BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for severa...BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.展开更多
BACKGROUND Lower respiratory tract viral infections are a major cause of mortality in children under five years old,leading to hundreds of thousands of fatalities annually.The highest risk is observed in infants under...BACKGROUND Lower respiratory tract viral infections are a major cause of mortality in children under five years old,leading to hundreds of thousands of fatalities annually.The highest risk is observed in infants under one year old,underscoring the critical need for safe and effective antiviral protocols.CASE SUMMARY A 9-month-old infant suffered from severe bronchiolitis as manifested by high fever(39°C),decreased appetite,tachypnea,wheezing,and oxygen desaturation(SpO284%on room air)and was effectively managed at home using Kelleni’s protocol,which includes age-adjusted dose of nitazoxanide(60 mg twice daily),ibuprofen and azithromycin,complemented by selective antihistaminic,antitussive and mucolytic immunomodulatory treatment.The fever resolved,wheezing became more prominent but without respiratory distress,and oxygen saturation gradually increased to 92%by day 10.Nitazoxanide exerts broad antiviral and immunomodulatory effects by enhancing host interferon responses and inhibiting viral replication,potentially attenuating airway inflammation and accelerating resolution of bronchiolitis.The nitazoxanide dose(60 mg twice daily for five days)was carefully adjusted based on the developmental expression and activity of the uridine diphosphate-glucuronosyltransferase 1A1 enzyme,responsible for its metabolism,ensuring safe age-appropriate administration.The infant’s clinical status steadily improved,and by day 14 the infant achieved full recovery with normalization of oxygen saturation(96%on room air).No adverse events occurred,and follow-up at day 28 confirmed sustained recovery.CONCLUSION To the best of my knowledge,this report presents,for the first time globally,a potential of nitazoxanide within Kelleni’s protocol to early manage infants younger than one year suffering from severe lower respiratory tract viral infection at home.Selective antitussive treatment,using agents such as low dose benproperine,was employed to mitigate troublesome cough and improve patient comfort without compromising respiratory function.Additionally,alpha amylase was used to facilitate pulmonary secretion clearance.The protocol aims to reduce morbidity and mortality from viral lower respiratory tract infections in this vulnerable population.展开更多
Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognize...Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.展开更多
Three sensitive,selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ),a new anti-protozoal drug,in presence of its degradation products.Method A utilizes the fir...Three sensitive,selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ),a new anti-protozoal drug,in presence of its degradation products.Method A utilizes the first derivative of ratio spectra spectrophotometry by measurement of the amplitude at 364.4 nm using one of the degradation products as a divisor.Method B is a chemometric-assisted spectrophotometry,where principal component regression (PCR) and partial least squares (PLS) were applied.These two approaches were successfully applied to quantify NTZ in presence of degradation products using the information included in the absorption spectra in the range 260-360 nm.Method C is based on the separation of NTZ from its degradation products followed by densitometric measurement of the bands at 254 nm.The separation was carried out on silica gel 60F 254,using chloroform-methanol-ammonia solution-glacial acetic acid (95:5:1:1 by volume,pH=5.80) as a developing system.These methods are suitable as stability-indicating methods for the determination of NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations.Statistical analysis of the results has been carried out revealing high accuracy and good precision.展开更多
Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as sui...Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR genes.The amplicons were directly sequenced to determine gene mutations.Results:The various amino acid substitutions(F:20%,Haplotype diversity:0.891,Tajima's D:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,however,no point mutations was found in symptomatic isolates.Conclusions:Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity.This leads to decrease in metronidazole drug delivery into the cells.Mutations in these isolates may lead to their resistance to metronidazole.No to low synonymous mutations of Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.展开更多
The present study reports voltammetric reduction of nitazoxanide in Britton-Robinson （B-R） buffer by cyclic and square-wave voltammetry at glassy carbon electrode. A versatile fully validated voltammetric method for...The present study reports voltammetric reduction of nitazoxanide in Britton-Robinson （B-R） buffer by cyclic and square-wave voltammetry at glassy carbon electrode. A versatile fully validated voltammetric method for quantitative determination of nitazoxanide in pharmaceutical formulation has been proposed. A squrewave peak current was linear over the nitazoxanide concentration in the range of 20-140 ~tg/mL. The limit of detection （LOD） and limit of quantification （LOQ） was calculated to be 5.23 la~/mL and 17.45 la~/mL, respectively.展开更多
The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus,lipid metabolism disorders,atherosclerosis and inhibit inflammation.Since the pathogenesis of heart fail...The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus,lipid metabolism disorders,atherosclerosis and inhibit inflammation.Since the pathogenesis of heart failure with preserved ejection(HFpEF)is multifactorial and closely associated with the aforementioned diseases,we aim to study the effect of nitazoxanide on high-fat diet(HFD)plus L-NAME(Nω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice.We found that oral nitazoxanide improved cardiac hypertrophy,cardiac fibrosis,cardiac diastolic dysfunction,increased blood pressure,impaired exercise tolerance,impaired glucose handling,serum lipid disorders,hepatic steatosis,increased weight of white adipose tissues and kidney fibrosis in HFD+L-NAME-treated mice.In the established HFD+L-NAME-induced HFpEF and metabolic syndrome mouse model,therapeutic treatment with nitazoxanide rescued HFD+L-NAME-induced pathological phenotypes as mentioned above.The in vitro experiments revealed that tizoxanide,the active metabolite of nitazoxanide,increased the basal mitochondria metabolism of cardiomyocytes,inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts,and relaxed phenylephrine-and U46619-induced constriction of rat mesenteric arteries,indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo.The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.展开更多
Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprot...Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile.We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in Hep G2 cells.Gavage administration of nitazoxanide inhibited high-fat diet(HFD)-induced increases of liver weight,blood and liver lipids,and ameliorated HFD-induced renal lipid accumulation in hamsters.Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers.In the hamsters with pre-existing hyperlipidemia and hepatic steatosis,nitazoxanide also showed therapeutic effect.Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet(WD)-induced hepatic steatosis in Apoe-/-mice.The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.展开更多
The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous st...The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.展开更多
Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s ...Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s disease(AD).In order to further improve the efficacy and discover new chemical entities,a series of NTZ-based derivatives were designed,synthesized,and evaluated as autophagy activator against AD.All compounds were screened by the inhibition of phosphorylation of p70S6K,which was the direct substrate of mammalian target of rapamycin(mTOR)and its phosphorylation level could reflect the mTOR-dependent autophagy level.Among these analogs,compound 22 exhibited excellent potency in promotingβ-amyloid(Aβ)clearance,inhibiting tau phosphorylation,as well as stimulating autophagy both in vitro and in vivo.What’s more,22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice.These results demonstrated that 22 was a potential candidate for the treatment of AD.展开更多
This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute resp...This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron EG.5.1,its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt in 2024.These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever,persistent severe cough,change of voice,loss of taste and smell,epigastric pain,nausea,vomiting,diarrhea,generalized malaise and marked bone aches in adults including the high-risk groups.It’s suggested that the ongoing SARS-CoV-2 evolution is continuing to mostly affect the high-risk groups of patients,to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts.We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients,at least until the currently encountered surge of infections subsides.展开更多
BACKGROUND Fasciola hepatica(F.hepatica)(liver fluke)is a parasitic trematode that infects humans through the consumption of contaminated aquatic plants harboring the infective stage of the parasite.Despite being a ne...BACKGROUND Fasciola hepatica(F.hepatica)(liver fluke)is a parasitic trematode that infects humans through the consumption of contaminated aquatic plants harboring the infective stage of the parasite.Despite being a neglected tropical disease,a World Health Organi-zation report estimates that it affects approximately 2.4 million people worldwide,with high endemicity in regions characterized by poor sanitation and limited access to clean water.Clinical manifestations range from asymptomatic infection to severe complications such as liver abscess and multiorgan involvement.CASE SUMMARY We report 4 cases with varied and unusual presentations.Case 1:A 41-year-old woman with an initial presumptive clinical diagnosis of liver malignancy.Case 2:A 34-year-old woman who presented with urticaria and eosinophilia,initially suspected to be vasculitis.Case 3:A 67-year-old man who presented with dyspeptic symptoms,easy fatigability,headache,and fever.Case 4:A 60-year-old patient who presented with an eosinophilic liver abscess after prolonged antibiotic treatment failure.CONCLUSION Hepatic fascioliasis is frequently misdiagnosed due to its non-specific symptoms and limited diagnostic tools,especially in resource-limited settings.It is crucial to enhance awareness among healthcare professionals regarding its recognition and appropriate management.This case report aims to contribute to the growing body of literature on F.hepatica infection to facilitate timely diagnosis and empiric treatment with triclabendazole or nitazoxanide,as these are effective and reduce unnecessary interventions.展开更多
Diarrhea is a common complication in solid organ transplant(SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually caus...Diarrhea is a common complication in solid organ transplant(SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.展开更多
文摘BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.
文摘BACKGROUND Lower respiratory tract viral infections are a major cause of mortality in children under five years old,leading to hundreds of thousands of fatalities annually.The highest risk is observed in infants under one year old,underscoring the critical need for safe and effective antiviral protocols.CASE SUMMARY A 9-month-old infant suffered from severe bronchiolitis as manifested by high fever(39°C),decreased appetite,tachypnea,wheezing,and oxygen desaturation(SpO284%on room air)and was effectively managed at home using Kelleni’s protocol,which includes age-adjusted dose of nitazoxanide(60 mg twice daily),ibuprofen and azithromycin,complemented by selective antihistaminic,antitussive and mucolytic immunomodulatory treatment.The fever resolved,wheezing became more prominent but without respiratory distress,and oxygen saturation gradually increased to 92%by day 10.Nitazoxanide exerts broad antiviral and immunomodulatory effects by enhancing host interferon responses and inhibiting viral replication,potentially attenuating airway inflammation and accelerating resolution of bronchiolitis.The nitazoxanide dose(60 mg twice daily for five days)was carefully adjusted based on the developmental expression and activity of the uridine diphosphate-glucuronosyltransferase 1A1 enzyme,responsible for its metabolism,ensuring safe age-appropriate administration.The infant’s clinical status steadily improved,and by day 14 the infant achieved full recovery with normalization of oxygen saturation(96%on room air).No adverse events occurred,and follow-up at day 28 confirmed sustained recovery.CONCLUSION To the best of my knowledge,this report presents,for the first time globally,a potential of nitazoxanide within Kelleni’s protocol to early manage infants younger than one year suffering from severe lower respiratory tract viral infection at home.Selective antitussive treatment,using agents such as low dose benproperine,was employed to mitigate troublesome cough and improve patient comfort without compromising respiratory function.Additionally,alpha amylase was used to facilitate pulmonary secretion clearance.The protocol aims to reduce morbidity and mortality from viral lower respiratory tract infections in this vulnerable population.
文摘Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.
文摘Three sensitive,selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ),a new anti-protozoal drug,in presence of its degradation products.Method A utilizes the first derivative of ratio spectra spectrophotometry by measurement of the amplitude at 364.4 nm using one of the degradation products as a divisor.Method B is a chemometric-assisted spectrophotometry,where principal component regression (PCR) and partial least squares (PLS) were applied.These two approaches were successfully applied to quantify NTZ in presence of degradation products using the information included in the absorption spectra in the range 260-360 nm.Method C is based on the separation of NTZ from its degradation products followed by densitometric measurement of the bands at 254 nm.The separation was carried out on silica gel 60F 254,using chloroform-methanol-ammonia solution-glacial acetic acid (95:5:1:1 by volume,pH=5.80) as a developing system.These methods are suitable as stability-indicating methods for the determination of NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations.Statistical analysis of the results has been carried out revealing high accuracy and good precision.
基金financially supported by Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iranthe master’s thesis of the first author(Thesis No.93/2-4/12)
文摘Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR genes.The amplicons were directly sequenced to determine gene mutations.Results:The various amino acid substitutions(F:20%,Haplotype diversity:0.891,Tajima's D:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,however,no point mutations was found in symptomatic isolates.Conclusions:Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity.This leads to decrease in metronidazole drug delivery into the cells.Mutations in these isolates may lead to their resistance to metronidazole.No to low synonymous mutations of Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.
文摘The present study reports voltammetric reduction of nitazoxanide in Britton-Robinson （B-R） buffer by cyclic and square-wave voltammetry at glassy carbon electrode. A versatile fully validated voltammetric method for quantitative determination of nitazoxanide in pharmaceutical formulation has been proposed. A squrewave peak current was linear over the nitazoxanide concentration in the range of 20-140 ~tg/mL. The limit of detection （LOD） and limit of quantification （LOQ） was calculated to be 5.23 la~/mL and 17.45 la~/mL, respectively.
基金supported by the National Natural Science Foundation of China(Nos.82373864 and 82170472).
文摘The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus,lipid metabolism disorders,atherosclerosis and inhibit inflammation.Since the pathogenesis of heart failure with preserved ejection(HFpEF)is multifactorial and closely associated with the aforementioned diseases,we aim to study the effect of nitazoxanide on high-fat diet(HFD)plus L-NAME(Nω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice.We found that oral nitazoxanide improved cardiac hypertrophy,cardiac fibrosis,cardiac diastolic dysfunction,increased blood pressure,impaired exercise tolerance,impaired glucose handling,serum lipid disorders,hepatic steatosis,increased weight of white adipose tissues and kidney fibrosis in HFD+L-NAME-treated mice.In the established HFD+L-NAME-induced HFpEF and metabolic syndrome mouse model,therapeutic treatment with nitazoxanide rescued HFD+L-NAME-induced pathological phenotypes as mentioned above.The in vitro experiments revealed that tizoxanide,the active metabolite of nitazoxanide,increased the basal mitochondria metabolism of cardiomyocytes,inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts,and relaxed phenylephrine-and U46619-induced constriction of rat mesenteric arteries,indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo.The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.
基金supported by the National Natural Science Foundation of China(Nos.81773725 and 91739102)。
文摘Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile.We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in Hep G2 cells.Gavage administration of nitazoxanide inhibited high-fat diet(HFD)-induced increases of liver weight,blood and liver lipids,and ameliorated HFD-induced renal lipid accumulation in hamsters.Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers.In the hamsters with pre-existing hyperlipidemia and hepatic steatosis,nitazoxanide also showed therapeutic effect.Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet(WD)-induced hepatic steatosis in Apoe-/-mice.The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.
基金supported by the National Natural Science Foundation of China(Nos.82373864 and 82170472).
文摘The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.
基金provided by the National Sciences and Technology Major Project of China,(2018ZX09711002-003-010)the National Natural Science Foundation of China,(81872747,21672064)+5 种基金the 111 Project(B07023,China)the Chinese Postdoctoral Science Foundation(2018M641946)the Shanghai Sailing Program(19YF1412600,China)the Shanghai Morning Light Program(18CG33,China)the National Special Fund for State Key Laboratory of Bioreactor Engineering(2060204,China)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_1600,China).
文摘Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s disease(AD).In order to further improve the efficacy and discover new chemical entities,a series of NTZ-based derivatives were designed,synthesized,and evaluated as autophagy activator against AD.All compounds were screened by the inhibition of phosphorylation of p70S6K,which was the direct substrate of mammalian target of rapamycin(mTOR)and its phosphorylation level could reflect the mTOR-dependent autophagy level.Among these analogs,compound 22 exhibited excellent potency in promotingβ-amyloid(Aβ)clearance,inhibiting tau phosphorylation,as well as stimulating autophagy both in vitro and in vivo.What’s more,22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice.These results demonstrated that 22 was a potential candidate for the treatment of AD.
文摘This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron EG.5.1,its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt in 2024.These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever,persistent severe cough,change of voice,loss of taste and smell,epigastric pain,nausea,vomiting,diarrhea,generalized malaise and marked bone aches in adults including the high-risk groups.It’s suggested that the ongoing SARS-CoV-2 evolution is continuing to mostly affect the high-risk groups of patients,to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts.We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients,at least until the currently encountered surge of infections subsides.
文摘BACKGROUND Fasciola hepatica(F.hepatica)(liver fluke)is a parasitic trematode that infects humans through the consumption of contaminated aquatic plants harboring the infective stage of the parasite.Despite being a neglected tropical disease,a World Health Organi-zation report estimates that it affects approximately 2.4 million people worldwide,with high endemicity in regions characterized by poor sanitation and limited access to clean water.Clinical manifestations range from asymptomatic infection to severe complications such as liver abscess and multiorgan involvement.CASE SUMMARY We report 4 cases with varied and unusual presentations.Case 1:A 41-year-old woman with an initial presumptive clinical diagnosis of liver malignancy.Case 2:A 34-year-old woman who presented with urticaria and eosinophilia,initially suspected to be vasculitis.Case 3:A 67-year-old man who presented with dyspeptic symptoms,easy fatigability,headache,and fever.Case 4:A 60-year-old patient who presented with an eosinophilic liver abscess after prolonged antibiotic treatment failure.CONCLUSION Hepatic fascioliasis is frequently misdiagnosed due to its non-specific symptoms and limited diagnostic tools,especially in resource-limited settings.It is crucial to enhance awareness among healthcare professionals regarding its recognition and appropriate management.This case report aims to contribute to the growing body of literature on F.hepatica infection to facilitate timely diagnosis and empiric treatment with triclabendazole or nitazoxanide,as these are effective and reduce unnecessary interventions.
文摘Diarrhea is a common complication in solid organ transplant(SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.
