Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacolog...Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.展开更多
Background: Termination of pregnancy (TOP) in Zambia is guided by the Termination of Pregnancy (TOP) Act of 1972 and as amended in 1994 of the laws of Zambia. However, despite provision of Comprehensive abortion care ...Background: Termination of pregnancy (TOP) in Zambia is guided by the Termination of Pregnancy (TOP) Act of 1972 and as amended in 1994 of the laws of Zambia. However, despite provision of Comprehensive abortion care services with the liberal law, statistics at Kanyama First Level Hospital in relation to unsafe illegal abortions are alarming. This study sought to understand the Awareness on the TOP Act of the laws of Zambia among women of reproductive age 15 - 49 years at Kanyama First Level Hospital in Lusaka District. Purpose of the Study: To assess awareness on the TOP Act among women of reproductive age at Kanyama First Level Hospital in Lusaka, Zambia. Methodology: A convergent parallel mixed method design was conducted using both survey and in-depth interviews among women of reproductive age at Kanyama First Level Hospital in Lusaka District. The study surveyed 370 randomly sampled women aged 15 to 49 years old while the in-depth interviews included eight women purposively sampled from the survey population. Survey data was analyzed using descriptive and inferential statistics while qualitative data thematic analysis was used. Results: The study found that 37% of the participants were aware of the TOP Act while 63.8% viewed legalization of abortion for any reason as wrong. The study results also showed that widowed women were 8 times more likely to be aware of the TOP Act compared to single women (AOR: 8.262;95% CI: 1.105, 61.778). Women in business were significantly more likely to be aware of the TOP Act compared to those who reported having no occupation. (AOR: 2.61;95% CI: 1.246, 5.499). Limited access to information, the social stigma attached to abortion, health care providers’ attitudes, cultural norms, values and religious beliefs, restrictive legal requirements, and absence of a supportive network were some of the barriers affecting awareness and utilization of available safe abortion care services. Conclusions: The research findings concluded that a significant lack of awareness among women of reproductive age regarding the Termination of Pregnancy (TOP) Act. The majority of respondents held the view that abortion should only be legalized for medical reasons. Furthermore, there was a notable gap in knowledge concerning the penal code’s provisions on abortion.展开更多
The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological ...The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).展开更多
Objective: The aim of the current study was to assess the impact of operative interventions for misplaced device among women who opted for PPIIUCD and the evaluation of reasons for PPIUCD removal within the follow up ...Objective: The aim of the current study was to assess the impact of operative interventions for misplaced device among women who opted for PPIIUCD and the evaluation of reasons for PPIUCD removal within the follow up period of two years. Design: A descriptive exploratory study was conducted over three months among fourteen PPIUCD acceptors at a tertiary care health facility in Delhi, India. Face-to-face & telephonic in-depth interviews were conducted with a selected sample of PPIUCD acceptors who had later opted for its removal. Results: Participants (n = 14) aged 24 – 40 exhibited generally positive attitudes towards PPIUCDs indicating an indicate an understanding of the importance of PPIUCD in preventing unintended pregnancies. Menstrual disturbance and misplaced IUCD were major reasons for removal. despite their own experience necessitating the removal of IUCD, positive experience by other family members (mothers in law) in this study helped to keep the confidence on the contraceptive. Themes included (a) general experience of PPIUCD use (b) Health Facility accessed for removal of IUCD (c) Would she recommend it to others? (d) preferred contraceptive after removal of IUCD. Conclusion: Misplaced IUCD, missing thread, menstrual irregularities, and pain are all associated with PPIUCD and are important reasons for dissatisfaction. Appropriate, timely and supportive individualized care that address knowledge gaps, societal perceptions, and healthcare system challenges would certainly help in reducing dissatisfaction due to PPIUCD and thereby the removal rates.展开更多
Objective:To investigate and compare the hepatoprotective effects of crude ethanolic and aqueous extracts of Phyllanthus acidus(L.) Skeels(P.acidus) leaves on acetaminophen(APAP) and thioacetamide(TAA) induced...Objective:To investigate and compare the hepatoprotective effects of crude ethanolic and aqueous extracts of Phyllanthus acidus(L.) Skeels(P.acidus) leaves on acetaminophen(APAP) and thioacetamide(TAA) induced liver toxicity in wistar rats.Silymarin was the reference hepatoprotective agent.Methods:In two different sets of experiments,the P.acidus extracts (200 and 400 mg/kg,body weight) and silymarin(100 mg/kg,body weight) were given orally for 7 days and a single dose of APAP(2 g/kg,per oral) or TAA(100 mg/kg,subcutaneous) were given to rats.The level of serum aspartate transaminase(AST),alanine transaminase(ALT),alkaline phosphatase(ALP),total bilirubin and total protein were monitored to assess hepatotoxicity and hepatoprotection.Results:APAP or TAA administration caused severe hepatic damage in rats as evident from significant rise in serum AST,ALT,ALP,total bilirubin and concurrent depletion in total serum protein.The P.acidus extracts and silymarin prevented the toxic effects of APAP or TAA on the above serum parameters indicating the hepatoprotective action.The aqueous extract was found to be more potent than the corresponding ethanolic extract against both toxicants.The phenolic and flavonoid content(175.02±4.35 and 74.68±1.28,respectively) and 2,2-diphenyl-1- picrylhydrazil(DPPH)[IC<sub>50</sub>=(33.2±0.31)μg/mL]scavenging potential was found maximum with aqueous extract as compared to ethanolic extract.Conclusions:The results of present study suggests that the aqueous extract of P.acidus leaves has significant hepatoprotective activity on APAP and TAA induced hepatotoxicity,which might be associate with its high phenolic and flavonoid content and antioxidant properties.展开更多
OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP t...OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.展开更多
Many plant-derived natural products have the potential to be hepatoprotective and therefore can be used to treat acute and chronic liver diseases. The challenge is to identify the most promising compounds and evaluate...Many plant-derived natural products have the potential to be hepatoprotective and therefore can be used to treat acute and chronic liver diseases. The challenge is to identify the most promising compounds and evaluate their protective mechanism. In a recently published article, Wang et al evaluated extracts of the plant Gentiana manshurica Kitagawa (GM) in a model of acetaminophen hepatotoxicity. The authors concluded that GM is hepatoprotective against acetaminopheninduced liver injury due to its antioxidant properties and anti-apoptotic capacity. We would like to discuss the limitations of this experimental approach and question the conclusion based on the data presented in this manuscript and the published literature.展开更多
基金supported by the National Key R&D Program of China(2023YFB3507004)National Natural Science Foundation of China(U21A20148)+5 种基金International Partnership Program of Chinese Academy of Sciences(116134KYSB20210052)Anhui Provincial Natural Science Foundation(2308085QE183,2308085QE181)CASHIPS Director’s Fund(YZJJ2024QN44,YZJJ2023QN43)Heye Health Technology Chong Ming Project(HYCMP2021010)China Post-doctoral Science Foundation(2023M743536)Science Research Fund for Postdoctoral in Anhui Province(2023B669)。
文摘Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.
文摘Background: Termination of pregnancy (TOP) in Zambia is guided by the Termination of Pregnancy (TOP) Act of 1972 and as amended in 1994 of the laws of Zambia. However, despite provision of Comprehensive abortion care services with the liberal law, statistics at Kanyama First Level Hospital in relation to unsafe illegal abortions are alarming. This study sought to understand the Awareness on the TOP Act of the laws of Zambia among women of reproductive age 15 - 49 years at Kanyama First Level Hospital in Lusaka District. Purpose of the Study: To assess awareness on the TOP Act among women of reproductive age at Kanyama First Level Hospital in Lusaka, Zambia. Methodology: A convergent parallel mixed method design was conducted using both survey and in-depth interviews among women of reproductive age at Kanyama First Level Hospital in Lusaka District. The study surveyed 370 randomly sampled women aged 15 to 49 years old while the in-depth interviews included eight women purposively sampled from the survey population. Survey data was analyzed using descriptive and inferential statistics while qualitative data thematic analysis was used. Results: The study found that 37% of the participants were aware of the TOP Act while 63.8% viewed legalization of abortion for any reason as wrong. The study results also showed that widowed women were 8 times more likely to be aware of the TOP Act compared to single women (AOR: 8.262;95% CI: 1.105, 61.778). Women in business were significantly more likely to be aware of the TOP Act compared to those who reported having no occupation. (AOR: 2.61;95% CI: 1.246, 5.499). Limited access to information, the social stigma attached to abortion, health care providers’ attitudes, cultural norms, values and religious beliefs, restrictive legal requirements, and absence of a supportive network were some of the barriers affecting awareness and utilization of available safe abortion care services. Conclusions: The research findings concluded that a significant lack of awareness among women of reproductive age regarding the Termination of Pregnancy (TOP) Act. The majority of respondents held the view that abortion should only be legalized for medical reasons. Furthermore, there was a notable gap in knowledge concerning the penal code’s provisions on abortion.
文摘The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).
文摘Objective: The aim of the current study was to assess the impact of operative interventions for misplaced device among women who opted for PPIIUCD and the evaluation of reasons for PPIUCD removal within the follow up period of two years. Design: A descriptive exploratory study was conducted over three months among fourteen PPIUCD acceptors at a tertiary care health facility in Delhi, India. Face-to-face & telephonic in-depth interviews were conducted with a selected sample of PPIUCD acceptors who had later opted for its removal. Results: Participants (n = 14) aged 24 – 40 exhibited generally positive attitudes towards PPIUCDs indicating an indicate an understanding of the importance of PPIUCD in preventing unintended pregnancies. Menstrual disturbance and misplaced IUCD were major reasons for removal. despite their own experience necessitating the removal of IUCD, positive experience by other family members (mothers in law) in this study helped to keep the confidence on the contraceptive. Themes included (a) general experience of PPIUCD use (b) Health Facility accessed for removal of IUCD (c) Would she recommend it to others? (d) preferred contraceptive after removal of IUCD. Conclusion: Misplaced IUCD, missing thread, menstrual irregularities, and pain are all associated with PPIUCD and are important reasons for dissatisfaction. Appropriate, timely and supportive individualized care that address knowledge gaps, societal perceptions, and healthcare system challenges would certainly help in reducing dissatisfaction due to PPIUCD and thereby the removal rates.
文摘Objective:To investigate and compare the hepatoprotective effects of crude ethanolic and aqueous extracts of Phyllanthus acidus(L.) Skeels(P.acidus) leaves on acetaminophen(APAP) and thioacetamide(TAA) induced liver toxicity in wistar rats.Silymarin was the reference hepatoprotective agent.Methods:In two different sets of experiments,the P.acidus extracts (200 and 400 mg/kg,body weight) and silymarin(100 mg/kg,body weight) were given orally for 7 days and a single dose of APAP(2 g/kg,per oral) or TAA(100 mg/kg,subcutaneous) were given to rats.The level of serum aspartate transaminase(AST),alanine transaminase(ALT),alkaline phosphatase(ALP),total bilirubin and total protein were monitored to assess hepatotoxicity and hepatoprotection.Results:APAP or TAA administration caused severe hepatic damage in rats as evident from significant rise in serum AST,ALT,ALP,total bilirubin and concurrent depletion in total serum protein.The P.acidus extracts and silymarin prevented the toxic effects of APAP or TAA on the above serum parameters indicating the hepatoprotective action.The aqueous extract was found to be more potent than the corresponding ethanolic extract against both toxicants.The phenolic and flavonoid content(175.02±4.35 and 74.68±1.28,respectively) and 2,2-diphenyl-1- picrylhydrazil(DPPH)[IC<sub>50</sub>=(33.2±0.31)μg/mL]scavenging potential was found maximum with aqueous extract as compared to ethanolic extract.Conclusions:The results of present study suggests that the aqueous extract of P.acidus leaves has significant hepatoprotective activity on APAP and TAA induced hepatotoxicity,which might be associate with its high phenolic and flavonoid content and antioxidant properties.
文摘OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.
文摘Many plant-derived natural products have the potential to be hepatoprotective and therefore can be used to treat acute and chronic liver diseases. The challenge is to identify the most promising compounds and evaluate their protective mechanism. In a recently published article, Wang et al evaluated extracts of the plant Gentiana manshurica Kitagawa (GM) in a model of acetaminophen hepatotoxicity. The authors concluded that GM is hepatoprotective against acetaminopheninduced liver injury due to its antioxidant properties and anti-apoptotic capacity. We would like to discuss the limitations of this experimental approach and question the conclusion based on the data presented in this manuscript and the published literature.