Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalizatio...Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.展开更多
Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract of...Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.展开更多
The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolizatio...The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.展开更多
AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer be...AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.展开更多
Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen...Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.展开更多
Chemotherapy-induced toxicity,resulting from inter-individual variability in pharmacokinetics is emerging as a highly active area of investigation.Body composition analysis,primarily concerning the amount of fat mass(...Chemotherapy-induced toxicity,resulting from inter-individual variability in pharmacokinetics is emerging as a highly active area of investigation.Body composition analysis,primarily concerning the amount of fat mass(FM)and lean body mass(LBM),has provided a proof-concept that the inter-individual variability in pharmacokinetics and toxicity profiles may be partially explained by the discrepancies of FM and LBM in patients.Recent research suggests a close relationship among body composition,pharmacokinetics and toxicity of anticancer drugs.Because LBM and FM,significantly influence the exposure to drugs,they are considered as the promising predictors of chemotherapy-induced toxicity and a potential basis for optimizing the dosing of oncology drugs and the outcomes.Our review summarizes the recent studies rendering the aforementioned correlations to highlight that a critical evaluation of body composition has initiated a new era for dose standardization.展开更多
Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different h...Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.展开更多
Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB agg...Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.展开更多
930547 A study on hepatoxicity of thioglycolicacid through percutaneous administration.ZHANG Li(张黎),et al.Faculty Public Heal-ty,Harbin Med Univ,Harbin 150001.Chin J In-dustr Hyg & Occupat Dis 1993;11(2):69—72....930547 A study on hepatoxicity of thioglycolicacid through percutaneous administration.ZHANG Li(张黎),et al.Faculty Public Heal-ty,Harbin Med Univ,Harbin 150001.Chin J In-dustr Hyg & Occupat Dis 1993;11(2):69—72.Thioglycolic acid(TGA)in dosage of 30,100,300mg/kg was administered to rats by singledermal application in acute experiment.And thedosages were 5,50 and 150 mg/kg once a week insubchronic experiment whish lasted for 10weeks.The results showed disturbances of展开更多
AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- ind...AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.展开更多
Drug combination based on synergistic effect is commonly used in clinical practice,especially in the application of traditional medicine.Exploring the combination mechanism could help to better utilize this synergisti...Drug combination based on synergistic effect is commonly used in clinical practice,especially in the application of traditional medicine.Exploring the combination mechanism could help to better utilize this synergistic advantage.However,current research focuses more on the efficacy enhancing of drugs,while ignoring the toxicity reducing effects.Here,we established two drug synergy patterns based on the different situations of drugs and targets,in order to better illuminate the synergistic mechanism of drugs.展开更多
Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the ...Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.展开更多
基金Supported by Italian Ministry of Health(IRCCS Burlo Garofolo),No.RC 7_2014,No.RC 10_2019progetto fondo di ricerca Ateneo,Universitàdi Trieste,No.FRA2018
文摘Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.
基金financially supported by Department of Science&Technology,Government of India,New Delhi(Grant no.GAP-274625)
文摘Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.
文摘The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.
文摘AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.
文摘Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.
文摘Chemotherapy-induced toxicity,resulting from inter-individual variability in pharmacokinetics is emerging as a highly active area of investigation.Body composition analysis,primarily concerning the amount of fat mass(FM)and lean body mass(LBM),has provided a proof-concept that the inter-individual variability in pharmacokinetics and toxicity profiles may be partially explained by the discrepancies of FM and LBM in patients.Recent research suggests a close relationship among body composition,pharmacokinetics and toxicity of anticancer drugs.Because LBM and FM,significantly influence the exposure to drugs,they are considered as the promising predictors of chemotherapy-induced toxicity and a potential basis for optimizing the dosing of oncology drugs and the outcomes.Our review summarizes the recent studies rendering the aforementioned correlations to highlight that a critical evaluation of body composition has initiated a new era for dose standardization.
文摘Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.
基金financially supported by the Offi ce of Research and Standards, Office of Generic Drugs, CDER at the FDA (75F40120C00055)
文摘Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.
文摘930547 A study on hepatoxicity of thioglycolicacid through percutaneous administration.ZHANG Li(张黎),et al.Faculty Public Heal-ty,Harbin Med Univ,Harbin 150001.Chin J In-dustr Hyg & Occupat Dis 1993;11(2):69—72.Thioglycolic acid(TGA)in dosage of 30,100,300mg/kg was administered to rats by singledermal application in acute experiment.And thedosages were 5,50 and 150 mg/kg once a week insubchronic experiment whish lasted for 10weeks.The results showed disturbances of
文摘AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.
基金This work was supported by the National Natural Science Foundation of China(No.82003982,82274313,82204746).
文摘Drug combination based on synergistic effect is commonly used in clinical practice,especially in the application of traditional medicine.Exploring the combination mechanism could help to better utilize this synergistic advantage.However,current research focuses more on the efficacy enhancing of drugs,while ignoring the toxicity reducing effects.Here,we established two drug synergy patterns based on the different situations of drugs and targets,in order to better illuminate the synergistic mechanism of drugs.
文摘Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.