BACKGROUND Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant i...BACKGROUND Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant is time-pressured and often undertaken by psychiatrists without transplant experience.Assessors may identify absolute psychiatric contraindications(APCIs)precluding transplant in otherwise medically suitable patients.It is unknown how often this occurs.The combination of high but unknown mortality,time pressure,and relative inexperience is likely to provoke anxiety in assessors.This study hypothesised that the proportion of POD patients assessed for OLT who die because psychiatric contraindications preclude transplant would be small but not negligible.AIM To determine the proportion of patients with paracetamol-induced AHF,for whom psychiatric contraindications preclude transplantation,and the consequent mortality.METHODS This is an 18-year single-centre retrospective cohort study based in a national liver transplant centre.524 participants were identified from a departmental database and included if they had AHF from suspected POD and received a psychiatric assessment for OLT.For those who died before discharge,records were reviewed for medical and psychiatric contraindications to transplant,alongside age,sex,and primary psychiatric diagnosis.We calculated the proportion of patients assessed for whom APCIs precluded transplant,resulting in death.RESULTS Among 524 patients undergoing psychiatric assessment for OLT,there were 102 in-episode deaths(19.5%).APCIs were identified in 46 patients who were otherwise medically suitable for transplant and went on to die.This statistic represents 8.8%of the number of persons evaluated and 45%of the number of deaths.Within this subgroup,27(59%)were female,with a mean age of 44.6 years(ranging from 19-72 years).The most common primary psychiatric diagnosis was alcohol dependence syndrome,which accounted for 67%(n=31).CONCLUSION 8.8%of medically suitable patients with AHF following POD died with APCIs to transplant.This indicates a need for ongoing assessor training and support,and(inter)national comparisons of practice.展开更多
In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is invo...In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is involved in 56% of acute liver diseases, whereas 0.4% of paracetamol overdose cases result in fatal-ity. In this study, the effects of Moringa oleifera on paracetamol toxicity in the liver were explored. It has been demonstrated that Moringa oleifera is highly nu-tritious, contains bioactive molecules, and is therapeutically beneficial. Many studies have shown that Moringa oleifera leaves possess a wide range of biologi-cal properties, including antioxidant, tissue protection, analgesic, antihyperten-sive, and immunomodulatory activities. This study highlights the protective role of Moringa oleifera on handling possible paracetamol hepatotoxicity in male rats. .展开更多
The pharmaceutical industry is facing challenges due to various factors such as supply chain disruptions,changing consumer behavior,and regulatory changes.Accurate demand forecasting is essential to ensure an adequate...The pharmaceutical industry is facing challenges due to various factors such as supply chain disruptions,changing consumer behavior,and regulatory changes.Accurate demand forecasting is essential to ensure an adequate supply of drugs.The goal of this work is to forecast paracetamol product demand.For this purpose,we propose a hybrid forecasting model combining two effective forecasting techniques:SARIMA(Seasonal AutoRegressive Integrated Moving Average)and ANFIS(Adaptive Neuro-Fuzzy Inference System).This proposal consists of nonlinear components of time series by ANFIS and adjusting the result by the mean of the residuals of the SARIMA to improve the accuracy and performance of ANFIS predictions.Before the prediction phase,we preprocess our data and detect the anomalies in our dataset with Locally Selective Combination in Parallel Outlier Ensembles(LSCP).Then,by treating these anomalies as missing values,they are imputed using the combination of fuzzy-possibilistic c-means(FCM)with support vector regression(SVR)and a genetic algorithm(GA).Finally,we evaluate the performance of the model and some known models based on MAPE.We choose the hybrid model SARIMA-ANFIS that provides the most accurate and reliable forecasting.展开更多
Cetyl-chitosan, prepared by reacting chitosan with chlorocetane under alkaline condition, is soluble and spontaneously forms nanoparticles about 100 nm in diameter. Infrared spectra (IR) revealed that there was a subs...Cetyl-chitosan, prepared by reacting chitosan with chlorocetane under alkaline condition, is soluble and spontaneously forms nanoparticles about 100 nm in diameter. Infrared spectra (IR) revealed that there was a substitution reaction mainly on the amine groups of chitosan (CS). By using paracetamol (PCTM) as a model drug, the balanced release concentration of PCTM in phosphate buffer solution (pH=7.4) can be decreased with the increase of degree of substitution alkyl and can be reduced effectively even under a lower PCTM loading.展开更多
Objective:To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea(C.gigantea)against paracetamol induced liver damage in rats.Methods:The hepatoprotective activity for plant extract...Objective:To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea(C.gigantea)against paracetamol induced liver damage in rats.Methods:The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats.Wislar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days.The normal control group was given 1%Na.CMC 1mL/kg bw,p.o.Paracetamol at dose of 1g/kg bw,p.o.was given as toxic dose for inducing hepatoloxicity.Silymarin(50mg/kg.p.o.) was given as reference standard.Two doses of C. gigantea extract i.e.,100 mg/kg.p.o.and 200 mg/kg,p.o.were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase(SGOT),serum glutamic pyruvic transaminase(SGPT),alkaline phosphatase(ALP),total bilirubin(TB)and total protein(TP)in different groups.Results:The paracetamol intoxication lead to histological and biochemical deteriorations.The treatment with methanolic leaf extract of C.gigantea reduced the elevated levels of SCOT,SGPT,ALP,TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C.gigantea.Conclusions:The methanolic extract of leaves of C.gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.展开更多
Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 an...Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 and silymarin were used as standard drugs and 2%gum acacia as a control(vehicle).Alteration in the levels of biochemical markers of hepatic damage like AST,ALT,ALP and lipid peroxides were tested,and phytochemical tests were also performed.Results:Paracetamol(2 g/kg) increased the serum levels of alanine aminotransfer (ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and the lipid peroxides. Treatment of Liv 52,silymarin and ethanolic extract of Terminalia paniculata(200 mg/kg) altered levels of biochemical marker and showed significant hepatoprotective activity.Ethanolic extract revealed the presence of phenolic compound and flavanoids.Our findings suggested that ethanolic bark extract of Terminalia paniculata possessed hepatoprotective activity in a dose dependent manner.Conclusions:Terminalia paniculata possesses hepatoprotective activity.It could be an effective and promising preventive agent against PCT induced hepatotoxicity.展开更多
Drug induced liver injury(DILI)is a common cause of acute liver injury.Paracetamol,also known as acetaminophen,is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeuti...Drug induced liver injury(DILI)is a common cause of acute liver injury.Paracetamol,also known as acetaminophen,is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels.Hepatotoxicity from paracetamol overdose,whether intentional or nonintentional,is the most common cause of DILI in the United States and remains a global issue.Given the increased prevalence of combination medications in the form of pain relievers and antihistamines,paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity,as evidenced by its contribution to over half of all acute liver failure cases in the United States.This is especially concerning given that,when co-ingested with other medications,the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy.This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.展开更多
A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method...A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity, linearity, accuracy, precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products. The technique encompasses the separation of the analytes with a reverse phase C18 column under isocrafic conditions and UV detection at 272 nm and 243 nm, respectively, for theophylline and paraeetamol. The lower limit of quantification for both drugs was determined as 0.2 μg/mL and the between-batch accuracy was 99.7%. This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design, development and production of milk-based pediatric dosage forms.展开更多
A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy ...A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.展开更多
Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-proce...Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.展开更多
Aim: To evaluate the antireproductive effect of paracetamol in male rats. Methods: Male rats were orally adminis-tered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour ...Aim: To evaluate the antireproductive effect of paracetamol in male rats. Methods: Male rats were orally adminis-tered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertilitywere evaluated using receptive females. Results: At 2 h after treratment, sexual behaviour was not inhibited but onday 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and% ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance(intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implan-tation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductiveeffect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia,impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa.Conclusion: Long-term use of high doses of paracetamol may be detrimental to male reproductive competence.( Asian J Andro12000 Dec; 2: 247-255 )展开更多
This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol...This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol(PCM). The newly formed surface was characterized by scanning electron microscopy(SEM), electrochemical impedance spectroscopy(EIS) and cyclic voltammetry(CV). The results showed greater conductivity and a higher surface area for the composite than those of the carbon paste alone. Moreover, the anodic peak currents for PCM increased from 1.6 to 3.6 m A with CPE and NdOXSWCNT/CPE, indicating an increase of nearly 51.0% for the anodic peak current. On the other hand, the anodic peak potentials shifted from 0.67 to 0.57 V. The detection limits were 0.05 mmol/L with NdOXSWCNT/CPE and 0.50 mmol/L with SWCNT/CPE. The relative standard deviations(RSDs) were 1.5%(n=7). The accuracy and interference of the methods were evaluated with a urine chemistry control spiked with known quantities of PCM, uric acid, dopamine, ascorbic acid, caffeine, acetylsalicylic acid,tartrazine, sunset yellow, allure red, rutin, morin and metal ions. Finally, the novelty and usefulness of the composite were evaluated to quantify PCM in pharmaceutical dosage forms such as tablets, powders and syrups for children.展开更多
Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg...Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+ 200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.展开更多
As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neurotransmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,bu...As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neurotransmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO_(2)-based electrochemical sensor,N-doped carbon@-TiO_(2) double-shelled hollow sphere(HeC/N@TiO_(2))is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO_(2) hollow spheres(H eTiO_(2))or N-doped carbon hollow spheres(HeC/N)are also prepared by the same method.HeC/N@TiO_(2) has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 mmol/L for PA,40.0 nmol/L and 0.3e50 mmol/L for DA,respectively,which are better than those of carbon-based sensors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reliability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of HeC/N@TiO_(2) is attributed to the multifunctional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO_(2).展开更多
BACKGROUND:Numerous drugs have been proposed to alleviate pain in patients with biliary colic,especially opioids,but still there is a tendency to use less narcotics because of their side effects and the unwillingness ...BACKGROUND:Numerous drugs have been proposed to alleviate pain in patients with biliary colic,especially opioids,but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients.The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic.METHODS:A randomized double-blind controlled trial was performed in 98 patients with biliary colic,recruited from two emergency departments from August 2012 to August 2013.Eleven patients were excluded and the remaining were randomized into two groups:group A received 0.05mg/kg morphine+1 000 mg paracetamol in 100 m L normal saline and group B received 0.1 mg/kg morphine+normal saline(100 m L)as placebo.Pain scores were recorded using visual analogue scale(VAS)at baseline and 15 and 30 minutes after drug administration.Adverse effects and the need for rescue medication(0.75 g/kg intravenous fentanyl)were also reported within 60 minutes of drug administration.RESULTS:Before the infusion,the mean±SD VAS scores were 8.73±1.57 in group A and8.53±1.99 in group B.At 15 minutes after drug administration,the mean±SD VAS scores were2.16±1.90 in group A vs.2.51±1.86 in group B;mean difference was–0.35,and 95%CI–1.15 to 0.45(P=0.38).At 30 minutes the mean±SD VAS scores were 1.66±1.59 in group A vs.2.14±1.79 in group B;mean difference was–0.48,and 95%CI–1.20 to 0.24(P=0.19).The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference.CONCLUSION:Paracetamol combined with low-dose morphine may be effective for pain management in patients with biliary colic.展开更多
Nanosized Ba_(1-x)Bi_(x)Fe_(1-x)Cu_(x)O_(3)(12–50 nm)with x values of 0,0.01,0.05,and 0.1 system was prepared using the Pechini method.Structural,morphological,surface and optical characterizations were performed for...Nanosized Ba_(1-x)Bi_(x)Fe_(1-x)Cu_(x)O_(3)(12–50 nm)with x values of 0,0.01,0.05,and 0.1 system was prepared using the Pechini method.Structural,morphological,surface and optical characterizations were performed for the prepared samples.Cubic phase was the predominant phase for the undoped BaFeO_(3)and Bi and Cu co-doped BaFeO_(3)samples.Minor phases of monoclinic Ba_(2)Fe_(2)O_(5),orthorhombic BaFe_(2)O_(4)and orthorhombic BaCO_(3)were identified for all the prepared samples.Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)sample has the lowest band gap(2.43 e V).98.1%paracetamol removal was achieved with 0.75 g/L of Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)at pH9 after 120 min.The paracetamol degradation follows the pseudo first-order kinetics.HO·is the main oxidative species responsible for the paracetamol degradation.Gas chromatography–mass spectrometry(GC–MS)analysis was performed at the end of the photocatalytic degradation experiment under optimum operating condition using Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)to explain the reaction mechanism and identify the intermediate by-products which is confirmed by ultraviolet/visible(UV/Vis)spectroscopy study at different reaction times.展开更多
Objective: To demonstrate the in-vivo hepatoprotective effect of the ethanolic extracts of Citrullus colocynthis (Linn.) against paracetamol induced hepatotoxicity in albino rats. Animal Model: Swiss Albino rats of ei...Objective: To demonstrate the in-vivo hepatoprotective effect of the ethanolic extracts of Citrullus colocynthis (Linn.) against paracetamol induced hepatotoxicity in albino rats. Animal Model: Swiss Albino rats of either sex were used, divided into six groups with six in each group. Group 1-Normal control: The animals were maintained under normal control, which were given distilled water only. Group 2-Induction of hepatotoxicity: The animals received paracetamol 500 mg/kg b.w. (p.o) every 72 h for 10 Days. Groups 3 to 5: Animals received ethanolic extract of Citrullus colocynthis L. at 50, 100 & 200 mg/kg bw/day for 7 days (p.o). Group 6: The animals were treated with Silymarin (100 mg/kg p.o) which served as standard. Groups 3 to 6 were intoxicated with paracetamol (500 mg/kg bw) 1 h before the administration of extract or Silymarin for 10 days. Histopathological findings, different hepatic biochemical parameters viz. AST, ALT, ALP, Total bilirubin, Total cholesterol, Triglycerides, & the body weight before & after treatment were evaluated to investigate the hepatoprotective activity. Results: Paracetamol induced a significant rise in AST, ALT, ALP, Total Bilirubin, Total Cholesterol, Triglycerides. Administration of 200 mg/kg bw of ethanolic extract of Citrullus colocynthis L. effectively reduced these pathological damages caused by paracetamol intoxication. In addition to serum parameters treatment of 200 mg/kg bw of ethanolic extract of Citrulus colocynthis L. also promotes the body weight in albino rats as shown in Figure 6 respectively. Histopathological changes of the liver samples were compared with the normal control as shown in Figures 2-5 respectively. Conclusion: From our results we may infer that the mode of action of 90% ethanolic extract of Citrullus colocynthis L. (200 mg/kg bw) in affording the in-vivo hepatoprotective activity against paracetamol may be due to the cell membrane stabilization, hepatic cell regeneration & normalizing the serum parameters.展开更多
Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as...Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.展开更多
Background and Objectives: Propofol remains the most common drug for induction of general anaesthesia, although it causes considerable pain on injection. None of the commonly used methods completely attenuate this dis...Background and Objectives: Propofol remains the most common drug for induction of general anaesthesia, although it causes considerable pain on injection. None of the commonly used methods completely attenuate this discomfort. We aimed to investigate the effect of i.v. paracetamol pretreatment on the propofol injection pain. Materials and Methods: A prospective randomized double-blind study was conducted on 180 patients, ASA I or II status, scheduled to undergo elective surgery. They were randomly assigned to one of the three groups of 60 each. Groups I, II, III were pretreated with 40 mg of lidocaine in saline, 100 mg of paracetamol and 10 ml of saline, respectively. All patients had an 18-gauge catheter inserted into a superficial radial vein. After 2 min of venous occlusion, one-fourth of the total propofol dose was injected into the vein over a period of 20 seconds. During the injection of both pretreatment solution and propofol, a blinded researcher assessed the patient’s pain level using a four-point verbal rating scale (VRS) (none = 0, mild = 1, moderate = 2, and severe = 3). X2 test and Kruskal-Wallis tests were used for the statistical analysis. For all analyses, differences were considered to be significant at P < 0.05. Results: The three groups were comparable in respect to patient’s characteristics. The incidence of pain on injection of propofol in placebo, i.v. paracetamol and lidocaine groups were 85%, 36%, 21% respectively (p < 0.05). Intensity and severity of propofol induced pain were comparable between paracetamol and lidocaine groups. Conclusion: Pretreatment using i.v. paracetamol was found to be effective in reducing propofol injection-induced pain.展开更多
文摘BACKGROUND Paracetamol overdose(POD)is the most common cause of acute hepatic failure(AHF)in the United Kingdom.Without urgent orthotopic liver transplant(OLT),mortality is high.Psychiatric assessment for transplant is time-pressured and often undertaken by psychiatrists without transplant experience.Assessors may identify absolute psychiatric contraindications(APCIs)precluding transplant in otherwise medically suitable patients.It is unknown how often this occurs.The combination of high but unknown mortality,time pressure,and relative inexperience is likely to provoke anxiety in assessors.This study hypothesised that the proportion of POD patients assessed for OLT who die because psychiatric contraindications preclude transplant would be small but not negligible.AIM To determine the proportion of patients with paracetamol-induced AHF,for whom psychiatric contraindications preclude transplantation,and the consequent mortality.METHODS This is an 18-year single-centre retrospective cohort study based in a national liver transplant centre.524 participants were identified from a departmental database and included if they had AHF from suspected POD and received a psychiatric assessment for OLT.For those who died before discharge,records were reviewed for medical and psychiatric contraindications to transplant,alongside age,sex,and primary psychiatric diagnosis.We calculated the proportion of patients assessed for whom APCIs precluded transplant,resulting in death.RESULTS Among 524 patients undergoing psychiatric assessment for OLT,there were 102 in-episode deaths(19.5%).APCIs were identified in 46 patients who were otherwise medically suitable for transplant and went on to die.This statistic represents 8.8%of the number of persons evaluated and 45%of the number of deaths.Within this subgroup,27(59%)were female,with a mean age of 44.6 years(ranging from 19-72 years).The most common primary psychiatric diagnosis was alcohol dependence syndrome,which accounted for 67%(n=31).CONCLUSION 8.8%of medically suitable patients with AHF following POD died with APCIs to transplant.This indicates a need for ongoing assessor training and support,and(inter)national comparisons of practice.
文摘In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is involved in 56% of acute liver diseases, whereas 0.4% of paracetamol overdose cases result in fatal-ity. In this study, the effects of Moringa oleifera on paracetamol toxicity in the liver were explored. It has been demonstrated that Moringa oleifera is highly nu-tritious, contains bioactive molecules, and is therapeutically beneficial. Many studies have shown that Moringa oleifera leaves possess a wide range of biologi-cal properties, including antioxidant, tissue protection, analgesic, antihyperten-sive, and immunomodulatory activities. This study highlights the protective role of Moringa oleifera on handling possible paracetamol hepatotoxicity in male rats. .
文摘The pharmaceutical industry is facing challenges due to various factors such as supply chain disruptions,changing consumer behavior,and regulatory changes.Accurate demand forecasting is essential to ensure an adequate supply of drugs.The goal of this work is to forecast paracetamol product demand.For this purpose,we propose a hybrid forecasting model combining two effective forecasting techniques:SARIMA(Seasonal AutoRegressive Integrated Moving Average)and ANFIS(Adaptive Neuro-Fuzzy Inference System).This proposal consists of nonlinear components of time series by ANFIS and adjusting the result by the mean of the residuals of the SARIMA to improve the accuracy and performance of ANFIS predictions.Before the prediction phase,we preprocess our data and detect the anomalies in our dataset with Locally Selective Combination in Parallel Outlier Ensembles(LSCP).Then,by treating these anomalies as missing values,they are imputed using the combination of fuzzy-possibilistic c-means(FCM)with support vector regression(SVR)and a genetic algorithm(GA).Finally,we evaluate the performance of the model and some known models based on MAPE.We choose the hybrid model SARIMA-ANFIS that provides the most accurate and reliable forecasting.
文摘Cetyl-chitosan, prepared by reacting chitosan with chlorocetane under alkaline condition, is soluble and spontaneously forms nanoparticles about 100 nm in diameter. Infrared spectra (IR) revealed that there was a substitution reaction mainly on the amine groups of chitosan (CS). By using paracetamol (PCTM) as a model drug, the balanced release concentration of PCTM in phosphate buffer solution (pH=7.4) can be decreased with the increase of degree of substitution alkyl and can be reduced effectively even under a lower PCTM loading.
基金Supported by University Grants Commission.(No.Fdb/Pharmacy/C6102/2008-2010/5162)
文摘Objective:To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea(C.gigantea)against paracetamol induced liver damage in rats.Methods:The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats.Wislar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days.The normal control group was given 1%Na.CMC 1mL/kg bw,p.o.Paracetamol at dose of 1g/kg bw,p.o.was given as toxic dose for inducing hepatoloxicity.Silymarin(50mg/kg.p.o.) was given as reference standard.Two doses of C. gigantea extract i.e.,100 mg/kg.p.o.and 200 mg/kg,p.o.were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase(SGOT),serum glutamic pyruvic transaminase(SGPT),alkaline phosphatase(ALP),total bilirubin(TB)and total protein(TP)in different groups.Results:The paracetamol intoxication lead to histological and biochemical deteriorations.The treatment with methanolic leaf extract of C.gigantea reduced the elevated levels of SCOT,SGPT,ALP,TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C.gigantea.Conclusions:The methanolic extract of leaves of C.gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.
文摘Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 and silymarin were used as standard drugs and 2%gum acacia as a control(vehicle).Alteration in the levels of biochemical markers of hepatic damage like AST,ALT,ALP and lipid peroxides were tested,and phytochemical tests were also performed.Results:Paracetamol(2 g/kg) increased the serum levels of alanine aminotransfer (ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and the lipid peroxides. Treatment of Liv 52,silymarin and ethanolic extract of Terminalia paniculata(200 mg/kg) altered levels of biochemical marker and showed significant hepatoprotective activity.Ethanolic extract revealed the presence of phenolic compound and flavanoids.Our findings suggested that ethanolic bark extract of Terminalia paniculata possessed hepatoprotective activity in a dose dependent manner.Conclusions:Terminalia paniculata possesses hepatoprotective activity.It could be an effective and promising preventive agent against PCT induced hepatotoxicity.
文摘Drug induced liver injury(DILI)is a common cause of acute liver injury.Paracetamol,also known as acetaminophen,is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels.Hepatotoxicity from paracetamol overdose,whether intentional or nonintentional,is the most common cause of DILI in the United States and remains a global issue.Given the increased prevalence of combination medications in the form of pain relievers and antihistamines,paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity,as evidenced by its contribution to over half of all acute liver failure cases in the United States.This is especially concerning given that,when co-ingested with other medications,the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy.This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.
基金the financial support provided by Fundacao para a Ciência e a Tecnologia,Portugal(PTDC/DTP-FTO/1057/2012)
文摘A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity, linearity, accuracy, precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products. The technique encompasses the separation of the analytes with a reverse phase C18 column under isocrafic conditions and UV detection at 272 nm and 243 nm, respectively, for theophylline and paraeetamol. The lower limit of quantification for both drugs was determined as 0.2 μg/mL and the between-batch accuracy was 99.7%. This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design, development and production of milk-based pediatric dosage forms.
基金The authors would like to thank Dr.T.Sivakumar,Principal,Nandha College of Pharmacy and Research Institute,Erode,TN,India for necessary permission to carry out the study and Dr.S.Sengottuvelu,Head,Department of Pharmacology,and Mrs.V.Lalitha,Department of Pharmacology,Nandha College of Pharmacy and Research Institute for their support and suggestions.
文摘A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.
文摘Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.
文摘Aim: To evaluate the antireproductive effect of paracetamol in male rats. Methods: Male rats were orally adminis-tered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertilitywere evaluated using receptive females. Results: At 2 h after treratment, sexual behaviour was not inhibited but onday 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and% ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance(intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implan-tation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductiveeffect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia,impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa.Conclusion: Long-term use of high doses of paracetamol may be detrimental to male reproductive competence.( Asian J Andro12000 Dec; 2: 247-255 )
基金the Universidad de los Andes for financial support from the Interfaculty project and the Faculty of Sciencesthe financial support of the Universidad de Ibagué (project 18-541-INT)COLCIENCIAS (project 130774559056)
文摘This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol(PCM). The newly formed surface was characterized by scanning electron microscopy(SEM), electrochemical impedance spectroscopy(EIS) and cyclic voltammetry(CV). The results showed greater conductivity and a higher surface area for the composite than those of the carbon paste alone. Moreover, the anodic peak currents for PCM increased from 1.6 to 3.6 m A with CPE and NdOXSWCNT/CPE, indicating an increase of nearly 51.0% for the anodic peak current. On the other hand, the anodic peak potentials shifted from 0.67 to 0.57 V. The detection limits were 0.05 mmol/L with NdOXSWCNT/CPE and 0.50 mmol/L with SWCNT/CPE. The relative standard deviations(RSDs) were 1.5%(n=7). The accuracy and interference of the methods were evaluated with a urine chemistry control spiked with known quantities of PCM, uric acid, dopamine, ascorbic acid, caffeine, acetylsalicylic acid,tartrazine, sunset yellow, allure red, rutin, morin and metal ions. Finally, the novelty and usefulness of the composite were evaluated to quantify PCM in pharmaceutical dosage forms such as tablets, powders and syrups for children.
文摘Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+ 200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.
基金supported by the National Natural Science Foundation of China(Grant Nos.:22074058 and 21675077)the Project of Industry-University-Research Cooperation of Fujian Province(Grant No.:2019Y4010)the Education-Science Research Project for Young and Middle-aged Teachers of Fujian(Grant No.:JAT200317).
文摘As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neurotransmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO_(2)-based electrochemical sensor,N-doped carbon@-TiO_(2) double-shelled hollow sphere(HeC/N@TiO_(2))is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO_(2) hollow spheres(H eTiO_(2))or N-doped carbon hollow spheres(HeC/N)are also prepared by the same method.HeC/N@TiO_(2) has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 mmol/L for PA,40.0 nmol/L and 0.3e50 mmol/L for DA,respectively,which are better than those of carbon-based sensors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reliability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of HeC/N@TiO_(2) is attributed to the multifunctional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO_(2).
文摘BACKGROUND:Numerous drugs have been proposed to alleviate pain in patients with biliary colic,especially opioids,but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients.The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic.METHODS:A randomized double-blind controlled trial was performed in 98 patients with biliary colic,recruited from two emergency departments from August 2012 to August 2013.Eleven patients were excluded and the remaining were randomized into two groups:group A received 0.05mg/kg morphine+1 000 mg paracetamol in 100 m L normal saline and group B received 0.1 mg/kg morphine+normal saline(100 m L)as placebo.Pain scores were recorded using visual analogue scale(VAS)at baseline and 15 and 30 minutes after drug administration.Adverse effects and the need for rescue medication(0.75 g/kg intravenous fentanyl)were also reported within 60 minutes of drug administration.RESULTS:Before the infusion,the mean±SD VAS scores were 8.73±1.57 in group A and8.53±1.99 in group B.At 15 minutes after drug administration,the mean±SD VAS scores were2.16±1.90 in group A vs.2.51±1.86 in group B;mean difference was–0.35,and 95%CI–1.15 to 0.45(P=0.38).At 30 minutes the mean±SD VAS scores were 1.66±1.59 in group A vs.2.14±1.79 in group B;mean difference was–0.48,and 95%CI–1.20 to 0.24(P=0.19).The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference.CONCLUSION:Paracetamol combined with low-dose morphine may be effective for pain management in patients with biliary colic.
文摘Nanosized Ba_(1-x)Bi_(x)Fe_(1-x)Cu_(x)O_(3)(12–50 nm)with x values of 0,0.01,0.05,and 0.1 system was prepared using the Pechini method.Structural,morphological,surface and optical characterizations were performed for the prepared samples.Cubic phase was the predominant phase for the undoped BaFeO_(3)and Bi and Cu co-doped BaFeO_(3)samples.Minor phases of monoclinic Ba_(2)Fe_(2)O_(5),orthorhombic BaFe_(2)O_(4)and orthorhombic BaCO_(3)were identified for all the prepared samples.Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)sample has the lowest band gap(2.43 e V).98.1%paracetamol removal was achieved with 0.75 g/L of Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)at pH9 after 120 min.The paracetamol degradation follows the pseudo first-order kinetics.HO·is the main oxidative species responsible for the paracetamol degradation.Gas chromatography–mass spectrometry(GC–MS)analysis was performed at the end of the photocatalytic degradation experiment under optimum operating condition using Ba_(0.95)Bi_(0.05)Fe_(0.95)Cu_(0.05)O_(3)to explain the reaction mechanism and identify the intermediate by-products which is confirmed by ultraviolet/visible(UV/Vis)spectroscopy study at different reaction times.
文摘Objective: To demonstrate the in-vivo hepatoprotective effect of the ethanolic extracts of Citrullus colocynthis (Linn.) against paracetamol induced hepatotoxicity in albino rats. Animal Model: Swiss Albino rats of either sex were used, divided into six groups with six in each group. Group 1-Normal control: The animals were maintained under normal control, which were given distilled water only. Group 2-Induction of hepatotoxicity: The animals received paracetamol 500 mg/kg b.w. (p.o) every 72 h for 10 Days. Groups 3 to 5: Animals received ethanolic extract of Citrullus colocynthis L. at 50, 100 & 200 mg/kg bw/day for 7 days (p.o). Group 6: The animals were treated with Silymarin (100 mg/kg p.o) which served as standard. Groups 3 to 6 were intoxicated with paracetamol (500 mg/kg bw) 1 h before the administration of extract or Silymarin for 10 days. Histopathological findings, different hepatic biochemical parameters viz. AST, ALT, ALP, Total bilirubin, Total cholesterol, Triglycerides, & the body weight before & after treatment were evaluated to investigate the hepatoprotective activity. Results: Paracetamol induced a significant rise in AST, ALT, ALP, Total Bilirubin, Total Cholesterol, Triglycerides. Administration of 200 mg/kg bw of ethanolic extract of Citrullus colocynthis L. effectively reduced these pathological damages caused by paracetamol intoxication. In addition to serum parameters treatment of 200 mg/kg bw of ethanolic extract of Citrulus colocynthis L. also promotes the body weight in albino rats as shown in Figure 6 respectively. Histopathological changes of the liver samples were compared with the normal control as shown in Figures 2-5 respectively. Conclusion: From our results we may infer that the mode of action of 90% ethanolic extract of Citrullus colocynthis L. (200 mg/kg bw) in affording the in-vivo hepatoprotective activity against paracetamol may be due to the cell membrane stabilization, hepatic cell regeneration & normalizing the serum parameters.
文摘Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.
文摘Background and Objectives: Propofol remains the most common drug for induction of general anaesthesia, although it causes considerable pain on injection. None of the commonly used methods completely attenuate this discomfort. We aimed to investigate the effect of i.v. paracetamol pretreatment on the propofol injection pain. Materials and Methods: A prospective randomized double-blind study was conducted on 180 patients, ASA I or II status, scheduled to undergo elective surgery. They were randomly assigned to one of the three groups of 60 each. Groups I, II, III were pretreated with 40 mg of lidocaine in saline, 100 mg of paracetamol and 10 ml of saline, respectively. All patients had an 18-gauge catheter inserted into a superficial radial vein. After 2 min of venous occlusion, one-fourth of the total propofol dose was injected into the vein over a period of 20 seconds. During the injection of both pretreatment solution and propofol, a blinded researcher assessed the patient’s pain level using a four-point verbal rating scale (VRS) (none = 0, mild = 1, moderate = 2, and severe = 3). X2 test and Kruskal-Wallis tests were used for the statistical analysis. For all analyses, differences were considered to be significant at P < 0.05. Results: The three groups were comparable in respect to patient’s characteristics. The incidence of pain on injection of propofol in placebo, i.v. paracetamol and lidocaine groups were 85%, 36%, 21% respectively (p < 0.05). Intensity and severity of propofol induced pain were comparable between paracetamol and lidocaine groups. Conclusion: Pretreatment using i.v. paracetamol was found to be effective in reducing propofol injection-induced pain.
