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Antioxidants (Basel, Switzerland) May 2024Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote,...
Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.
PubMed: 38929087
DOI: 10.3390/antiox13060648 -
International Journal of Environmental... Jun 2024This study assessed three powdered activated carbons (BETM, COCO, and SIAL) commercialized in Brazil at the bench scale in agitated reactors, analyzing their kinetic...
This study assessed three powdered activated carbons (BETM, COCO, and SIAL) commercialized in Brazil at the bench scale in agitated reactors, analyzing their kinetic behavior and adsorptive capacity for BPS and BPA in ultrapure water. BETM exhibited the highest adsorption capacities (Q) for BPS and BPA at 260.62 and 264.64 mg/g, respectively, followed by SIAL, with a Q of 248.25 mg/g for BPS and for 231.20 mg/g BPA, and COCO, with a Q of 136.51 mg/g for BPS and 150.03 mg/g for BPA. The Langmuir isotherm model can describe the processes well. A pseudo-second-order model can describe the adsorption kinetics, and SIAL carbon had the highest rate constants (7.45 × 10 mg/g/min for BPS and 2.84 × 10 mg/g/min for BPA). The Weber-Morris intraparticle diffusion model suggests intraparticle diffusion as the rate-limiting step of all adsorption processes. Boyd's model confirmed more than the mechanism actuating in the bisphenol adsorption. The results suggest that adsorbents with basic surfaces, high specific surface areas, and high mesopore volumes tend to remove BPS and BPA efficiently. Therefore, activated carbons can effectively complement the existing treatment in Brazilian water treatment plants (WTPs).
Topics: Phenols; Adsorption; Brazil; Charcoal; Water Pollutants, Chemical; Sulfones; Water Purification; Kinetics; Benzhydryl Compounds
PubMed: 38929038
DOI: 10.3390/ijerph21060792 -
International Journal of Molecular... Jun 2024Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood...
Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood purification therapies such as cardiovascular surgery and dialysis. The anticoagulant effect of heparin is essential for the optimal execution of extracorporeal blood circulation. However, at the end of these procedures, to avoid the risk of bleeding, it is necessary to neutralize it. Currently, the only antidote for heparin neutralization is protamine sulphate, a highly basic protein which constitutes a further source of serious side events and is ineffective in neutralizing LMWH. Furthermore, dialysis patients, due to the routine administration of heparin, often experience serious adverse effects, among which HIT (heparin-induced thrombocytopenia) is one of the most severe. For this reason, the finding of new heparin antagonists or alternative methods for heparin removal from blood is of great interest. Here, we describe the synthesis and characterization of a set of biocompatible macroporous cryogels based on poly(2-hydroxyethyl methacrylate) (pHEMA) and -lysine with strong filtering capability and remarkable neutralization performance with regard to UFH and LMWH. These properties could enable the design and creation of a filtering device to rapidly reverse heparin, protecting patients from the harmful consequences of the anticoagulant.
Topics: Heparin; Humans; Cryogels; Anticoagulants; Lysine; Heparin, Low-Molecular-Weight; Heparin Antagonists
PubMed: 38928208
DOI: 10.3390/ijms25126503 -
BMC Plant Biology Jun 2024Microplastic (MP) pollution in terrestrial ecosystems is gaining attention, but there is limited research on its effects on leafy vegetables when combined with heavy...
Microplastic (MP) pollution in terrestrial ecosystems is gaining attention, but there is limited research on its effects on leafy vegetables when combined with heavy metals. This study examines the impact of three MP types-polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS)-at concentrations of 0.02, 0.05, and 0.1% w/w, along with cadmium (Cd) and biochar (B), on germination, growth, nutrient absorption, and heavy metal uptake in red amaranth (Amaranthus tricolor L.). We found that different MP types and concentrations did not negatively affect germination parameters like germination rate, relative germination rate, germination vigor, relative germination vigor, and germination speed. However, they increased phytotoxicity and decreased stress tolerance compared to an untreated control (CK1). The presence of MPs, particularly the PS type, reduced phosphorus and potassium uptake while enhancing Cd uptake. For example, treatments PSCdB, PSCdB, and PSCdB increased Cd content in A. tricolor seedlings by 158%, 126%, and 44%, respectively, compared to the treatment CdB (CK2). Additionally, MP contamination led to reduced plant height, leaf dry matter content, and fresh and dry weights, indicating adverse effects on plant growth. Moreover, the presence of MPs increased bioconcentration factors and translocation factors for Cd, suggesting that MPs might act as carriers for heavy metal absorption in plants. On the positive side, the addition of biochar improved several root parameters, including root length, volume, surface area, and the number of root tips in the presence of MPs, indicating potential benefits for plant growth. Our study shows that the combination of MPs and Cd reduces plant growth and increases the risk of heavy metal contamination in food crops. Further research is needed to understand how different MP types and concentrations affect various plant species, which will aid in developing targeted mitigation strategies and in exploring the mechanisms through which MPs impact plant growth and heavy metal uptake. Finally, investigating the potential of biochar application in conjunction with other amendments in mitigating these effects could be key to addressing MP and heavy metal contamination in agricultural systems.
Topics: Amaranthus; Cadmium; Charcoal; Microplastics; Soil Pollutants; Germination; Nutrients; Seedlings
PubMed: 38926861
DOI: 10.1186/s12870-024-05312-0 -
Environmental Monitoring and Assessment Jun 2024Modification is widely used to enhance the adsorption performance of pristine hydrochar (HBC) and pyrochar (BC). However, comparisons between modified HBC and BC toward...
Effect of citric acid modification on the properties of hydrochar and pyrochar and their adsorption performance toward methylene blue: crucial roles of minerals and oxygen functional groups.
Modification is widely used to enhance the adsorption performance of pristine hydrochar (HBC) and pyrochar (BC). However, comparisons between modified HBC and BC toward pollutant removal have rarely been reported. In this study, pristine HBC and BC derived from rice straw were first produced, and then citric acid (CA) was used as a modifier to synthesize CA-modified HBC (CAHBC) and CA-modified BC (CABC). Furthermore, the adsorption performance of biochars toward methylene blue (MB) was investigated. The results showed that BC exhibits relatively rough surfaces and contains more minerals (ash), whereas HBC has plentiful O-containing functional groups and fewer minerals. CA modification partially removed minerals from the surface of BC, which weakened the ion exchange, surface complexation, and n-π interaction, resulting in a lower adsorption ability toward MB. By contrast, CA produced more O-containing functional groups on the surface of HBC, which strengthened the hydrogen bonding and electrostatic interaction, thus increasing the adsorption capacity toward MB. The two-compartment model showed a good fit to the adsorption process of MB on CAHBC, and the isotherm data for MB adsorption by HBC and CAHBC are suitable for the Freundlich model. The highest adsorption amount of MB using CAHBC was 80.13 mg·g, which was 27.66% higher than that for CABC. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis indicated that the carboxyl groups in the surface functional groups of CAHBC played a crucial role in the MB adsorption process. In addition, CAHBC showed a good performance for a wide range of pH values (4.0-10.0) and under the interference of coexisting ions, and also presented a recycling ability. Furthermore, the adsorption of MB on CAHBC biochar was a spontaneous, exothermic, degree-of-randomness-increasing process. Consequently, CA modification of HBC is a promising strategy and could be used for MB removal from aquatic environments.
Topics: Methylene Blue; Adsorption; Citric Acid; Charcoal; Water Pollutants, Chemical; Minerals; Oxygen
PubMed: 38926195
DOI: 10.1007/s10661-024-12836-3 -
British Journal of Clinical Pharmacology Jun 2024Serotonin syndrome (toxicity), resulting from an excessive accumulation of serotonin in the central nervous system, it can occur due to various factors such as the... (Review)
Review
Serotonin syndrome (toxicity), resulting from an excessive accumulation of serotonin in the central nervous system, it can occur due to various factors such as the initiation of medication, overdose or drug interactions. Diagnosing serotonin toxicity presents challenges as there are no definitive criteria. This review delves into the pathophysiology, incidence, clinical assessment and management of serotonin toxicity, stressing the significance of promptly recognizing and managing severe cases. Diagnosis relies primarily relies on clinical assessment due to the absence of specific laboratory tests. The Hunter Serotonin Toxicity criteria are commonly utilized but have only been validated in the overdose setting. Assessing the severity of toxicity is crucial for guiding management decisions. Supportive care, discontinuation of causative agents and symptomatic treatment are prioritized in management. Mild toxicity often requires withdrawal or reduction of the serotonergic agent, while more severe toxicity requires more aggressive resuscitative and supportive care. Severe serotonin toxicity characterized by hyperthermia and rigidity requires aggressive supportive measures, including benzodiazepines, intubation, paralysis and active cooling. Animal studies suggest potential benefits of 5-HT2A receptor antagonists in preventing hyperthermia and fatalities, but only at high doses. Their clinical effectiveness remains uncertain, and evidence is predominately from case series and case reports. Although commonly used, serotonin antagonists like cyproheptadine lack conclusive evidence of efficacy. Other serotonin antagonists such as chlorpromazine and olanzapine have been explored but evidence is limited to case reports. Hence, the cornerstone of treating severe cases does not lie in 'antidote' administration or even diagnosis but in effective early resuscitative and supportive care.
PubMed: 38926083
DOI: 10.1111/bcp.16152 -
British Journal of Clinical Pharmacology Jun 2024Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to... (Review)
Review
Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.
PubMed: 38926082
DOI: 10.1111/bcp.16142 -
Toxics May 2024From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to... (Review)
Review
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
PubMed: 38922056
DOI: 10.3390/toxics12060376 -
Biosensors May 2024Glucosamine-chitosan synthesized by the Maillard reaction was combined with montmorillonite to obtain a nanohybrid composite to immobilize horseradish peroxidase. The...
Glucosamine-chitosan synthesized by the Maillard reaction was combined with montmorillonite to obtain a nanohybrid composite to immobilize horseradish peroxidase. The material combines the advantageous properties of clay with those of the chitosan derivative; has improved water solubility and reduced molecular weight and viscosity; involves an eco-friendly synthesis; and exhibits ion exchange capacity, good adhesiveness, and a large specific surface area for enzyme adsorption. The physicochemical characteristics of the composite were analyzed by infrared spectroscopy and X-ray diffraction to determine clay-polycation interactions. The electrochemical response of the different polyphenols to glassy carbon electrodes modified with the composite was evaluated by cyclic voltammetry. The sensitivity and detection limit values obtained with the biosensor toward hydroquinone, chlorogenic acid, catechol, and resorcinol are (1.6 ± 0.2) × 10 µA mM and (74 ± 8) nM; (1.2 ± 0.1) × 10 µA mM and (26 ± 3) nM; (16 ± 2) µA mM and (0.74 ± 0.09) μM; and (3.7± 0.3) µA mM and (3.3 ± 0.2) μM, respectively. The biosensor was applied to quantify polyphenols in pennyroyal and lemon verbena extracts.
Topics: Bentonite; Biosensing Techniques; Polyphenols; Chitosan; Horseradish Peroxidase; Enzymes, Immobilized; Electrochemical Techniques; Glucosamine; Electrodes
PubMed: 38920582
DOI: 10.3390/bios14060278 -
Rhode Island Medical Journal (2013) Jul 2024The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell... (Review)
Review
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Topics: Humans; Pancreatic Neoplasms; Female; Aged; Adenocarcinoma; Triazoles; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Pyrimidines; Mutation; Antineoplastic Agents; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin; Off-Label Use; Piperazines; Pyridines
PubMed: 38917307
DOI: No ID Found