Acetaminophen Treatment Research Articles

The Mechanism and Inflammatory Markers Involved in the Potential Use of N-acetylcysteine in Chronic Pain Management

N-acetylcysteine (NAC) has established use as an antidote for acetaminophen overdose and treatment for pulmonary conditions and nephropathy. It plays a role in regulating oxidative stress and interacting with various cytokines including IL-1β, TNFα, IL-8, IL-6, IL-10, and NF-κB p65. The overexpression of reactive oxygen species (ROS) is believed to contribute to chronic pain states by inducing inflammation and accelerating disease progression, favoring pain persistence in neuropathic and musculoskeletal pain conditions. Through a comprehensive review, we aim to explore the mechanisms and inflammatory pathways through which NAC may manage neuropathic and musculoskeletal pain. Evidence suggests NAC can attenuate neuropathic and musculoskeletal pain through mechanisms such as inhibiting matrix metalloproteinases (MMPs), reducing reactive oxygen species (ROS), and enhancing glutamate transport. Additionally, NAC may synergize with opioids and other pain medications, potentially reducing opioid consumption and enhancing overall pain management. Further research is needed to fully elucidate its therapeutic potential and optimize its use in pain management. As an adjuvant therapy, NAC shows potential for chronic pain management, offering significant benefits for public health.

Adenosine kinase protects against acetaminophen-induced acute liver injury by activating autophagy in hepatocytes

Acute liver injury (ALI) is a common life-threatening condition with a high mortality rate due to liver disease-related death. However, current therapeutic interventions for ALI remain ineffective, and the development of effective novel therapies is urgently needed. Liver samples from patients with drug-induced ALI were collected to detect adenosine kinase (ADK) expression. Male C57BL/6 J mice, hepatocyte-specific ADK knockout (ADKHKO) mice, and their controls (ADKf/f) were exposed to acetaminophen (APAP) and other treatments to investigate the mechanisms of APAP-related ALI. ADK expression was significantly decreased in APAP-injured livers. Hepatocyte-specific ADK deficiency exacerbated APAP-induced ALI, while a gain-of-function approach delivering AAV-ADK, markedly alleviated APAP-induced ALI, as indicated by changes in alanine aminotransferases (ALT) levels, aspartate aminotransferase (AST) levels, neutrophil infiltration and hepatocyte death. This study showed that ADK played a critical role in ALI by activating autophagy through two signaling pathways, the adenosine monophosphate-activated protein kinase (AMPK)-mTOR pathway and the adenosine receptor A1 (ADORA1)-Akt-mTOR pathway. Furthermore, we found that metformin upregulated ADK expression in hepatocytes and protected against APAP-induced ALI. These results demonstrate that ADK is critical in protecting against APAP-induced ALI and that developing therapeutics targeting ADK-adenosine-ADORA1 is a new approach for ALI treatment. Metformin is a potential candidate for preventing ALI by upregulating ADK.Graphical

Simultaneous Oxidation of Trace Organics and Sorption of Trace Metals by Ferrate (Fe(VI))-Coated Sand in Synthetic Wastewater Effluent.

The increased presence of toxic chemicals in aquatic matrices and their associated health effects raise the need for more effective treatment technologies. The application of Fe(VI), an advanced oxidation treatment agent with disinfecting and coagulating capabilities, is limited by Fe(VI) aqueous instability. Our previous study proposed an Fe(VI)-coated sand media to overcome this constraint and demonstrated that Fe(VI)-coated sand was an effective medium for the treatment of phenolic compounds. In this study, we assessed the potential of the media for treatment of acetaminophen (ACM), benzotriazole (BZT), sulfamethoxazole (SMX), copper (Cu), lead (Pb), and zinc (Zn)-common contaminants found in wastewater effluents-in ultrapure and synthetic wastewater effluent. Fe(VI)-coated sand reactivity was influenced by the solution pH and aqueous chemistry. For example, the removal of Pb improved by 39% in the presence of trace organics, indicating that trace metal removal was enhanced by Fe(III) phases formed during Fe(VI) reactions with trace organics. While oxidation of trace organic compounds increased as pH decreased, trace metal sorption was more favorable at higher pH (i.e., pH 8 and 9). The oxidation efficiency of trace organics by the media was the highest for ACM and SMX while BZT degradation was limited due to formation of Cu-BZT complexes. Batch tests in synthetic wastewater effluent revealed that the presence of divalent cations (i.e., Ca2+ and Mg2+) can catalyze Fe(VI) self-decay and promote Fe(III) production and subsequent trace metal removal; however, oxidation of trace organics was hindered in this matrix. This study highlights the potential for Fe(VI)-coated sand application for the treatment of complex matrices more representative of natural and engineered aquatic systems.

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

Prediction of drug-induced liver injury (DILI) potential of drugs is one of the most challenging issues of drug development. Zebrafish larvae provide an in vivo and robust test platform. Due to the ease of handling developing larvae between 2 - 5 days post fertilization (dpf) has been extensively used as a DILI test model. However, the liver is not fully functional at this stage. Here, the importance of larval liver maturation was tested by applying selected known DILI-rank drugs to liver reporter zebrafish between 2-5 dpf and 5-7 dpf. Acetaminophen (most-DILI) treatment caused a significant dose-dependent reduction in liver size only at the early stage. Isoniazid (most-DILI) administration after liver maturation induced hepatomegaly, while it induced liver size reduction between 2-5 dpf. Chlorambucil (less-DILI) treatment induced opposing effects on liver size, in the two stages tested. A non-DILI agent chloramphenicol did not induce any liver size change in either larval stage. Clinical observations were better reproduced when isoniazid and chlorambucil were administered after liver maturation. Our findings show that often-overlooked liver maturity status is a critical parameter for the evaluation of DILI.

Dissecting Acute Drug-Induced Hepatotoxicity and Therapeutic Responses of Steatotic Liver Disease Using Primary Mouse Liver and Blood Cells in a Liver-On-A-Chip Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based liver sinusoid model to mimic MASLD pathomechanisms and investigate the therapeutic effects of drug candidates lanifibranor and resmetirom. Mouse liver primary hepatocytes, hepatic stellate cells, Kupffer cells, and endothelial cells are seeded in a dual-chamber biocompatible liver-on-a-chip (LoC). The LoC is then perfused with circulating immune cells (CICs). Acetaminophen (APAP) and free fatty acids (FFAs) treatment recapitulate acute drug-induced liver injury and MASLD, respectively. As a benchmark for the LoC, multiplex immunofluorescence on livers from APAP-injected and dietary MASLD-induced mice reveals characteristic changes on parenchymal and immune cell populations. APAP exposure induces cell death in the LoC, and increased inflammatory cytokine levels in the circulating perfusate. Under FFA stimulation, lipid accumulation, cellular damage, inflammatory secretome, and fibrogenesis are increased in the LoC, reflecting MASLD. Both injury conditions potentiate CIC migration from the perfusate to the LoC cellular layers. Lanifibranor prevents the onset of inflammation, while resmetirom decreases lipid accumulation in hepatocytes and increases the generation of FFA metabolites in the LoC. This study demonstrates the LoC potential for functional and molecular evaluation of liver disease drug candidates.

Influence of Pre-treatment of Withania somnifera Root Extract and Cow Urine on Hemato-biochemical Parameters in Acetaminophen-induced Toxicity in Swiss Albino Male Mice

Background: The present study was undertaken to investigate protective activity of W. somnifera root extract (W.S.R.E.), cow urine (C.U.) and their combination against acetaminophen (APAP) induced toxicity in male mice. APAP also known as paracetamol, is a well-known drug used for its analgesic and antipyretic effects. However, outside of the therapeutic window, the toxicity may result. W.S. and C.U. are from indigenous sources of plant and animal origins, respectively with several therapeutic activities. Methods: Sixty adult swiss albino male mice were randomly divided into six groups, comprising of ten mice in each group. Group I (control group) received 2% gum acacia suspension for 14 days orally and on day 14, 0.9% NaCl (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents. Group II, III, IV, V and VI received 2% gum acacia, silymarin (@25 mg/kg b.wt.), W.S.R.E. (@100 mg/kg b.wt.), C.U. (@7.8 mL/kg b.wt.) and W.S.R.E. (@100 mg/kg b.wt.) and C.U. (@7.8 mL/kg b.wt.) co-treatment orally for 14 days and on day 14, APAP (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents as mentioned. On 15th day, the animals were sacrificed and samples were collected to study various hematobiochemical and growth related parameters. Result: The treatment of acetaminophen caused significant decrease in haemoglobin, total erythrocyte count whereas increase in total leucocyte and prothrombine time. There were significant (p£0.05) decreases in plasma total protein, albumin and globulin values in group II (APAP), as compared to control (group I). Treatment with W.S. +C.U attenuates these alterations. W.S.R.E., C.U. and their combination pre-treatment mildly restored the changes to normal observed following APAP exposure in mice. However, the results of co-treatment group were more pronounced as compared to individual treatment groups. Thus, it was concluded that treatment with W.S.R.E. and C.U. curtailed the toxic effect of APAP, however, co-administration of both potentiated the protective effect.

Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Clinical and echocardiography predictors of response to first-line acetaminophen treatment in preterm infants with hemodynamically significant patent ductus arteriosus.

To assess clinical and echocardiography predictors of acetaminophen response for the treatment of patent ductus arteriosus (PDA) in preterm neonates. Retrospective cohort study of preterm infants born <30 weeks, with a diagnosis of hemodynamically significant PDA, who received 1st line treatment with intravenous acetaminophen during the first 2 postnatal weeks. Response was defined by PDA closure or improvement in PDA score of >50%. A total of 100 infants were included whose median weight and gestational age at birth were 663 grams and 24.6 weeks respectively. In total, 66 infants were classified as responders and were more likely to have intrauterine growth restriction, exposure to maternal hypertension and chorioamnionitis. Non-response was more common among infants with thrombocytopenia and anemia. Responders were more likely to be IUGR with echocardiography indices of lower preload. Response to 1st line intravenous acetaminophen therapy is comparable to non-steroidal drugs in preterm infants. Relationship of response to acetaminophen to perinatal characteristics requires further characterization.

Association between acetaminophen administration and clinical outcomes in patients with sepsis admitted to the ICU: a retrospective cohort study.

Sepsis, affecting over 30 million people worldwide each year, is a key mortality risk factor in critically ill patients. There are significant regional discrepancies in its impact. Acetaminophen, a common over-the-counter drug, is often administered to control fever in suspected infection cases in intensive care units (ICUs). It is considered generally safe when used at therapeutic levels. Despite its widespread use, there's inconsistent research regarding its efficacy in sepsis management, which creates uncertainties for ICU doctors about its possible advantages or harm. To address this, we undertook a retrospective cohort study utilizing the MIMIC-IV database to examine the correlation between acetaminophen use and clinical outcomes in septic patients admitted to the ICU. We gathered pertinent data on sepsis patients from the MIMIC-IV database. We used propensity score matching (PSM) to pair acetaminophen-treated patients with those who were not treated. We then used Cox Proportional Hazards models to examine the relationships between acetaminophen use and factors such as in-hospital mortality, 30-day mortality, hospital stay duration, and ICU stay length. The data analysis involved 22,633 sepsis patients. Post PSM, a total of 15,843 patients were matched; each patient not receiving acetaminophen treatment was paired with two patients who received it. There was a correlation between acetaminophen and a lower in-hospital mortality rate (HR 0.443; 95% CI 0.371-0.530; p < 0.001) along with 30-day mortality rate (HR 0.497; 95% CI 0.424-0.583; p < 0.001). Additionally, it correlated with a decrease in the duration of hospitalization [8.4 (5.0, 14.8) vs. 9.0 (5.1, 16.0), p < 0.001] and a shorter ICU stay [2.8 (1.5, 6.0) vs. 3.1 (1.7, 6.5); p < 0.05]. The use of acetaminophen may lower short-term mortality in critically ill patients with sepsis. To confirm this correlation, future research should involve multicenter randomized controlled trials.

A single-institution experience of acute toxicities in patients treated with short course hypofractionated radiotherapy in locally advanced rectal cancer.

92 Background: Hypofractionated short course radiation treatment (SCRT) as part of a total neoadjuvant treatment (TNT) approach to treat rectal cancer has increased in popularity since the publication of the RAPIDO trial. However, the literature on SCRT for rectal cancer has not reported significant acute toxicities in the weeks immediately following the completion of treatment. This study examines the acute toxicities in patients treated with hypofractionated radiation therapy as part of their definitive treatment for rectal cancer. Methods: At our institution, we retrospectively analyzed 71 patients with locally advanced rectal cancer treated between 2016-2022 with SCRT (25 Gy in 5 fractions) as part of definitive treatment. Acute toxicity caused by radiation was defined as that occurring from the start of radiation treatment to either 30 days post radiation completion, the start of chemotherapy, or date of surgery, whichever occurred first. Acute neuropathic lumbosacral (LSN) pain was defined as bilateral radiating pain down the lower extremities. Matched patients without reported LSN pain were identified and matched on N stage, location of tumor, and treatment position. Organs at risk were contoured on the CT planning scan and dosimetric analysis was conducted on the patient’s treatment plan. Results: In 71 patients treated with SCRT, we identified diarrhea (n=34, 47.9%), rectal pain (n=15, 21.1%), rectal urgency (n=15, 21.1%) nausea (n=14, 19.7%), and rectal bleeding (n=12, 16.9%) as frequent acute toxicities in the setting of SCRT. For patients with rectal pain, 31.2% required steroids. We also identified an acute toxicity of LSN pain in 10 patients (14.1%). Patients rated this LSN pain between moderate and severe; median time to LSN pain was 2 days (range 1-6 days). For LSN pain, management was conservative for 3 (30%) patients and symptoms self-resolved. The other 7 patients required ibuprofen and acetaminophen treatment; 2 of these patients had persistent symptoms and one was treated with topical hydrocortisone and gabapentin and the other with a burst of methylprednisolone. Dosimetric analysis of the lumbosacral nerve plexus area did not detect a statistically significant difference in dose parameters between symptomatic and asymptomatic patients. Conclusions: We have identified acute toxicities in patients treated with short course hypofractionated radiation, including diarrhea, rectal pain requiring steroid treatment, and previously underappreciated neuropathic lumbosacral pain. Toxicities mainly occurred within one week of treatment and resolved. Further analysis will seek to identify predictive factors of these acute toxicities and to determine whether there is a correlation between these observed acute toxicities and long-term outcomes.

Protective effect of nanocurcumin on acetaminophen-induced hepatic and renal toxicities in pigeons.

In this study, the effects of nanocurcumin on acetaminophen-induced acute hepatorenal toxicity in domestic pigeons (Columba livia) were investigated. Fifteen pigeons were randomly assigned into three groups. Group I was served as a negative control group and received tap water as a placebo. Pigeons in groups II and III were administered acetaminophen at the beginning of the experiment (hr 0). Group III was further treated with nanocurcumin, at 12 hr after acetaminophen administration, being continued every 12 hr for two days. The birds were observed for clinical signs of acute drug toxicity. Blood samples were collected from the pigeons at hr 0, 12, 24 and 48 of the experiment for biochemical analysis of the serum. The results showed that acetaminophen toxicity increased the serum levels of aspartate aminotransferase, alanine aminotransferase, urea and uric acid in the pigeons. Nanocurcumin treatment of acetaminophen intoxicated pigeons attenuated increases in biomarkers of the liver and kidney functions towards control levels. Also, the consumption of nanocurcumin minimized histopathological changes in the liver and kidney. A mortality of 60.00% was seen in the acetaminophen-induced toxicity group; while, none of the birds treated with nanocurcumin died. It can be concluded that nanocurcumin alleviates the acetaminophen-induced acute toxic liver and kidney damages, which can lead to pigeon mortality.

Investigation of the Effects of Resveratrol on Paracetamol Toxicity Established in Hep3B Cells

Aim: We therefore wanted to investigate acetaminophen hepatotoxicity by using Hep3B human hepatoma cells exposed to acetaminophen and resveratrol, used as a protective agent. Specifically, we studied the role of some proinflammatory markers and oxidative damage as possible mechanisms of acetaminophen-associated cytotoxicity.&#x0D; Materials and Method: The Hep3B human hepatoma cell line was used for this study. In vitro studies (GSH, SOD, CAT, AST, ALT, TNF-alpha, IL-6 and cell viability) were performed by using different methods such as Biochemical analyzer, RT-PCR, ELISA and MTT. Acetaminophen and resveratrol were applied to cells in a different time and doses.&#x0D; Results: Only acetaminophen treatment decreased SOD, CAT and GSH levels in Hep3B cells whereas acetaminophen and resveratrol co-treatment increased these enzymes levels. On the other hand, acetaminophen and resveratrol co-treatment (especially 160 µM dose of resveratrol) lead a severe increase in TNF-alpha and IL-6 levels.&#x0D; Conclusion: It is shown that acetaminophen has caused hepatotoxicity but interestingly but resveratrol treatment effects the related parameters mentioned above. Only, acetaminophen administration may cause abnormal decreases and/or increases in antioxidant enzymes and proinflammatory cytokines levels. Additionally, acetaminophen and high dose resveratrol co-treatment triggered the inflammation and oxidative stress. These results showed that resveratrol have a potential to be an effective agent on the treatment and protection of hepatic damage.

Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA. We analyzed acetaminophen metabolites and liver biomarkers in plasma from SMA patients and healthy controls (HC) every hour for six or eight hours on day 1 and day 3 of treatment with therapeutic doses of acetaminophen. Twelve patients with SMA (six adults and six children) and 11 HC participated in the study. Adult patients with SMA had significantly lower clearance of acetaminophen compared to HC (14.1 L/h vs. 21.5 L/h). Formation clearance of acetaminophen metabolites, glucuronide, sulfate, and oxidative metabolites were two-fold lower in the patients compared to HC. The liver transaminases and microRNAs increased nine-fold in one adult SMA patient after two days of treatment. The other patients and HC did not develop abnormal liver biomarkers. In this study, patients with SMA had lower clearance and slower metabolism of acetaminophen, and one patient developed liver involvement. We recommend giving 15 mg/kg/dose to SMA adults (with a maximum of 4000 mg/day) and monitoring standard liver biomarkers 48 h after first-time treatment of acetaminophen.

Selenium Ameliorates Acetaminophen-Induced Oxidative Stress via MAPK and Nrf2 Pathways in Mice.

Overdose of acetaminophen (paracetamol), a widely used non-prescriptive analgesic and antipyretic medication, is one of the main causes of drug-induced acute liver failure around the world. Oxidative stress contributes to this hepatotoxicity. Antioxidants are known to protect the liver from oxidative stress. Selenium, a potent antioxidant, is a commonly used micronutrient. Here, we evaluated the protective effect of selenium on acetaminophen-induced hepatotoxicity. Treating Wistar albino mice with sodium selenite (1mg/kg) before or after inducing hepatotoxicity with acetaminophen (150mg/kg) significantly reduced the levels of liver injury biomarkers such as serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase. In addition, selenium-treated mice showed decreased levels of oxidative stress markers such as protein carbonyls and myeloperoxidase. Acetaminophen treatment stimulated all three mitogen-activated protein kinases (MAPKs) and Keap1 and decreased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 in liver and in isolated mouse peritoneal macrophages, which was reversed by selenium treatment. Our findings suggest that the reactive oxygen species-mediated Nrf2 and MAPK pathways are critical players in acetaminophen-induced hepatotoxicity. These key findings offer an alternative therapeutic target for addressing acetaminophen-induced hepatotoxicity.

Does Liposomal Bupivacaine Injectable Suspension Peripheral Nerve Block Further Aid in Decreasing At-home Narcotic Utilization in Children and Adolescents After Anterior Cruciate Ligament Reconstruction

Background: Opioid misuse and addiction among children and adolescents is an increasingly concerning problem. This study sought to determine whether liposomal bupivacaine injectable suspension admixture administered as a single-shot adductor canal peripheral nerve block (SPNB+BL) would decrease utilization of at-home opioid analgesics after anterior cruciate ligament reconstruction (ACLR) in adolescents compared with single-shot peripheral nerve block with bupivacaine (SPNB+B) alone. Methods: Consecutive ACLR patients with or without meniscal surgery by a single surgeon were enrolled. All received a preoperative single-shot adductor canal peripheral nerve block with either admixture of liposomal bupivacaine injectable suspension with 0.25% bupivacaine (SPNB+BL) or 0.25% bupivacaine alone (SPNB+B). Postoperative pain management included cryotherapy, oral acetaminophen, and ibuprofen. A prescription for 10 doses of hydrocodone/acetaminophen (5/325 mg) was provided in a sealed envelope with instructions to only use in the case of uncontrolled pain. Pain using the visual analog scale; number of consumed narcotics, acetaminophen, ibuprofen, and pain treatment satisfaction for the first 3 postoperative days were recorded. Statistical analysis was performed. Results: Fifty-eight patients were enrolled, the average age was 15±1.5 years (SPNB+B=32 patients, SPNB+BL=26 patients). Forty-seven patients (81%) did not require home opioids postoperatively. A significantly lower proportion of patients in the SPNB+BL group required opioids compared with control patients (7.7% vs. 28.1%, P=0.048). Average opioid use was 2 morphine milligram equivalents (MME), 0.4 pills (range, 0 to 20 MME). There were no differences in the visual analog scale or pain treatment satisfaction scores, other demographics, or other operative data. Inverse probability of treatment weighting analysis that was performed to account for any potential group differences revealed home opioid use between groups is significantly different (P&lt;0.001). Conclusions: Liposomal bupivacaine injectable suspension admixture administered as an adductor canal nerve block in adolescents undergoing ACLR effectively reduces home opioid usage postoperatively compared with bupivacaine alone. Level of Evidence: Level II—prospective comparative study.

Assessment of Anti-Hepatotoxic Effect of Bahuinia tomentosa Linn against Paracetamol induced Hepatocellular Damage In Albino Mice

In today’s modern world the chemical induced hepatotoxicity is one huge threat to human life, even the drugs which have easy accessibility and availability are also produces side effects, when they are used irrationally, so the need for antidote from herbal industry is a common factor. Bauhinia tomentosa Linn belongs to fabaceae, considered as one such potential agent which constitutes wide range of chemical compounds which has therapeutic as well as antidote effect. In this study Bahuinia tomentosa Linn was extracted with ethyl alcohol and the prepared ethanolic extract was evaluated for its hepato protective effect against Acetaminophen induced hepato toxicity in albino mice. The biochemical estimation, histo pathological studies are served as index for the assessment of hepatoprotective activity. Modification in body and liver weight, proteins, levels of biomarkers, antioxidant enzymes along with histopatological variations of extract treated groups were compared with standard hepatoprotective drug silymarin. Marked hepatoprotective activity was noticed in extract treated groups in dose dependent manner. The study results revealed the antihepatato toxic effect of Bauhinia tomentosa Linn and recommended as an excellent natural source of drug in the treatment of acetaminophen induced hepatotoxicity.

Effects of Acetaminophen on Reproductive Activities in Male Golden Hamsters

Acetaminophen [Paracetamol, N-acetyl-para-aminophenol (APAP)] is a common over-the- counter analgesic agent as nonsteroidal anti-inflammatory drugs (NSAIDs). The high doses or the long-term treatment of acetaminophen via usual gavage feeding resulted in damage of testicles that presented recoverable impairment, as well as liver and kidney. The influence of acetaminophen was examined in male golden hamsters treated with acetaminophen- containing diet feeding. They were divided into 5 groups and subjected to this experiment for 4 weeks: animals housed in long photoperiod (LP) as LP control, animals housed in short photoperiod (SP) for 4 weeks as SP control (SP4), and groups of animals treated with low, middle, and high concentrations of acetaminophen (Low, Middle, High groups). Also animals housed in SP for 8 weeks were included (SP8) to contrast testicular activities, if necessary. As results, spermatozoa filled the seminiferous tubules of the testicles of animals in LP control and SP4 groups. The aspects were seen in the animals taken diets of low and middle doses of acetaminophen. The animals who fed high dose of acetaminophen showed large or small testicles. The large testicles displayed all germ cells at the steps of spermatogenesis. The small testicles presented no sperm as the animals housed in SP for 8 weeks. Thus these results indicate that acetaminophen invokes the antigonadal effects and accelerates the regressing process of the testicles in the animals compared to the animals exposed to SP.

Effects of Acetaminophen on Reproductive Activities in Male Golden Hamsters

Acetaminophen [Paracetamol, N-acetyl-para-aminophenol (APAP)] is a common over-the- counter analgesic agent as nonsteroidal anti-inflammatory drugs (NSAIDs). The high doses or the long-term treatment of acetaminophen via usual gavage feeding resulted in damage of testicles that presented recoverable impairment, as well as liver and kidney. The influence of acetaminophen was examined in male golden hamsters treated with acetaminophen- containing diet feeding. They were divided into 5 groups and subjected to this experiment for 4 weeks: animals housed in long photoperiod (LP) as LP control, animals housed in short photoperiod (SP) for 4 weeks as SP control (SP4), and groups of animals treated with low, middle, and high concentrations of acetaminophen (Low, Middle, High groups). Also animals housed in SP for 8 weeks were included (SP8) to contrast testicular activities, if necessary. As results, spermatozoa filled the seminiferous tubules of the testicles of animals in LP control and SP4 groups. The aspects were seen in the animals taken diets of low and middle doses of acetaminophen. The animals who fed high dose of acetaminophen showed large or small testicles. The large testicles displayed all germ cells at the steps of spermatogenesis. The small testicles presented no sperm as the animals housed in SP for 8 weeks. Thus these results indicate that acetaminophen invokes the antigonadal effects and accelerates the regressing process of the testicles in the animals compared to the animals exposed to SP.

Cardiac surgery-associated acute kidney injury in newborns: A meta-analysis

&lt;b&gt;Introduction&lt;/b&gt;: Acute kidney injury is a common complication following pediatric heart surgery, and it has been linked to an increased risk of morbidity and fatality.&lt;br /&gt; &lt;b&gt;Methods&lt;/b&gt;: The PubMed and Medline databases were combed for relevant research until May 2022. The terms [Cardiac surgery] AND [acute renal injury] AND [newborns OR children OR neonates] AND [randomized control studies OR randomized control trials] were used as search criteria. The studies that met the inclusion criteria were considered qualified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.&lt;br /&gt; &lt;b&gt;Results&lt;/b&gt;: A total of 2,941 newborns or children were enrolled in 14 studies, with 931 developing acute renal damage. 2,095 of the enrolled infants and children received steroid, aminophylline, dexmedetomidine, and acetaminophen therapies. In seven studies, the odds ratio for steroids was not significantly different from control. In contrast, two studies comparing aminophylline to a control group found no statistically significant change. Two studies found no significant difference in dexmedetomidine therapy compared to control. Three trials, however, found a significant difference between the acetaminophen treatment and control groups.&lt;br /&gt; &lt;b&gt;Conclusion&lt;/b&gt;: Acetaminophen was linked to a decreased risk of postoperative acute renal injury, while steroids had no benefit and aminophylline treatment could be justified.