-
International Journal of Biological... Nov 2022The immunogenicity and toxicity of N-2-Hydroxypropyl trimethyl ammonium chloride chitosan/N, O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) as a universal...
The immunogenicity and toxicity of N-2-Hydroxypropyl trimethyl ammonium chloride chitosan/N, O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) as a universal vaccine adjuvant/delivery system remains unclear. The present study indicated that the positively charged N-2-HACC/CMCS NPs showed a regular spherical morphology, with a particle size of 219 ± 13.72 nm, zeta potential of 37.28 ± 4.58 mV, had hemocompatibility and biodegradation. Acute toxicity, repeated dose toxicity, abnormal toxicity, muscle stimulation, whole body allergic reaction evaluation in vitro, and cytotoxicity in vivo confirmed N-2-HACC/CMCS NPs is safe and non-toxic. N-2-HACC/OVA/CMCS NPs were prepared to evaluate the immunogenicity, which showed a particle size of 248.1 ± 15.53 nm, zeta potential of 17.24 ± 1.28 mV, encapsulation efficiency of 92.43 ± 0.96 %, and loading capacity of 42.97 ± 0.07 %. Oral or intramuscular route with the N-2-HACC/OVA/CMCS NPs in mice not only induced higher IgG, IgG1, IgG2a, and sIgA antibody titers, but also significantly produced higher levels of IL-6, IL-4, IFN-γ, and TNF-α, demonstrating that the N-2-HACC/OVA/CMCS NPs enhance humoral, cellular, and mucosal immune responses. Our results not only support the N-2-HACC/CMCS NPs to be a safe and potential universal nano adjuvant/delivery system in vaccine development, especially mucosal vaccines, but also rich the database knowledge of adjuvant/delivery systems, and provide new direction to introduce more licensed adjuvants.
Topics: Adjuvants, Immunologic; Ammonium Chloride; Animals; Chickens; Chitosan; Hypromellose Derivatives; Immunoglobulin A, Secretory; Immunoglobulin G; Interleukin-4; Interleukin-6; Mice; Nanoparticles; Tumor Necrosis Factor-alpha; Viral Vaccines
PubMed: 35981671
DOI: 10.1016/j.ijbiomac.2022.08.073 -
Methods in Molecular Biology (Clifton,... 2019Chaperone-mediated autophagy (CMA) is a selective type of autophagy whereby a specific subset of intracellular proteins is targeted to the lysosome for degradation....
Chaperone-mediated autophagy (CMA) is a selective type of autophagy whereby a specific subset of intracellular proteins is targeted to the lysosome for degradation. These proteins are identified by a chaperone that targets them to lysosomes. There, they are translocated into the organelle lumen through a lysosomal membrane receptor/translocation complex. CMA plays an important role in maintaining cellular proteostasis by eliminating damaged and altered proteins. CMA also participates in the control of the cellular energetic balance through recycling of amino acids resulting from lysosomal proteolysis of the substrate proteins. Lastly, due to the intrinsic protein selectivity of CMA, this type of autophagy exerts regulatory functions by mediating timely degradation of key cellular proteins that participate in processes such as lipid and glucose metabolism, cell cycle, DNA repair, and cellular reprogramming, among others. Dysfunctional CMA occurs with age and has now been described in a growing list of human pathologies such as metabolic disorders, neurodegeneration, cancer, immunodeficiency, and diabetes. In this chapter, we describe current methodologies to quantitatively analyze CMA activity in different experimental models.
Topics: Ammonium Chloride; Animals; Autophagy; Biological Assay; Female; Leupeptins; Liver; Lysosomes; Male; Mice; Mice, Inbred C57BL; Molecular Chaperones; Proteolysis; Rats; Rats, Wistar
PubMed: 30610733
DOI: 10.1007/978-1-4939-8873-0_47 -
Birth Defects Research Nov 2021To determine the potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) to induce reproductive toxicity in CD® rats...
AIM
To determine the potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) to induce reproductive toxicity in CD® rats in two independent 2-generation reproduction studies conducted according to Good Laboratory Practices and standardized testing guidelines.
MATERIALS AND METHODS
Male and female rats (parents and offspring) were allowed continual free access to diets containing concentrations of ADBAC (0, 300, 1,000, or 2,000 ppm) or DDAC (0, 300, 750, or 1,500 ppm), beginning with F generation adults at 10 weeks prior to breeding.
RESULTS
No clinical signs of toxicity were observed in parental rats or their offspring in either study. Dietary exposure of parental rats to ADBAC or DDAC at the highest concentrations produced transient decreases in body weight and/or body weight changes with no or minimal corresponding reduction in food consumption. Offspring (F and F ) in the highest concentration group in each study also exhibited reduced body weights, often with a corresponding reduction in weight change, beginning on postnatal day (PND) 14 through weaning on PND 28. This reduction in pup body weight corresponded to initiation of self-feeding.
CONCLUSIONS
Based on reduced body weights, the no observed adverse effect level (NOAEL) for adult and offspring systemic toxicity was 1,000 ppm for ADBAC and 750 ppm for DDAC (equivalent to approximate daily oral doses of 59 and 45 mg/kg/day, respectively). The reproductive and developmental NOAEL for F , F , and F generation male and female rats was 2,000 ppm for ADBAC and 1,500 ppm for DDAC (equivalent to approximate daily oral doses of 118 and 91 mg/kg/day, respectively).
Topics: Ammonium Chloride; Animals; Benzalkonium Compounds; Chlorides; Female; Male; No-Observed-Adverse-Effect Level; Rats; Reproduction
PubMed: 34549546
DOI: 10.1002/bdr2.1955 -
Water Research Jun 2022Hexadecyl trimethyl ammonium chloride (ATMAC-C16) is a kind of quaternary ammonium compound (QACs) which is extensively consumed as disinfectants, antimicrobials and...
Fates of quaternary ammonium compound resistance genes and the corresponding resistant strain in partial nitrification/anammox system under pressure of hexadecyl trimethyl ammonium chloride.
Hexadecyl trimethyl ammonium chloride (ATMAC-C16) is a kind of quaternary ammonium compound (QACs) which is extensively consumed as disinfectants, antimicrobials and surfactants. Here, the partial nitrification/anammox (PN/A) system was exposed to different levels of ATMAC-C16 (0-10 mg/L) and the main objective was to reveal the long-term microbiological responses of PN/A system to ATMAC-C16, importantly, explore the tolerance of PN/A to ATMAC-C16 and the key resistant strain. Nitrogen removal efficiency was influenced by environmental and extreme levels of ATMAC-C16 through mainly affecting the anammox (hzsB) gene. Two types of anammox, Candidatus Jettenia and Candidatus Kuenenia, were enriched under the pressure of ATMAC-C16, which allowed PN/A system to maintain good nitrogen removal performance. ATMAC-C16 might cause the hormesis of entire microbial population in PN/A system, leading to the enhancement of cell viability. ATMAC-C16 decreased the relative abundances of most antibiotics resistance genes (ARGs) but significantly enriched QACs resistance genes (QRGs). The tolerance of PN/A system to ATMAC-C16 might be strengthened by inducing the efflux pumps encoding genes (qacH-01/02). Microbial hosts dynamic and co-selection mechanism among ARGs and QRGs resulted in the opposite trends of qacEdeltal-01/02 and qacH-01/02. Pseudoxanthomonas mexicana was identified as the ATMAC-C16 resistant strain, and its resistance to 10 mg/L ATMAC-C16 might not only obtain by capturing the qacH gene, but also benefit from its own efflux pump system. Therefore, from the perspective of the transmission of resistance genes, especially for QRGs, the spread risk of QRGs and ATMAC-C16 resistant strain in PN/A technique should be taken seriously.
Topics: Ammonium Chloride; Ammonium Compounds; Anaerobic Ammonia Oxidation; Bioreactors; Denitrification; Nitrification; Nitrogen; Oxidation-Reduction; Quaternary Ammonium Compounds; Sewage
PubMed: 35429877
DOI: 10.1016/j.watres.2022.118395 -
International Journal of Biological... Nov 2022This is a report on the encapsulation amoxicillin (AMX) in the N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMCS)...
Amoxicillin encapsulated in the N-2-hydroxypropyl trimethyl ammonium chloride chitosan and N,O-carboxymethyl chitosan nanoparticles: Preparation, characterization, and antibacterial activity.
This is a report on the encapsulation amoxicillin (AMX) in the N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMCS) nanoparticles (NPs) for biomedical applications. The N-2-HACC/CMCS NPs have broad-spectrum antibacterial properties. In order to achieve sustained and slow drug release, improve drug transport efficiency and bioavailability, prolong drug residence time, and reduce pollution, we synthesized highly efficient, easily absorbed and rapidly degradable nano-formulation veterinary antibiotics in this study. The N-2-HACC/CMCS NPs were used for the encapsulation of AMX, and the cytocompatibility, in vitro release, in vivo drug release kinetics and antimicrobial activity of N-2-HACC/CMCS/AMX NPs were investigated. The NPs displayed a round shape and smooth surface, and the NPs allowed the sustained release of AMX at a much slower rate than that of non-coated AMX. The NPs exhibited excellent cytocompatibility and the antimicrobial activity against Escherichia coli, Acinetobacter baumannii, Streptococcus pneumoniae and Staphylococcus aureus. Moreover, the NPs could store at 4 °C, -20 °C and 25 ± 5 °C for 30 d. These results suggested that the N-2-HACC/CMCS NPs could be availed as a candidate for drug delivery carrier to achieve sustained and slow release, improve bioavailability, prolong residence time at the target site, and reduce the dosage of drug.
Topics: Chitosan; Ammonium Chloride; Amoxicillin; Nanoparticles; Drug Carriers; Anti-Bacterial Agents; Hypromellose Derivatives; Escherichia coli
PubMed: 36089095
DOI: 10.1016/j.ijbiomac.2022.09.035 -
Asian Journal of Psychiatry Nov 2023The paper describes the introduction, and early use of chemically and electrically induced convulsive therapies, at the Mysore Government Mental Hospital (MGMH), now the...
OBJECTIVE
The paper describes the introduction, and early use of chemically and electrically induced convulsive therapies, at the Mysore Government Mental Hospital (MGMH), now the National Institute of Mental Health and Neuro Sciences, Bangalore, India. Cardiazol and ammonium chloride were used at MGMH before the introduction of electroconvulsive therapy (ECT). The study examines the early history, clinical correlates and outcome of convulsive therapies and attempts to contextualize how local conditions influenced implementation.
METHOD
Three sets of archival case-records from 1938 to 1948, each of a period of 9 months following the implementation of a particular mode of convulsive therapy were reviewed.
RESULTS
During the examined timeframe, 40 patients received cardiazol, 95 ammonium chloride and 50 unmodified ECT. Schizophrenia was the commonest clinical indication for convulsive therapy across all modalities of treatment. When outcomes were examined, 45%, 48.4% and 62% of patients were clinically reported to have been either cured/improved after receiving cardiazol, ammonium chloride and ECT respectively. Those receiving cardiazol had a high mortality of 22.5%, compared to 3.1% for ammonium chloride and 4% with ECT.
CONCLUSIONS
Convulsive therapies were one of the first somatic psychiatric treatments, introduced around 1930s and 1940s all over the world, including in India. Our archival records suggest that many international ideas about somatic treatments were quickly adopted in India. Electroconvulsive therapy and other novel neuromodulatory interventions continue to be used and actively researched in India.
Topics: Humans; Hospitals, Psychiatric; Pentylenetetrazole; Ammonium Chloride; India; Convulsive Therapy; Electroconvulsive Therapy
PubMed: 37647785
DOI: 10.1016/j.ajp.2023.103747 -
Polymers May 2022Chitosan has potential applications in many fields, due to its biocompatibility, biodegradability and reproducibility. However, the insolubility in water restricts its...
Studies on Intermolecular Interaction of -Glycidyltrimethyl Ammonium Chloride Modified Chitosan/,-Dimethyl--dodecyl--(2,3-epoxy propyl) Ammonium Chloride and Curcumin Delivery.
Chitosan has potential applications in many fields, due to its biocompatibility, biodegradability and reproducibility. However, the insolubility in water restricts its wide application. In order to expand the application of chitosan in the delivery of oil-soluble drugs and improve the efficacy of oil-soluble drugs, -Glycidyltrimethyl ammonium chloride-modified chitosan (GTA-m-CS) and ,-Dimethyl--dodecyl--(1,2-epoxy propyl) ammonium chloride (DDEAC), a kind of reactive surfactant, were synthesized and characterized by FTIR, NMR and XRD methods. The interactions between GTA-m-CS and DDEAC was studied by surface tension, viscosity, conductivity and fluorescence methods. The parameters, including equilibrium surface tension, critical micelle concentrations of DDEAC with different GTA-m-CS concentration, critical aggregation concentration of DDEAC, the amount of DDEAC adsorbed on GTA-m-CS, c and were obtained from the surface tension curves. The influence of temperature on the above parameters were evaluated. The degree of counterion binding to micelle and the thermodynamic parameters of the system were calculated from the conductivity curves. According to the change of conductivity with temperature, the thermodynamic parameters of micellar formation were calculated. The aggregation number of DDEAC molecules in GTA-m-CS/DDEAC aggregates were calculated from steady-state fluorescence data. Based on the experimental results, the interaction models between GTA-m-CS and DDEAC were proposed. The GTA-m-CS/DDEAC aggregates could be used as curcumin carries, and achieved sustained release.
PubMed: 35631818
DOI: 10.3390/polym14101936 -
Biopreservation and Biobanking Jun 2022The safety of banked human adipose-derived stem cells (hADSCs) purified by 155 mM ammonium chloride (NHCl)-based erythrocyte lysis has not been evaluated. This study...
The safety of banked human adipose-derived stem cells (hADSCs) purified by 155 mM ammonium chloride (NHCl)-based erythrocyte lysis has not been evaluated. This study was conducted to determine the impact of NHCl-based erythrocyte lysis on the biological characteristics of cryopreserved hADSCs. Stromal vascular fractions (SVFs) were obtained from lipoaspirates and purified with NHCl-based erythrocyte lysis (lysis group) or without (nonlysis group). The hADSCs were freshly isolated (fresh group) from SVFs and/or cryopreserved for 2 weeks (cryo group). The morphologies, immunophenotypes, viability, apoptosis, and growth kinetics of each group were compared. The cell cycle and differentiation capacity assays were performed in both cryopreserved groups. All groups showed similar cell morphology, immunological phenotypes, and viability. However, the main effect of lysis and its interaction with cryopreservation were observed when early apoptosis was regarded as a dependent variable in two-way repeated-measures analysis of variance. After cryopreservation, significant growth retardation and S-phase fraction reduction were observed in lytic hADSCs compared with those in nonlytic hADSCs. No significant differences in the adipogenic and osteogenic differentiation capacities were found between the two groups. Although NHCl-based erythrocyte lysis did not affect the cell morphology, immunological phenotypes, viability, and adipogenic and osteogenic differentiation capacities of cryopreserved hADSCs, exposure to NHCl-based erythrocyte lysis or its synergistic action with cryopreservation may induce apoptosis and inhibit the proliferation and mitosis of cryopreserved hADSCs. These results indicate that NHCl-based erythrocyte lysis is not suitable for high-quality banked collection of hADSCs for future clinical applications. Further development of safe, convenient, and cost-effective purification methods of hADSCs is warranted.
Topics: Adipose Tissue; Ammonium Chloride; Cell Differentiation; Cells, Cultured; Erythrocytes; Osteogenesis; Stem Cells
PubMed: 34704812
DOI: 10.1089/bio.2021.0035 -
Regulatory Toxicology and Pharmacology... Oct 2020Quaternary ammonium compounds (Quats) are a large class of permanently charged cationic chemicals that are used in a variety of consumer and industrial products for... (Review)
Review
Quaternary ammonium compounds (Quats) are a large class of permanently charged cationic chemicals that are used in a variety of consumer and industrial products for their antimicrobial properties. Didecyl dimethyl ammonium chloride (DDAC) and alkyl (C12, C14, C16) dimethyl benzyl ammonium chloride (C12-C16 ADBAC) are frequently used as active ingredients in antimicrobials and are the focus of the current hazard assessment. Robust toxicology databases exist for both DDAC and C12-C16 ADBAC; however, the majority of available studies for DDAC and C12-C16 ADBAC are unpublished, but have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. With the objective of contributing to public understanding of the robust and complete toxicology database available for DDAC and C12-C16 ADBAC, a comprehensive review was conducted using available peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. A review of available literature indicates that DDAC and C12-C16 ADBAC have similar hazard profiles. Both DDAC and C12-C16 ADBAC are poorly absorbed via the oral and dermal exposure routes (≤10%), are not systemically distributed, and are primarily excreted in feces. DDAC and C12-C16 ADBAC are not dermal sensitizers, are not specific developmental or reproductive toxicants, are not carcinogenic or genotoxic, and do not cause systemic toxicity. DDAC and C12-C16 ADBAC are irritating/corrosive to skin at high concentrations, and are acutely toxic via the oral, dermal (C12-C16 ADBAC only), and inhalation exposure routes; however, both DDAC and C12-C16 ADBAC are considered non-volatile and are not readily aerosolized. Both DDAC and C12-C16 ADBAC can cause toxicity in repeated dose oral toxicity studies with no-observed-adverse-effect levels ranging from 10 to 93.1 mg/kg-day for DDAC and 3.7-188 mg/kg-day for C12-C16 ADBAC in subchronic and chronic studies conducted with beagles, mice, and rats. The toxicological effects associated with reported lowest-observed-adverse-effect levels for both DDAC and C12-C16 ADBAC are consistently characterized by reduced food consumption, reduced mean body weight, reduced body weight gain, and local irritation. These effects are consistent with the mode of action of an irritating/corrosive chemical. Based upon currently available data, the main concern associated with exposure to DDAC and C12-C16 ADBAC is local effects through irritation.
Topics: Animals; Anti-Infective Agents; Humans; Quaternary Ammonium Compounds; Risk Assessment
PubMed: 32640297
DOI: 10.1016/j.yrtph.2020.104717 -
Journal of Oleo Science Sep 2020A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (THQC) was synthesized, which consisted of one triazine spacer group and six long...
A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (THQC) was synthesized, which consisted of one triazine spacer group and six long flexible hydrophobic chains. The molecular structure and aggregation behavior of THQC was investigated by nuclear magnetic resonance (NMR), surface tension, electrical conductivity, dynamic light scattering (DLS), transmission electron microscope (TEM), etc. The results show that the jellyfish-shaped THQC has better surface activity and lower surface tension than traditional ionic and Gemini surfactants in aqueous solution. There are two inflection points in the curve of conductivity versus concentration of the THQC aqueous solution, which correspond to the critical aggregation concentration (CAC) and the critical micelle concentration (CMC) respectively. The existence of CAC indicates that there is a pre-aggregation process before THQC forms micelles. The results of DLS and TEM show that network pre-aggregation, spherical aggregation and dense spherical aggregation were observed in different concentration of THQC aqueous solution, and the electrostatic equilibrium of the system subtly depends on the concentration of the solution. In addition, intramolecular and intermolecular hydrogen bonding is also an important factor. This study provides a method for studying the aggregation behavior and morphology of oligomeric surfactants with rigid spacer groups.
Topics: Ammonium Chloride; Chemical Phenomena; Dynamic Light Scattering; Electric Conductivity; Hydrogen Bonding; Micelles; Molecular Structure; Quaternary Ammonium Compounds; Solutions; Surface Tension; Surface-Active Agents; Triazines; Water
PubMed: 32788513
DOI: 10.5650/jos.ess20016