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Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66–24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans. [ABSTRACT FROM AUTHOR]

The current study investigates the molecular interactions of glycol molecules (propylene (PG) and hexylene (HG) glycols) in hexachlorophene solutions at different temperatures and experimental pressure 0.1 MPa by merging acoustic and thermodynamic processes. The density and speed of sound of liquid mixtures are measured using an Anton Paar DSA 5000 M. These experimental values are used to calculate a variety of thermodynamic and acoustic parameters. The apparent molar volume (Vϕ), partial molar volume (Vϕ0), apparent molar isentropic compression (Kϕ,s), and partial molar isentropic compression (Kϕ,s0) are calculated with the help of experimentally determined density and speed of sound, as well as the partial molar expansibility (Eϕ0) is also calculated. The apparent molar parameters show the existence of strong interactions between solute and solvent in the ternary mixture, and it is also supported by the positive partial molar expansibility data, whereas the partial molar parameters indicate the hydrogen bonding formation in the mixture.

Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and transmitted by the bite of a sand fly. To date, most available drugs for treatment are toxic and beyond the economic means of those affected by the disease. Protein disulfide isomerase (PDI) is a chaperone protein that plays a major role in the folding of newly synthesized proteins, specifically assisting in disulfide bond formation, breakage, or rearrangement in all non-native proteins. In previous work, we demonstrated that Leishmania major PDI (LmPDI) has an essential role in pathogen virulence. Furthermore, inhibition of LmPDI further blocked parasite infection in macrophages. In this study, we utilized a computer-aided approach to design a series of LmPDI inhibitors. Fragment-based virtual screening allowed for the understanding of the inhibitors' modes of action on LmPDI active sites. The generated compounds obtained after multiple rounds of virtual screening were synthesized and significantly inhibited target LmPDI reductase activity and were shown to decrease in vitro parasite growth in human monocyte-derived macrophages. This novel cheminformatics and synthetic approach led to the identification of a new series of compounds that might be optimized into novel drugs, likely more specific and less toxic for the treatment of leishmaniasis. [ABSTRACT FROM AUTHOR]

A simple capillary electrophoresis (CE) method with ultraviolet (UV) detection was developed for the determination of hexachlorophene (HCP) in cosmetics. Separation conditions were obtained in 20 mM Na2B4O7, 10% MeOH (pH 9.20), with 25 kV applied voltage and UV detection at 208 nm. Under the selected conditions, electrophoretic analysis was completed in about 4 min, with limit of detection (LOD) of 0.06 µg·mL−1 for HCP. The method was successfully applied to determine HCP in three kinds of cosmetics with relative standard deviations (RSD) of 0.52–3.02% and recoveries from 90.0 to 96.4% for the spiked samples. The results indicated that the proposed method was reliable. Comparative experiments were also carried out with high-performance liquid chromatography (HPLC)-UV method described in National Standards of People's Republic of China. The validation results of the two methods are comparable, but the proposed CE method is simple, rapid, which makes separation and analyte quantification in shorter time with much less reagent consumption. [ABSTRACT FROM AUTHOR]

New polyomaviruses are continually being identified, and it is likely that links between this virus family and disease will continue to emerge. Unfortunately, a specific treatment for polyomavirus-associated disease is lacking. Because polyomaviruses express large Tumor Antigen, TAg, we hypothesized that small molecule inhibitors of the essential ATPase activity of TAg would inhibit viral replication. Using a new screening platform, we identified inhibitors of TAg's ATPase activity. Lead compounds were moved into a secondary assay, and ultimately two FDA approved compounds, bithionol and hexachlorophene, were identified as the most potent TAg inhibitors known to date. Both compounds inhibited Simian Virus 40 replication as assessed by plaque assay and quantitative PCR. Moreover, these compounds inhibited BK virus, which causes BKV Associated Nephropathy. In neither case was host cell viability compromised at these concentrations. Our data indicate that directed screening for TAg inhibitors is a viable method to identify polyomavirus inhibitors, and that bithionol and hexachlorophene represent lead compounds that may be further modified and/or ultimately used to combat diseases associated with polyomavirus infection.

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hexachlorophene selectively damages brain white matter. • White matter damage is easily quantified using MRI T2 relaxometry. • Partial white matter content can be mapped throughout the rat brain. • Rat brain partial white matter map is available at http://github.com/sliachenko/WMC. Segmentation of the white matter in MRI scans of the rat brain presents a significant challenge due to the low contrast. Existing anatomical reference maps of rat brain are usually constructed from fixed tissue, which may suffer from geometrical distortions due to fixation/processing. To significantly increase the in vivo contrast between white and gray matter in the rat brain we used a known neurotoxicant hexachlorophene, which produces selective white matter damage. This model was used to map white matter in the rat brain and estimate the partial white matter content in any given imaging voxel. Hexachlorophene was administered to rats at a dose of 30 mg/kg orally once a day over five consecutive days. A significant white matter changes were observed using quantitative T 2 maps, from which the partial white matter content throughout the whole rat brain was derived. Several assumptions were made: hexachlorophene affects T 2 relaxation only in the white matter; T 2 of gray matter is relatively uniform in the brain; apparent T 2 value in a given voxel is a combination of T 2 s from white and gray matter portions of that voxel, hexachlorophene affects nearly 100 % of white matter. The partial white matter map of the rat brain was constructed with the resolution of 0.2 × 0.2 × 1.0 mm per voxel. This map could be adjusted for segmentation of the brain tissue with preset threshold of the white matter content, or to establish the tissue composition in any region of interest among other applications. [ABSTRACT FROM AUTHOR]

In a previous study, we showed that 2’, 3’-Cyclic Nucleotide 3’-Phosphodiesterase (CNPase) expression is induced in different temporal patterns in the cerebrum, cerebellum and medulla oblongata of hexachlorophene (HCP) and cuprizone (CPZ) treated rats. Here, we additionally examined the histopathological changes and CNPase expression in the spinal cord to clarify the reproducibility of different temporal patterns of CNPase expression in the spinal cord showing low degree or lack of spongy changes. Spongy changes were observed in HCP-treated rats, but not in CPZ-treated rats. Immunohistochemistry showed that intense expression of CNPase was not induced following HCP or CPZ treatment. Our data reveal that expression intensity of CNPase may be dependent on the degree of HCP- and CPZ-induced damage of the myelin sheath. [ABSTRACT FROM AUTHOR]

To develop feasible probes for heavy metal ions has been considered as one of the most important research topics, due to the significance in monitoring and evaluating the toxicity of environmental water system, especially for the drinking water. This work provided a probe for Pb(II) ion detection in purified drinking water. Nickel hexacyanoferrate (NiHCF) films were prepared by vacuum evaporating nickel fine wire and transforming in a potassium ferricyanide solution on the front surface of platinum coated n-silicon. The transformed NiHCF film shows a reversible insertion electrochemistry and possesses electrocatalytic activity under illumination. The NiHCF-modified electrode was used as photoelectrode and dihydroxybenzene as photocurrent mediators to make up photoelectrochemical (PEC) sensor for Pb(II) ion detection in purified drinking water based on a two-electrode cell in absence of reference electrode and operated at zero working voltage. We have investigated the effects of Pb(II) ions on the photocurrent of hydroquinone or catechol in the purified water. The assay demonstrated good photocurrent responses by adding different concentrations of Pb(II) ion into purified drinking water with a linear range of 20-1560 nM and the limit of determination (based on S/N = 3) is 4.8 nM and 5.3 nM for the presence of hydroquinone and catechol, respectively. [ABSTRACT FROM AUTHOR]

Maternal hexachlorophene (HCP) exposure causes transient disruption of hippocampal neurogenesis in mouse offspring. We examined epigenetically hypermethylated and downregulated genes related to this HCP-induced disrupted neurogenesis. Mated female mice were dietary exposed to 0 or 100ppm HCP from gestational day 6 to postnatal day (PND) 21 on weaning. The hippocampal dentate gyrus of male offspring was subjected to methyl-capture sequencing and realtime reverse transcription-polymerase chain reaction analyses on PND 21. Validation analyses on methylation identified three genes, Dlx4, Dmrt1 and Plcb4, showing promoter-region hypermethylation. Immunohistochemically, DLX4+, DMRT1+, and PLCB4+ cells in the dentate hilus co-expressed GAD67, a γ-aminobutyric acid (GABA)ergic neuron marker. HCP decreased all of three subpopulations as well as GAD67+ cells on PND 21. PLCB4+ cells also co-expressed the metabotropic glutamate receptor, GRM1. HCP also decreased transcript level of synaptic plasticity-related genes in the dentate gyrus and immunoreactive granule cells for synaptic plasticity-related ARC. On PND 77, all immunohistochemical cellular density changes were reversed, whereas the transcript expression of the synaptic plasticity-related genes fluctuated. Thus, HCPexposed offspring transiently reduced the number of GABAergic interneurons. Among them, subpopulations expressing DLX4, DMRT1, or PLCB4 were transiently reduced in number through an epigenetic mechanism. Considering the role of the Dlx gene family in GABAergic interneuron migration and differentiation, the decreased number of DLX4+ cells may be responsible for reducing those GABAergic interneurons regulating neurogenesis. The effect on granule cell synaptic plasticity was sustained until the adult stage and reduced GABAergic interneurons active in GRM1-PLCB4 signaling may be responsible for the suppression on weaning. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC50 of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.

An efficient, simple, and fast method based on ionic liquid dispersive liquid-liquid microextraction (IL-DLLME) followed by magnetic solid-phase extraction (MSPE) was developed as a new technique for extracting and purifying hexachlorophene (HCP) in cosmetics prior to high-performance liquid chromatography (HPLC) determination. In this method based on IL-DLLME and MSPE, 1-hexyl-3-methylimidazolium hexafluorophosphate ([CMIM][PF]) is used as the extraction solvent and FeO nanoparticles are used to remove hydrophobic additives in the cosmetics by physical adsorption. The main parameters affecting the efficiency of the IL-DLLME and MSPE of HCP were investigated and optimized. Under the optimum conditions, the method was linear in the range 0.5-40 µg mL with a correlation coefficient ( R ) of 0.9976 and had a detection limit of 0.14 µg mL at a signal-to-noise ratio (S/N) of 3. The recoveries of HCP in three cosmetic samples using the proposed method were in the range 74.5-97.7%, and the relative standard deviations (RSD, n = 5) were in the range 3.8-6.7%. The developed method was successfully applied to the determination of HCP in cosmetics. [ABSTRACT FROM AUTHOR]

The emergence of severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019, has resulted in the largest pandemic in recent history. Current therapeutic strategies to mitigate this disease have focused on the development of vaccines and on drugs that inhibit the viral 3CL protease or RNA-dependent RNA polymerase enzymes. A less-explored and potentially complementary drug target is Nsp15, a uracil-specific RNA endonuclease that shields coronaviruses and other nidoviruses from mammalian innate immune defenses. Here, we perform a high-throughput screen of over 100,000 small molecules to identify Nsp15 inhibitors. We characterize the potency, mechanism, selectivity, and predicted binding mode of five lead compounds. We show that one of these, IPA-3, is an irreversible inhibitor that might act via covalent modification of Cys residues within Nsp15. Moreover, we demonstrate that three of these inhibitors (hexachlorophene, IPA-3, and CID5675221) block severe acute respiratory syndrome coronavirus 2 replication in cells at subtoxic doses. This study provides a pipeline for the identification of Nsp15 inhibitors and pinpoints lead compounds for further development against coronavirus disease 2019 and related coronavirus infections., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In the aim to determine neurotoxicity, new methods are being validated, including tests and test batteries comprising in vitro and in vivo approaches. Alternative test models such as the zebrafish (Danio rerio) embryo have received increasing attention, with minor modifications of the fish embryo toxicity test (FET; OECD TG 236) as a tool to assess behavioral endpoints related to neurotoxicity during early developmental stages. The spontaneous tail movement assay, also known as coiling assay, assesses the development of random movement into complex behavioral patterns and has proven sensitive to acetylcholine esterase inhibitors at sublethal concentrations. The present study explored the sensitivity of the assay to neurotoxicants with other modes of action (MoAs). Here, five compounds with diverse MoAs were tested at sublethal concentrations: acrylamide, carbaryl, hexachlorophene, ibuprofen, and rotenone. While carbaryl, hexachlorophene, and rotenone consistently induced severe behavioral alterations by ~ 30 h post fertilization (hpf), acrylamide and ibuprofen expressed time- and/or concentration-dependent effects. At 37-38 hpf, additional observations revealed behavioral changes during dark phases with a strict concentration-dependency. The study documented the applicability of the coiling assay to MoA-dependent behavioral alterations at sublethal concentrations, underlining its potential as a component of a neurotoxicity test battery., (© 2023. The Author(s).)

Longitudinal MRI employing diffusion tensor imaging and T 2 mapping approaches has been applied to investigate the mechanisms of white matter damage caused by acute hexachlorophene neurotoxicity in rats in vivo . Male Sprague-Dawley rats were administered hexachlorophene orally once a day for five consecutive days at a dose of 30 mg/kg and were monitored in 7T MRI scanner at days 0 (baseline), 3, 6, 13, and 20 following the first hexachlorophene dose. Quantitative T 2 maps as well as a number of diffusion tensor parameters (fractional anisotropy, radial and axial diffusivity, apparent diffusion coefficient, and trace) were calculated from corresponding MR images. T 2 , as well as all diffusion tensor derived parameters (except fractional anisotropy) showed significant changes during the course of neurotoxicity development. These changes peaked at 6 days after the first dose of hexachlorophene (one day after the last dose) and recovered to practically baseline levels at the end of observation (20 days from the first dose). While such changes in diffusivity and T 2 relaxation clearly demonstrate myelin perturbations consistent with edema, the lack of changes of fractional anisotropy suggests that the structure of the myelin sheath was not disrupted significantly by hexachlorophene in this study. This is also confirmed by the rapid recovery of all observed MRI parameters after cessation of hexachlorophene exposure. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the effects of step-wise exposure of biocide-sensitive bacteria from organic foods to phenolic biocides triclosan (TC) and hexachlorophene [2,2′-methylenebis(3,4,6-trichlorophenol)] (CF). The analysis included changes in the tolerance to the biocide itself, the tolerance to other biocides, and cross-resistance to clinically important antibiotics. The involvement of efflux mechanisms was also studied as well as the possible implication of modifications in cytoplasmic membrane fluidity in the resistance mechanisms. The influence of biocide tolerance on growth capacity of the adapted strains and on subsequent resistance to other physical stresses has also been analyzed. Repeated exposure of bacteria from organic foods to phenolic biocides resulted in most cases in partially increased tolerance to the same biocide, to dissimilar biocides and other antimicrobial compounds. Nine TC-adapted strains and six CF-adapted strains were able to develop high levels of biocide tolerance, and these were stable in the absence of biocide selective pressure. Most strains adapted to TC and one CF-adapted strain showed significantly higher anisotropy values than their corresponding wildtype strains, suggesting that changes in membrane fluidity could be involved in biocide adaptation. Exposure to gradually increasing concentrations of CF induced a decrease in heat tolerance. Biocide adaptation had no significant effects of gastric acid or bile resistance, suggesting that biocide adaptation should not influence survival in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background and Purpose: High-throughput screening of compound libraries using genetically encoded fluorescent biosensors has identified several second-generation. low MW inhibitors of the calcium-activated chloride channel anoctamin 1 (CaCC/Ano1). Here we have (i) examined the effects of these Ano1 inhibitors on gastric and intestinal pacemaker activity; (ii) compared the effects of these inhibitors with those of the more classical CaCC inhibitor, 5-nitro-2-(3-phenylpropylalanine) benzoate (NPPB); (ii) examined the mode of action of these compounds on the waveform of pacemaker activity; and (iii) compared differences in the sensitivity between gastric and intestinal pacemaker activity to the Ano1 inhibitors.Experimental Approach: Using intracellular microelectrode recordings of gastric and intestinal muscle preparations from C57BL/6 mice, the dose-dependent effects of Ano1 inhibitors were examined on spontaneous electrical slow waves.Key Results: The efficacy of second-generation Ano1 inhibitors on gastric and intestinal pacemaker activity differed significantly. Antral slow waves were more sensitive to these inhibitors than intestinal slow waves. CaCCinh -A01 and benzbromarone were the most potent at inhibiting slow waves in both muscle preparations and more potent than NPPB. Dichlorophene and hexachlorophene were equally potent at inhibiting slow waves. Surprisingly, slow waves were relatively insensitive to T16Ainh -A01 in both preparations.Conclusions and Implications: We have identified several second-generation Ano1 inhibitors, blocking gastric and intestinal pacemaker activity. Different sensitivities to Ano1 inhibitors between stomach and intestine suggest the possibility of different splice variants in these two organs or the involvement of other conductances in the generation and propagation of pacemaker activity in these tissues. [ABSTRACT FROM AUTHOR]

An outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) occurred in a college football team from August to September 2003. Eleven case-players were identified, and boils were the most common sign. Linemen had the highest attack rate (18%). Among 99 (93% of team) players with cultured specimens, 8 (8%) had positive MRSA nasal cultures. All available case-players’ MRSA isolates characterized had the community-associated pulsed-field type USA300. A case-control study found that sharing bars of soap and having preexisting cuts or abrasions were associated with infection. A carrier-control study found that having a locker near a teammate with an SSTI, sharing towels, and living on campus were associated with nasal carriage. Successful outbreak control measures included daily hexachlorophene showers and hygiene education.

Recent research highlights the importance of GSTs in the establishment of chronic helminth infections. GSTs have the potential to protect the parasite against the host immune response. In this present study, GST enzyme assay has been investigated on whole extract of F. hepatica and sheep liver tissue. To the 1-ml plastic cuvette, added 200 mM potassium phosphate buffer. Then added 50 Mm GSH reduced. Was placed the required volume of F. hepatica or sheep liver extract into the cuvette and mixed well. Added water and equilibrated at room temperature for 5 minutes. Meanwhile was set up the UV spectrophotometer at 340 nm for the GST assay. Finally was placed the cuvette into the barrel of the UV spectrophotometer and added 1-chloro-2, 4-dinitorbenzene (CDNB) and stirred well. For testing an inhibitor of GSTs such as hexachlorophene, mixed the appropriate volume of compound with GSH,reduced buffer, water and protein before equilibrating at room temperature. For calculation of IC50% value a computer package was used. The inhibitor concentration for 50% remaining activity of GSTs calculated graphically and wasobtained 10µl for F. hepatica and 20 µl for liver tissue.

3β-Hydroxysteroid dehydrogenase/steroid Δ 5,4 -isomerase 1 (3β-HSD1) plays a critical role in the biosynthesis of progesterone from pregnenolone in the human placenta to maintain normal pregnancy. Whether they inhibit placental 3β-HSD1 and mode of inhibition remains unclear. In this study, we screened 21 pesticides and fungicides in five classes to inhibit human 3β-HSD1 and compared them to rat homolog 3β-HSD4. 3β-HSD activity was measured by catalyzing pregnenolone to progesterone in the presence of NAD + . Of the 21 chemicals, azoles (difenoconazole), thiocarbamates (thiram and ferbam) and organochlorine (hexachlorophene) significantly inhibited human 3β-HSD1 with half maximal inhibitory concentration (IC 50 ) values of 2.77, 0.24, 0.68, and 17.96 μM, respectively. We also found that difenoconazole, ferbam and hexachlorophene are mixed/competitive inhibitors of 3β-HSD1 while thiram is a mixed/noncompetitive inhibitor. Docking analysis showed that difenoconazole and hexachlorophene bound steroid-binding site. Difenoconazole and hexachlorophene except thiram and ferbam also significantly inhibited rat 3β-HSD4 activity with IC 50 of 1.12 and 2.28 µM, respectively. Thiram and ferbam significantly inhibited human 3β-HSD1 possibly by interfering with cysteine residues, while they had no effects on rat 3β-HSD4. In conclusion, some pesticides potently inhibit placental 3β-HSD, leading to the reduction of progesterone formation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Hexachlorophene (HCP) has been shown to inducemyelin vacuolation due to intramyelinic edema of the nerve fibers in animal neural tissue. We investigated the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring of pregnantmice supplementedwith 0 (control), 33 or 100 ppmHCP in diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring as examined inmales exhibited decreased granule cell lineage populations expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving whitematter tracts of the hippocampal fimbria at = 33 ppm. However, SGZ cellular populations expressing brain lipid binding protein and doublecortin were unchanged at any dose. Transcript expression of cholinergic receptor genes, Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100 ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding proteinexpressing γ-aminobutyric acid (GABA)ergic interneurons in the dentate hilus, on PND 21 and PND 77. All neurogenesisrelated changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting thatmaternal HCP exposure at ≥ 33 ppm reversibly decreased type 2 intermediate-stage progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be responsible for changes in neurogenesis possibly by reducing nerve conduction velocity of cholinergic inputs from the septal-hippocampal pathway to granule cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to granule cell lineages. [ABSTRACT FROM AUTHOR]

The electrical properties and ac conductivity of the bis tetra-propylammonium hexachloro-dizincate have been investigated by means of impedance spectroscopy measurements in the 209 Hz-5 MHz frequency range and 303-403 K temperature interval. The Nyquist plots are fitted to an equivalent circuit modeled by a combination of a parallel bulk resistance and constant phase elements. The experimental results indicate that σ(ω) is proportional to (ω). It was found that s increases by increasing temperature below the phase transition at 327 ± (5) K (region I) and decrease with increasing temperature above 327 ± (5) (region II). An agreement between the experimental and theoretical results are discussed and suggests that the ac conductivity can be explained by the non overlapping small polaron tunneling model and correlated barrier hopping in region I and II, respectively. Furthermore, the modulus plots can be characterized by full width at half height or in terms of a non-experiential decay function $$\varPhi \left( {\text{t}} \right) = \exp \left( {\frac{{ - {\text{t}}}}{\tau }} \right)^{\beta }$$ . [ABSTRACT FROM AUTHOR]

TAR DNA binding protein (TDP43) is a DNA- and RNA-binding protein that is implicated in several neurodegenerative disorders termed as “TDP43 proteinopathies” including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and fronto-temporal lobe dementia (FTLD). We have developed an InCell Western (ICW) technique for screening TDP targeting drugs in 96 well plates. We tested 281 compounds and identified a novel compound hexachlorophene (referred to as B10) that showed potent reduction in TDP43 levels. The effect of B10 on TDP protein level was validated in two different cellular models: endogenous TDP43 expressing N9 microglial cells and TDP43-over-expressing HEK293 and HeLa cells. We also analyzed effect of B10 on various pathological forms of TDP such as the C25 cleaved fragment that localizes to the cytosol, insoluble high molecular weight species, and ALS-linked mutants. Our data suggest that B10 effectively reduces all forms of TDP. Overall, our data suggest that B10 could serve as a potential drug molecule for the treatment of AD, ALS and other TDP43 proteinopathies. [ABSTRACT FROM AUTHOR]

Background: HIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI). However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons. Methods: 550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban) twice daily and hexachlorophene (pHisoHex) soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point. Results: Forty-nine (9%) HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized), 67% were negative for MRSA colonization in both groups (p = 1.0). Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35). There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89). In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point. Conclusion: A one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in this population. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 ( Chrnb2 ) and B-cell CLL/lymphoma 2 ( Bcl2 ) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction of cholinergic inputs into granule cell lineages and/or GABAergic interneurons as indicated by decreased transcript levels of Chrnb2 and numbers of Chrnb2 + interneurons caused by myelin vacuolation in the septal–hippocampal pathway. [ABSTRACT FROM AUTHOR]

The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/ KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC50 of 4.61±29 mM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics. [ABSTRACT FROM AUTHOR]

The article discusses a research study which found that hexachlorophene and cuprizone induce the spongy change of the developing rat brain by different mechanisms and investigated the role of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) expression in neutrotoxicity. The materials and methods used in the study are described. The mortality and clinical sings, histopathologic, immunohistochemical and electron microscopic findings are discussed.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for 35% of the genetic alterations in non-small cell lung cancer (NSCLC). The Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11 , is closely involved in RAS downstream pathways and development of many tumors by affecting cell proliferation, differentiation, and immunity. Targeting SHP2 with small molecules may be a promising avenue for the treatment of KRAS -mutant (mut) NSCLC. Herein, hexachlorophene (HCP) was identified as a SHP2 inhibitor with an IC 50 value of 5.63 ± 0.75 μM through screening of the FDA-approved drug library. HCP specifically inhibited SHP2 rather than other phosphatases. Molecular docking showed that HCP displayed an orientation favorable for nucleophilic attack in the catalytic domain of SHP2. HCP suppressed viability of multiple KRAS -mut and KRAS -wild type cells and induced senescence and apoptosis in KRAS -mut cells. Moreover, HCP reversed epithelial-mesenchymal transition to suppress metastasis in KRAS -mut cells, and inhibited the RAS/MEK/ERK and PI3K/AKT signaling pathways by suppression of SHP2 phosphorylation and formation SHP2/Grb2/Gab1/SOS1 complex. In summary, HCP can act as a specific SHP2 inhibitor to inhibit KRAS -mut NSCLC cell proliferation and metastasis and induce senescence through suppression of the RAF/MEK/ERK and PI3K/AKT pathways. HCP warrants further investigation as a new compound skeleton for the development of selective SHP2 inhibitors for the treatment of NSCLC. • HCP selectively inhibits the enzymatic activity of SHP2. • HCP inhibits growth and metastasis in KRAS -mut NSCLC cells. • HCP inhibits the RAS/MAPK and PI3K/AKT signaling pathways in KRAS -mut NSCLC cells. • HCP disrupts the SHP2/Grb2/Gab1/SOS1 complex in KRAS -mut NSCLC cells. [ABSTRACT FROM AUTHOR]

Abstract: Many studies have shown that the activation of β-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein–Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause increases in the expression of β-catenin and cellular transformation. Conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlorophene can down-regulate β-catenin in colon cancer cells. Here we report that hexachlorophene also counteracts the elevated β-catenin levels in EBV-infected B lymphomas. This is associated with restoration in levels of Siah-1 (an E3 ubiquitin ligase that is active in β-catenin regulation) which had been diminished by LMP-1. Our results suggest that Siah-1 is targeted by both LMP-1 and hexachlorophene with opposite effects. The hexachlorophene modulation of Siah-1 and β-catenin is independent of p53 and results in reduced expression of cyclin-D1 and c-Myc (target genes of β-catenin), leading to the growth arrest of B lymphoma cells. From these results we propose that hexachlorophene may provide a novel therapeutic strategy for EBV-infected B lymphoma cells by reducing β-catenin levels via the restoration of Siah-1. [Copyright &y& Elsevier]

Abstract: Examinations of brain of rats intoxicated with hexachlorophene or acrylamide with ultrahigh-field (4.7T) proton magnetic resonance (MR) showed alterations consistent with clinical pictures in humans and morphological findings in experimental animals. On the other hand, conventional biochemical analyses have revealed that ethylene oxide, methyl bromide, and acrylamide inhibit creatine kinase (CK; an enzyme catalyzing the reaction: ATP+creatine↔ADP+phosphocreatine) activities in the brain of animals. Thus, 31P MR combined with magnetization transfer may be utilized to monitor living humans (or animals) intoxicated with these chemicals by determining CK activities in the target organ. [Copyright &y& Elsevier]

Abstract: SARS-CoV 3CL protease is essential for viral protein processing and is regarded as a good drug target to prevent SARS-CoV replication. In the present study, we established a high-throughput FRET technique for screening for anti-SARS-CoV 3CL protease drugs. Of a thousand existing drugs examined, hexachlorophene was identified as the most potent in inhibiting SARS-CoV 3CL protease. Further characterization showed that it was effective at micromolar concentrations (K i =4μM). The binding mode was competitive, and the inhibitory effect was dependent on preincubation time. Two other drugs, triclosan and nelfinavir, were about 10 times less potent. The structure-based search and biological evaluation of various hexachlorophene analogues were described. These analogues gave optimal inhibitory activity against SARS-CoV 3CL protease with IC50 values ranging from 7.6 to 84.5μM. Optimization of hexachlorophene analogues was shown to provide several active 3CL protease inhibitors that function as potential anti-SARS agents. [Copyright &y& Elsevier]

We examined the anti-estrogenic activity of 50 chemicals by the yeast two-hybrid assay and detected the activity of hexachlorophene, pentachlorophenol, and vitamin K3 (menadione), in that order. These chemicals were also observed to inhibit the transcriptional activity of 17β-estradiol in a reporter gene assay system using MCF-7 cells, estrogen receptor-positive breast cancer cells, and to bind directly to estrogen receptor α in a competitive binding assay system, although the order of the activity was slightly different among the 3 assays. These findings suggested that three of fifty chemicals could inhibit estrogen activity by competitive binding with 17β-estradiol to the estrogen receptor. [Copyright &y& Elsevier]

Hexachlorophene is primarily used as an antiseptic in germicidal soaps but can be toxic if absorbed through the skin. Rotation of its benzene rings about the two central methyl bonds gives rise to a variety of minima characterized by intramolecular hydrogen bonding. Triclosan is an antibacterial currently used in a wide range of consumer goods, from drugs to hand soaps. With the emerging resistance of bacteria to triclosan, researchers now consider hexachlorophene as a possible option in the design of antibacterial drugs. Clinical studies have demonstrated that these two molecules, though comparable in structure, bind to different adjacent sites in bacterial Enoyl-ACP Reductase (FabI), which is used in fatty acid synthesis. This significant discovery is attributed to subtle structural disparities between the two compounds. Determination of the conformations adopted in vitro and in vivo is crucial in elucidating the binding mechanism of these two compounds. Ab initio structural analyses have been performed on these two molecules using gaussian98 software. [Copyright &y& Elsevier]

N-methyl-D-aspartate (NMDA) and non-NMDA receptors were found to be involved in development of functional disorders caused by hexachlorophene. In order to specify the role of glutamate receptors we studied the protective effects of the selective antagonist of the kainate/(±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor/channel 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide disodium (NBQX) and of the non-competitive NMDA receptor antagonist ifenprodil tartrate on coordinative motor behaviour of adult male Wistar rats as assessed in a simple `ladder-test'. Neurotoxic injury of the cerebrum after hexachlorophene administration and putative amelioration after treatment with test substances was demonstrated histologically. Hexachlorophene-induced motor disturbance remitted spontaneously when stopping the noxis, but remittance occurred significantly earlier when NBQX [0.45 and 0.6 mg/kg intraperitoneal (i.p.)] was applied as well. Ifenprodil (0.15 to 1.2 mg/kg) did not improve the motor function. Vacuolation of white matter of the whole cerebrum was observed after 3 weeks of treatment with hexachlorophene. These morphological alterations caused by hexachlorophene treatment [central nervous system (CNS) vacuolation] spontaneously revert only after 5–6 weeks. The 5-day duration with test substances was too short for remission of vacuolation which thus may not apply to the situation after treatment with glutamate antagonists, despite improvement of motor function. The results suggest that kainate/AMPA receptor channels are at least partially involved in the mechanism of brain damage induced by hexachlorophene, however, the polyamine binding site of the NMDA receptor evidently is not involved. [ABSTRACT FROM AUTHOR]

Abstract We previously reported that myelin-associated oligodendrocytic basic protein (MOBP) was abundantly expressed in the central nervous system (CNS) myelin, and shared several characteristics with myelin basic protein (MBP). In particular, a cluster of positively charged amino acids was considered to facilitate compaction of the cytoplasmic face of the myelin sheath, as in the case of MBP. However, the contribution of MOBP in forming and maintaining the myelin sheath still remains unclear. Recent investigations showed that one isoform of MOBP was expressed in the embryo prior to myelination, and MOBP isoforms were colocalized with the microtubular network and nucleus in vitro. To explore the role of MOBP in vivo, we generated MOBP-deficient mice and analysed the CNS myelin. Surprisingly, the compact myelin was formed, however, the myelin from MOBP-deficient mice exposed to hexachlorophene, a known dysmyelinating agent, showed widening of the major dense lines. These results suggest that MOBP is not essential for myelin formation, but reinforces the apposition of the cytoplasmic faces of the myelin sheath. A striking phenotype of MOBP-deficient mice was the presence of the straight ‘condensed' radial component. This component has been described as a tight junction-like complex running radially and zig-zag through the CNS myelin sheath between inner and outer mesaxons. These results suggest that MOBP is essential for normal arrangement of the radial component. [ABSTRACT FROM AUTHOR]

Focuses on a study that assessed the susceptibility of human beings to the neurotoxic effects of hexachlorophene demonstrated in experimental animals. Methods; Results; Discussion.

Handwashing is generally considered the most important procedure in preventing nosocomial infections, because many types of these infections may be caused by organisms transmitted on the hands of personnel. Personnel should wash their hands before and after significant contact with any patient. The risk of personnel acquiring transient hand carriage of organisms is usually greatest after contact with excretions, secretions, or blood; patients at greatest risk are those undergoing surgery, those with catheters, and newborn infants. Although handwashing with an antiseptic agent between patient contacts is theoretically desirable, handwashing with soap, water, and mechanical friction are sufficient ro remove most transiently acquired organisms. Antiseptic agents may produce excessively dry skin if used frequently, and any regimen of handwashing that leads to dermatitis negates the purpose of handwashing. We favor antiseptics for handwashing before surgery and other high-risk invasive procedures and in the care of newborn infants but prefer soap and water for other handwashing. [ABSTRACT FROM AUTHOR]

The diverse, structurally unrelated chemicals that cause toxic myelinopathies have been investigated and can be categorized into two types of primary demyelinators. Some demyelinating chemicals seem to leave intact the myeli-nating cells (oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system), while others damage the myelinating cells as well as the myelin. The significance between the two is that with the myelinating cells still in tact, repair of the myelin sheath can occur. However, if the myelinating cells are destroyed, repair and reversal of the neuropathy may not occur. Histologically, these chemicals produce an edema of the white matter of the brain, and in some cases the peripheral nervous system, that appears spongy by light microscopy. By electron microscopy, vacuoles can be seen in the myelin surrounding axons. These vacuoles are characterized as fluid-filled separations (splitting) of myelin lamellae at the intraperiod line. In some cases these vacuoles can degenerate further to full demyelination, affecting conduction through those axons. Regeneration of the myelin layers can occur, and in some cases occurs at the same time other axons are undergoing toxic demyelination. Several of these chemicals, however, have been shown to increase cerebrospinal fluid pressure in the brain, optic nerve, and spinal cord, and/or intraneuronal pressure in the perineurium surrounding the axons in the peripheral nervous system. This increased pressure has been correlated with decreased conduction capacity through the axon, ischemia to the neuronal tissue from decreased blood flow because of pressure against the blood vessels, and, if unrelieved, permanent axonal damage. Several of these chemicals havebeen shown to inhibit oxidative phosphorylation, while others uncouple oxidative phosphorylation. One chemical appears to inhibit an enzyme critical to cholesterol synthesis, thus destabilizing myelin. Another hypothesis for a mechanism of action may be in the ability of these compounds to alter membrane permeability. [ABSTRACT FROM PUBLISHER]

Presents a study which examined the influence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo in children. Materials and methods; Results; Discussion.

Discusses regulations of the U.S. Federal Drug Administration (FDA) on hexachlorophene used as a topical bacteriostatic agent against Staphylococcus aureus. Comments on FDA hexachlorophene position paper.

Hexachlorophene is highly effective in the control of colonization and disease with Staphylococcus aureus in both normal and high risk nurseries, when properly used, including correct cord and skin care. However, much more about this compound needs to be known, particularly more about the metabolism in the human, absorption, excretion, body storage, tissue distribution, and so forth. [ABSTRACT FROM AUTHOR]

Six patients exposed to 3% hexachlorophene were studied. Two were adults that had accidentaly ingested a large amount of the substance. The remaining were children, two of which were being treated with 3% hexachlorophene baths for burns and two for severe congenital ichthyosis. The two adults developed symptoms shortly after ingestion and died in less than 48 hours. The interval between exposure and symptoms in the children ranged from six hours to ten days. All the children showed severe vacuolation of the white matter in different areas of the cerebrum as well as the cerebellum. In the two adults no vacuolation of the white matter was evident. [ABSTRACT FROM AUTHOR]

The published data on the toxicity of hexachlorophene in animals and man are discussed. Studies performed in the author's laboratory including hexachlorophene blood level determinations in animals and man are also reviewed. Hexachlorophene can produce paralysis in rats, rabbits, cats, and pigs and blindness in sheep. Microscopic examination of the brains of rats and monkeys given repeated doses of hexachlorophene shows status spongiosus of the white matter and normal gray matter. Small amounts of hexachlorophene are absorbed through the skin of animals as well as man. Aside from the neurological effects of hexachlorophene, the chemical uncouples oxidative phosphorylation which may cause body temperature elevation. [ABSTRACT FROM AUTHOR]

During an 8-week period beginning February 11, 1972, 33 infants, born at the Boston City hospital, developed disease due to Group A, type 28, Steptococcus pyogenes. The administration of parenteral benzathin penicillin G to full term infants and oral penicillin V to low birth weight infants was effective in preventing subsequent infection and disease. Concurrently, bacteriologic surveys indicated extensive colonization of newborn infants with Staphylococcus aureus. A double blind study of hexachlorophene compared with detergent base bathing the prevention of staphylococcal infection and disease of the newborn infants was instituted. The diaper area including the umbilical stump was washed. The bathing procedure was instituted soon after delivery and once each day during the hospitalization and at home to complete a 3-week course. A surveillance system, including home visits during the third week of life, was established. Although a few infants with staphylococcal disease were diagnosed in the nursery, most infants with pustules, omphalitis, and conjunctivitis were identified through the home visit. Colonization rates of Staphylococcus aureus were similar in the two groups. Staphylococcal disease was significantly decreased in the hexachlorophene-bathed infants during the first 11 weeks of the study. [ABSTRACT FROM AUTHOR]

This paper reports the occurrence and control of staphylococcal sepsis in 35,684 infants born in a maternity unit in Geelong, Australia, during the years 1956 to 1972. Antiseptic skin care of newborn infants with 3% hexachlorophene emulsions (pHisoHex) commenced in 1960 and since then 25,038 infants have been drywashed with 3% hexachlorophene emulsions on alternate days while in hospital with no toxic reactions. A retrospective review of the macroscopic and microscopic findings in 233 neonatal and post neonatal deaths occurring in these 25,038 infants did not reveal any evidence of central nervous system damage as described due to hexachlorophene in animals. A "double-blind" study of 10,001 infants showed that hexachlorophene was the effective agent responsible for the marked reduction in infant and maternal staphylococcal sepsis which occurred in this maternity unit following the introduction of drywashing in 1960. No increase in clinical infection due to gram-negative bacilli is reported since the commencement of drywashing newborn infants with 3% hexachlorophene emulsions. Infant plasma hexachlorophene concentrations on the day prior to discharge home from hospital varied from 0.020 µg/ml to a maximum of 0.150 µg/ml. The Australian Drug Evaluation Committee accepted a strong recommendation from the author in March 1971, that antiseptic skin care of newborn infants with 3% hexachlorophene emulsions should continue in maternity hospitals in Australia. [ABSTRACT FROM AUTHOR]

Hexachlorophene (HCP) is used in a range of general cleaning and disinfecting products and has received increased attention due to its damaging effect to the central nervous system in animals and its toxicity in humans. The chemical oxidation of HCP by KMnO 4 was performed to systematically evaluate the effects of oxidant dose, pH, temperature, typical anions, humic acid (HA), and various matrices on HCP removal. The second-order rate constant for HCP was determined to be 4.83 × 104 M−1 s−1 at pH 7.0 and 25 °C. The presence of HA can inhibit the removal of HCP by KMnO 4 , while Cl−, NO 3 −, SO 4 2−, PO 4 3−, and CO 3 2− have negligible effects. Degradation products analysis of the reaction, as well as theoretical calculations of HCP molecule and its phenoxy radical species, indicated that KMnO 4 oxidation for HCP included a C–C bridge bond cleavage, hydroxylation, direct oxidation and self-coupling, and cross-coupling reactions. This study revealed that KMnO 4 oxidation is an effective technique for eliminating HCP in real water and wastewater. Image 1 • The degradation processes of HCP by KMnO 4 were systematically studied. • Seventeen intermediates of HCP were detected by LC-Q-TOF-MS. • The oxidation of HCP mainly involves C–C bridge bond cleavage, hydroxylation, direct oxidation and coupling reactions. • Density functional theory was employed to determine the reaction sites of HCP. [ABSTRACT FROM AUTHOR]

We investigated the synthesis of N-docosahexaenoylethanolamine (synaptamide) in neuronal cells from unesterified docosahexaenoic acid (DHA) or DHA-lysophosphatidylcholine (DHA-lysoPC), the two major lipid forms that deliver DHA to the brain, in order to understand the formation of this neurotrophic and neuroprotective metabolite of DHA in the brain. Both substrates were taken up in Neuro2A cells and metabolized to N-docosahexaenoylphosphatidylethanolamine (NDoPE) and synaptamide in a time- and concentration-dependent manner, but unesterified DHA was 1.5 to 2.4 times more effective than DHA-lysoPC at equimolar concentrations. The plasmalogen NDoPE (pNDoPE) amounted more than 80% of NDoPE produced from DHA or DHA-lysoPC, with 16-carbon-pNDoPE being the most abundant species. Inhibition of N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) by hexachlorophene or bithionol significantly decreased the synaptamide production, indicating that synaptamide synthesis is mediated at least in part via NDoPE hydrolysis. NDoPE formation occurred much more rapidly than synaptamide production, indicating a precursor–product relationship. Although NDoPE is an intermediate for synaptamide biosynthesis, only about 1% of newly synthesized NDoPE was converted to synaptamide, possibly suggesting additional biological function of NDoPE, particularly for pNDoPE, which is the major form of NDoPE produced. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC50 of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity. [ABSTRACT FROM AUTHOR]

In a previous study, we showed that 2', 3'-Cyclic Nucleotide 3'-Phosphodiesterase (CNPase) expression is induced in different temporal patterns in the cerebrum, cerebellum and medulla oblongata of hexachlorophene (HCP) and cuprizone (CPZ) treated rats. Here, we additionally examined the histopathological changes and CNPase expression in the spinal cord to clarify the reproducibility of different temporal patterns of CNPase expression in the spinal cord showing low degree or lack of spongy changes. Spongy changes were observed in HCP-treated rats, but not in CPZ-treated rats. Immunohistochemistry showed that intense expression of CNPase was not induced following HCP or CPZ treatment. Our data reveal that expression intensity of CNPase may be dependent on the degree of HCP- and CPZ-induced damage of the myelin sheath.