[Actual Access and Usage of Antipyretic Analgesics before and after COVID-19 Vaccination: Pharmacist's Roles in Promoting Proper Use of Medicines during the Infodemic].

An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.

Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

Almond fixed oil from Syagrus coronata (Mart.) Becc. has antinociceptive and anti-inflammatory potential, without showing oral toxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Syagrus coronata, a palm tree found in northeastern Brazil, popularly known as licuri, has socioeconomic importance for the production of vegetable oil rich in fatty acids with nutritional and pharmacological effects. Licuri oil is used in traditional medicine to treat inflammation, wound healing, mycosis, back discomfort, eye irritation, and other conditions. AIM OF THE STUDY: The study aimed to evaluate the antinociceptive, anti-inflammatory, and antipyretic effects of treatment with Syagrus coronata fixed oil (ScFO), as well as to determine the safety of use in mice. MATERIALS AND METHODS: Initially, the chemical characterization was performed by gas chromatography-mass spectrometry. Acute single-dose oral toxicity was evaluated in mice at a dose of 2000 mg/kg. Antinociceptive activity was evaluated through abdominal writhing, formalin, and tail dipping tests, and the anti-inflammatory potential was evaluated through the model of acute inflammation of ear edema, peritonitis, and fever at concentrations of 25, 50, and 100 mg/kg from ScFO. RESULTS: In the chemical analysis of ScFO, lauric (43.64%), caprylic (11.7%), and capric (7.2%) acids were detected as major. No mortality or behavioral abnormalities in the mice were evidenced over the 14 days of observation in the acute toxicity test. ScFO treatment decreased abdominal writhing by 27.07, 28.23, and 51.78% at 25, 50, and 100 mg/kg. ScFO demonstrated central and peripheral action in the formalin test, possibly via opioidergic and muscarinic systems. In the tail dipping test, ScFO showed action from the first hour after treatment at all concentrations. ScFO (100 mg/kg) reduced ear edema by 63.76% and leukocyte and neutrophil migration and IL-1ß and TNF-α production in the peritonitis test. CONCLUSION: Mice treated with ScFO had a reduction in fever after 60 min at all concentrations regardless of dose. Therefore, the fixed oil of S. coronata has the potential for the development of new pharmaceutical formulations for the treatment of pain, inflammation, and fever.

The antipyretic effect of the famous classical formula Qingwanzi Pills on a rabbit model and its serum metabolomic study.

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.

Antipyretic and anti-inflammatory effects of inosine, an active component of Kangfuxin.

Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.

A Study on the Antibacterial, Antispasmodic, Antipyretic, and Anti-Inflammatory Activity of ZnO Nanoparticles Using Leaf Extract from Jasminum sambac (L. Aiton).

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution's potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells.

Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model.

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Antipyretic effect of inhaled Tetrastigma hemsleyanum polysaccharide on substance and energy metabolism in yeast-induced pyrexia mice via TLR4/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.

The oral administration of Lacticaseibacillus casei Shirota alleviates acetaminophen-induced liver injury through accelerated acetaminophen metabolism via the liver-gut axis in mice.

Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin, and hepatic cell necrosis. Moreover, LcS alleviated acetaminophen-induced intestinal mucosal permeability, decreased serum IL-1α and lipopolysaccharide levels, and elevated serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol, and sugars in the gut. Additionally, the transcriptomic and proteomic results showed that LcS mitigated the decrease in metabolic and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.IMPORTANCEAcetaminophen is the most frequently used antipyretic analgesic worldwide. As a result, overdoses easily occur and lead to drug-induced acute liver injury, which quickly progresses to liver failure with a mortality of 60%-80% if not corrected in time. The current emergency treatment for overused acetaminophen needs to be administered within 8 hours to avoid liver injury or even liver failure. Therefore, developing preventive strategies for liver injury during planned acetaminophen medication is particularly important, preferably nonpharmacological methods. Lacticaseibacillus casei Shirota (LcS) is a famous probiotic that has been used for many years. Our study found that LcS significantly alleviated acetaminophen-induced acute liver injury, especially acetaminophen-induced liver injury toward fulminant hepatic failure. Here, we elucidated the function and potential mechanisms of LcS in alleviating acetaminophen-induced acute liver injury, hoping it will provide preventive strategies to people during acetaminophen treatment.

Investigation of Anti-inflammatory, Antipyretic and Analgesic Activities of Citrullus colocynthis in Albino Rats through in vivo and Pharmacoinformatics Studies.

INTRODUCTION: Hyperpyrexia, algesia and inflammation are pathological disorders which are treated with synthetic as well as herbal medications. AIMS: The basic aim of the present study is to evaluate the ethnopharmacological activities of phytoconstituents that are present in C. colocynthis (fruit extract) by using in vivo and in silico studies. METHODS: Thirty-six albino rats were used in our studies with an average weight between 150-170 g. Anti-inflammatory activity was investigated using carrageenan (an extract from a red seaweed) that induced edema in albino rat paws. However, in antipyretic and analgesic activity studies, yeast and acetic acid were used to cause pyrexia or algesia, respectively. Different doses of acetone fruit extract were used to treat inflammation, pyrexia and algesia. RESULTS: Our results showed that the maximum percentage inhibition of acetonic fruit extract in anti-inflammatory and analgesic activities was observed at 70% and 100%, respectively, with 400 mg/kg doses, and in pyretic activity the maximum inhibitory percentage was 86% with a 100 mg/kg dose. In in silico analysis, we have shown that bioactive compounds (α-spinasterol, ascorbic acid and chlorogenic acid) found in fruit extract have outstanding inhibition properties that involves proteins PTGS2, TLR2 and TRPV4. C. colocynthis fruit extract shows results that are statistically significant (p < 0.005) and comparable to a reference drug. Acetonic fruit extract of C. colocynthis can be used as a natural and safe remedy with no side effects. CONCLUSION: Both in vivo and in silico studies on chlorogenic acid, ascorbic acid and α-spinasterol have shown that these are inhibitory compounds that can be used for boosting the immune response.

Classes of medications prescribed to malnourished children and their relationship with time to recovery.

OBJECTIVE: There is conflicting evidence around prescription practices in the management of malnutrition; the study objective was to explore medication classifications prescribed and their relationship between time-to-recovery and specific demographic characteristics among children with malnutrition in Guatemala. DESIGN: Descriptive correlational study of data obtained in a retrospective record review. SAMPLE: Children aged 0-5 years with malnutrition treated in a Guatemalan Nutrition Rehabilitation Center between 2019 and 2020 (N = 155). MEASURES: Variables assessed were medication classification of prescribed medications, age, gender, time-to-recovery, malnutrition severity, and COVID cohort. RESULTS: The most frequently used medication classifications were vitamins (95%), respiratory (75%), antipyretic (68%), antibiotic (61%), and gastrointestinal agents (54%). Antibiotic, respiratory, corticosteroid, antipyretic, and gastrointestinal agents were prescribed significantly more in cases with a time-to-recovery of 6 weeks or greater. CONCLUSIONS: Medication classifications prescribed most often were related to common comorbidities of malnutrition and illnesses affecting children in Guatemala, such as respiratory and diarrheal diseases. The medication used in cases with a time-to-recovery of ≥6 weeks suggest these cases may have had more comorbidities, which could explain the longer recovery times. Caution is suggested in routine prophylactic antibiotic use in public health settings, given the lack of association with improved recovery times, the potential for antibiotic drug resistance, and the negative effects on renal function among children.

Association between use of antipyretics and antibody titers after two doses of the BNT162b2 SARS-CoV-2 vaccine in adolescents and young adults with underlying diseases.

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (ß coefficient [95% CI] = -0.107 [-0.438 to 0.224]).

Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats.

OBJECTIVES: In Unani medicine, a comprehensive treatment plan has been delineated to deal with febrile illnesses using herbal drugs along with modified dietetics, which stands as a promising area of research. The present study was aimed at evaluating the antipyretic activity of the HAE of Artemisia absinthium L. whole plant as a standalone and as an adjuvant with barley water in an animal model of pyrexia to validate the age-old Unani principle of the treatment. METHODS: The pyrexia was induced in all the groups except the plain control using Brewer's yeast. Group II did not receive any treatment, while group III received crocin, group IV received HAE of A. absinthium, group V administered Ma al-Sha'ir, and group VI was treated with the HAE of A. absinthium along with Ma al-Sha'ir by oral route. The rectal temperature of each rat was recorded at '0' h, 30 min, 60 min, and 180 min. RESULTS: The mean rectal temperature of group III went down from 101.82±0.20 °F to 100.4±0.57 °F over the period of (0-180) minutes, whereas the mean temperature in group IV went down from 102.45±0.60 °F to 100.14±0.57 °F. The mean rectal temperature of group V decreased from 100.62±0.11 °F to 99.55±0.51 °F, while the mean rectal temperature of group VI went down from 101.95±0.1 °F to 97.7±0.11 °F. CONCLUSIONS: It is concluded that the HAE of A. absinthium L. as a standalone and along with Ma al Sha'ir showed excellent antipyretic activity as compared to the standard drug in an animal model.

Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown. OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever. MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP. RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1ß levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats. CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.