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure,and consequently its implication in the PD development(Kish et al.,2017).展开更多
Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.Th...Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.This study aimed at identifying biomarkers to predict response to BCG treatment.Methods:Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3,6,9,and 12.Cytokines tumor necrosis factor(TNF)-α,interleukin(IL)-10,interferon(IFN)-γ,IL-1β,IL-2,IL-4,and IL-6;chemokines CCL2,CCL3,CCL8,CXCL9,and IP-10;and mediators of cytotoxicity CTLA4,Fas-L,Perf,GNLY,NOS2A,and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast(within 24 h)and prolonged changes resulting from treatment.Results:BCG instillation led to fast-increased expression of IL-1β,TNF-α,and IL-10 genes.When compared to relapsing patients,patients with no relapses within one year showed significantly lower expression of IL-1βat 1st week and less IFN-γ,HMOX-1,and GNLY at week 6.HMOX-1 and GNLY were independent predictive biomarkers,and values above the cut-off≥110 and≥13.0‰mRNA,respectively,were considered prejudicial factors.Patients with two HMOX-1 and GNLY factors had highest(66.7%)relapsing risk.Conclusion:Assessing immunomodulators’expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’relapses after BCG treatment.展开更多
Objective:We sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day)via water or in food pellets,and to compare its effects in the paradigms of learned helplessness,locomotion,hedonic sta...Objective:We sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day)via water or in food pellets,and to compare its effects in the paradigms of learned helplessness,locomotion,hedonic state,and anxiety.Methods:Water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice.Next,baseline scores for O-maze,dark/light box,and sucrose tests were measured.Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine.Lastly,all groups were subjected to novel cage,open field,O-maze,dark/light box,sucrose test,and forced swim test to assess the effects of the treatment.Results:In na?ve mice,imipramine delivered via food,induced a reduction of total floating and increased latency in the forced swim test,i.e.,antidepressant-like effects.No other significant effects were found.Dosing with water did not change behavior in the forced swim,sucrose preference test,anxiety,or locomotor paradigms,but increased exploration in the novel cage.Conclusions:Voluntary ingestion is an effective method of chronic dosing with imipramine in na?ve mice.Delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test,with no effects on anxiety,locomotion,or preference behaviors.In contrast,no such effects were observed with treatment via drinking water,suggesting that a higher dose may be required.Our work argues for a broader use of oral delivery using food-treated pellets,in small rodent models of pre-clinical depression.It may substantially improve animal welfare and overcome potential confounds in translational research,which are frequently associated with adverse chronic invasive pharmacotherapies.展开更多
文摘A conventional solid-state process was used to synthesize the double perovskite materials HoRCoMnO_(6)(R=Ho,Gd,Eu,Nd).The structural properties of the compounds were investigated using X-ray powder diffraction(XRD).The results revealed that Ho_(2)CoMnO_(6) crystallizes in a monoclinic structure with the P2_(1)/n space group.In contrast,the other compounds HoRCoMnO_(6)(R=Gd,Eu,or Nd) exhibit an orthorhombic structure with the Pnma space group.As a result,the average crystallite size also changes as a function of rare-earth element doping.This investigation reveals that the magnetic properties of the compounds studied are significantly dependent on the doping elements.The Curie temperature T_C,for example,increases from 80 to 118℃ with the ionic radii of rare earths increasing.Furthermore,the study of the magnetocaloric effect(MCE) shows that the maximum of the entropy variation(-ΔS_(M)^(max)) increases from 4.97 to 6.06 J/(kg·K) under a magnetic field of 5 T with substitution by rare-earth ions.To examine the efficiency of MCE materials,the relative cooling power(RCP) was evaluated and is found to increase with increment of rare-earth radius till 406.69 J/kg for Nd.The mean entropy variation with tempe rature(TEC) was also studied.Due to their significant magnetocaloric performance,HoRCoMnO_(6)(noted as HRCMO) compounds(with R=Ho,Gd,Eu or Nd) could be good candidates for low-temperature magnetic cooling applications.
基金Supported by Grants from the Fundao para a Ciência e a Tecnologia(FCT,Portugal),No.PPCDT/SAL-IMI/57297/2004 and No.PTDC/BIM-MEC/1051/2012The Swedish Cancer foundation+2 种基金The Swedish Research Council,No.K2010-79X-21372-01-3Forska utan djurfrsk,Animal Free ResearchResearch fellowship 2011 from the Sociedade Portuguesa de Gastrenterologia(Portugal)
文摘AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the heterogenic cancer-derived NCI-N87 cell line were isolated,by stably-transducing it with the human telomerase reverse-transcriptase(h TERT) catalytic subunit gene.The clones were first characterized regarding their cell growth pattern and phenotype.For that we measured the clones' adherence properties,expression of cell-cell junctions' markers(ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance.The gastric properties of the clones,concerning expression of mucins,zymogens and glycan contents,were then evaluated by haematoxylin and eosin staining,Periodic acid Schiff(PAS) and PAS/Alcian Blue-staining,immunocytochemistry and Western blot.In addition,we assessed the usefulness of the h TERT-expressing gastric cell line for H.pylori research,by performing co-culture assays and measuring the IL-8 secretion,by ELISA,upon infection with two H.pylori strains differing in virulence.RESULTS:Compared with the parental cell line,themost promising NCI-hT ERT-derived clones(CL5 and CL6) were composed of cells with homogenous phenotype,presented higher relative telomerase activities,better adhesion properties,ability to be maintained in culture for longer periods after confluency,and were more efficient in PAS-reactive mucins secretion.Both clones were shown to produce high amounts of MUC1,MUC2 and MUC13.NCI-hT ERT-CL5 mucins were shown to be decorated with blood group H type 2(BG-H),Lewis-x(Lex),Ley and Lea and,in a less extent,with BG-A antigens,but the former two antigens were not detected in the NCI-h TERT-CL6.None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans.Entailing good gastric properties,both NCIhT ERT-clones were found to produce pepsinogen-5 and human gastric lipase.The progenitor-like phenotype of NCI-hT ERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5,supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.CONCLUSION:These traits,in addition to resistance to microaerobic conditions and good responsiveness to H.pylori co-culture,in a strain virulence-dependent manner,make the NCI-hT ERT-CL6 a promising model for future in vitro studies.
文摘Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit(ICU)admissions with high mortality.Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial.Heterogeneity of published data regarding study design,population demographics,severity of illness,dosing,type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions.However,it is reasonable to admit that,as it was not found any advantage of corticosteroid therapy in so diverse conditions,such beneficial effects do not exist at all.Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies.Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay.Finally,it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection.Thus its current use in s evere influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.
文摘Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.
基金supported by Egas Moniz Cooperativa de Ensino Superior.ST was supported by Fundação para a Ciência e Tecnologia project 02/SAICT/2017/029656 and iNOVA4Health-UIDB/04462/2020a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência,Portugal,through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.
文摘Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly composed of misfolded and aggregatedα-synuclein are the pathological hallmark of PD and other disorders known as synucleinopathies.Molecular studies present evidence that amphetamine upregulatesα-synuclein synthesis in substantia nigra.The increment ofα-synuclein levels promotes its aggregation and amyloid fibril formation,increasing reactive oxygen species(ROS),and consequently dopamine oxidation(Wang and Witt,2014),known to be toxic for dopaminergic neurons involved in motor function and limbicmotor integration.Over the years,these damaged cells lose their functionality and may die precociously,depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD,when a critical number of cells are lost(Garwood et al.,2006).Therefore,the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism,in conjugation to other risk factors that a given individual may hold.Despite the evidence,a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure,and consequently its implication in the PD development(Kish et al.,2017).
基金supported by a grant of Astellas Pharma,obtained after application.
文摘Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.This study aimed at identifying biomarkers to predict response to BCG treatment.Methods:Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3,6,9,and 12.Cytokines tumor necrosis factor(TNF)-α,interleukin(IL)-10,interferon(IFN)-γ,IL-1β,IL-2,IL-4,and IL-6;chemokines CCL2,CCL3,CCL8,CXCL9,and IP-10;and mediators of cytotoxicity CTLA4,Fas-L,Perf,GNLY,NOS2A,and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast(within 24 h)and prolonged changes resulting from treatment.Results:BCG instillation led to fast-increased expression of IL-1β,TNF-α,and IL-10 genes.When compared to relapsing patients,patients with no relapses within one year showed significantly lower expression of IL-1βat 1st week and less IFN-γ,HMOX-1,and GNLY at week 6.HMOX-1 and GNLY were independent predictive biomarkers,and values above the cut-off≥110 and≥13.0‰mRNA,respectively,were considered prejudicial factors.Patients with two HMOX-1 and GNLY factors had highest(66.7%)relapsing risk.Conclusion:Assessing immunomodulators’expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’relapses after BCG treatment.
基金the the Fundacao para a Ciência e Tecnologia(FCT)and Internationale Stichting Alzheimer Onderzoek(ISAO)the Netherlands,grant N 09501 and RFBR 11-04-01411 to TS
文摘Objective:We sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day)via water or in food pellets,and to compare its effects in the paradigms of learned helplessness,locomotion,hedonic state,and anxiety.Methods:Water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice.Next,baseline scores for O-maze,dark/light box,and sucrose tests were measured.Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine.Lastly,all groups were subjected to novel cage,open field,O-maze,dark/light box,sucrose test,and forced swim test to assess the effects of the treatment.Results:In na?ve mice,imipramine delivered via food,induced a reduction of total floating and increased latency in the forced swim test,i.e.,antidepressant-like effects.No other significant effects were found.Dosing with water did not change behavior in the forced swim,sucrose preference test,anxiety,or locomotor paradigms,but increased exploration in the novel cage.Conclusions:Voluntary ingestion is an effective method of chronic dosing with imipramine in na?ve mice.Delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test,with no effects on anxiety,locomotion,or preference behaviors.In contrast,no such effects were observed with treatment via drinking water,suggesting that a higher dose may be required.Our work argues for a broader use of oral delivery using food-treated pellets,in small rodent models of pre-clinical depression.It may substantially improve animal welfare and overcome potential confounds in translational research,which are frequently associated with adverse chronic invasive pharmacotherapies.
