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Scientific Reports Mar 2022Visible-light-driven photo-fenton-like catalytic activity and photoelectrochemical (PEC) performance of nitrogen-doped brownmillerite KBiFeO (KBFO) are investigated....
Visible-light-driven photo-fenton-like catalytic activity and photoelectrochemical (PEC) performance of nitrogen-doped brownmillerite KBiFeO (KBFO) are investigated. The effective optical bandgap of KBFO reduces from 1.67 to 1.60 eV post N-doping, enabling both enhancement of visible light absorption and photoactivity. The photo-fenton activity of KBFO and N-doped KBFO samples were analysed by degrading effluents like Methylene Blue (MB), Bisphenol-A (BPA) and antibiotics such as Norfloxacin (NOX) and Doxycycline (DOX). 20 mmol of Nitrogen-doped KBFO (20N-KBFO) exhibits enhanced catalytic activity while degrading MB. 20N-KBFO sample is further tested for degradation of Bisphenol-A and antibiotics in the presence of HO and chelating agent L-cysteine. Under optimum conditions, MB, BPA, and NOX, and DOX are degraded by 99.5% (0.042 min), 83% (0.016 min), 72% (0.011 min) and 95% (0.026 min) of its initial concentration respectively. Photocurrent density of 20N-KBFO improves to 8.83 mA/cm from 4.31 mA/cm for pure KBFO. Photocatalytic and photoelectrochemical (PEC) properties of N-doped KBFO make it a promising candidate for energy and environmental applications.
Topics: Anti-Bacterial Agents; Catalysis; Hydrogen Peroxide; Light; Methylene Blue; Nitrogen
PubMed: 35332159
DOI: 10.1038/s41598-022-08966-8 -
Cell Death & Disease Dec 2023Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the...
Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug's ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.
Topics: Humans; Glioblastoma; Chlorpromazine; Pyruvate Kinase; Cell Line, Tumor; Energy Metabolism
PubMed: 38092755
DOI: 10.1038/s41419-023-06353-3 -
Journal of B.U.ON. : Official Journal... 2020In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular... (Review)
Review
In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine's addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950's. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.
Topics: Dopamine Antagonists; Glioblastoma; Humans; Perphenazine
PubMed: 33099901
DOI: No ID Found -
Clinical Medicine (London, England) Sep 2020Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest...
Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue.
Topics: Dapsone; Humans; Methemoglobinemia; Methylene Blue
PubMed: 32934050
DOI: 10.7861/clinmed.2020-0364 -
International Journal of Environmental... Oct 2022The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of...
The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.
Topics: Male; Humans; Adult; Methemoglobinemia; Methylene Blue; Anemia, Hemolytic; Pyridines; Neurotoxicity Syndromes; Poisoning
PubMed: 36360910
DOI: 10.3390/ijerph192114031 -
Journal of Enzyme Inhibition and... Dec 2023Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming...
Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII.
Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming increasingly important in the biomedical field since enhancing CA activity may have beneficial effects at neurological level. Here, we investigate selected antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants (TCAs) as potential activators of human CAs I, II, IV, and VII. Our findings indicate that these compounds are more effective at activating hCA II and VII compared to hCA I and IV. Overall, hCA VII was the most efficiently activated isoform, particularly by phenothiazines and TCAs. This is especially relevant since hCA VII is the most abundant isoform in the central nervous system (CNS) and is implicated in neuronal signalling and bicarbonate balance regulation. This study offers additional insights into the pharmacological profiles of clinically employed drugs and sets the ground for the development of novel optimised CAAs.
Topics: Humans; Antipsychotic Agents; Antidepressive Agents, Tricyclic; Carbonic Anhydrases; Protein Isoforms; Phenothiazines; Histamine Antagonists; Carbonic Anhydrase Inhibitors; Structure-Activity Relationship; Molecular Structure
PubMed: 36912265
DOI: 10.1080/14756366.2023.2188147 -
Indian Journal of Pathology &... 2023The Fine needle aspiration cytology (FNAC) is considered as a valuable and distinguished diagnostic test in the initial assessment of the patients presenting with a mass...
BACKGROUND
The Fine needle aspiration cytology (FNAC) is considered as a valuable and distinguished diagnostic test in the initial assessment of the patients presenting with a mass in the head and neck region or when a recurrence is suspected after previous treatment.
AIMS
This study was therefore designed to elucidate the efficacy of FNAC as an alternate diagnostic tool to histopathology in head and neck swellings and evaluation of staining efficacy of PAP and MGG stain over Haematoxylin and eosin (H and E) in routine cytopathological smears.
SETTINGS AND DESIGN
The study was conducted in the Department of Oral and Maxillofacial Pathology, where FNAC samples were collected from 150 patients with head and neck swellings.
MATERIALS AND METHODS
All the slides were stained with H and E, Papanicolaou (PAP), and May Grunewald Giemsa (MGG) stains. The cytopathological diagnosis was compared with histopathological diagnosis based on H and E stained sections obtained from paraffin-embedded formalin-fixed biopsy specimen of benign and malignant neoplasms.
STATISTICAL ANALYSIS USED
The resulting data were analyzed using SPSS software version 19. Differences between the variables were analyzed using Pearson Chi-square test and Kruskal-Wallis test wherever applicable.
RESULTS
The FNAC as a diagnostic tool has sensitivity of 84.8%, 72.72%, and 78.78%, specificity of 62.5%, 75%, and 75%, and accuracy of 80.48%, 73.14%, and 78.04% in H and E, MGG, and PAP stain, respectively. PAP stain was the most efficient stain when all qualitative parameters are taken into consideration with maximum sensitivity and specificity for achieving definitive cytodiagnosis.
CONCLUSIONS
The FNAC is an inexpensive and minimally invasive technique to diagnose different types of head and neck swellings and complement histopathological diagnosis.
Topics: Humans; Coloring Agents; Pathology, Oral; Staining and Labeling; Neck; Cytological Techniques; Azure Stains; Hematoxylin
PubMed: 37530331
DOI: 10.4103/ijpm.ijpm_1254_21 -
Antiviral Research Jul 2021Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to...
Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives.
Topics: Antiviral Agents; Cell Line; Cowpox virus; HeLa Cells; Humans; Methylene Blue; Monkeypox virus; Orthopoxvirus; Vaccinia virus; Virus Attachment
PubMed: 33992710
DOI: 10.1016/j.antiviral.2021.105086 -
Current Eye Research Mar 2023Intraocular pressure (IOP) is an important factor in numerous ocular conditions and research areas, including eye growth and myopia. In infant monkeys, IOP is typically...
PURPOSE
Intraocular pressure (IOP) is an important factor in numerous ocular conditions and research areas, including eye growth and myopia. In infant monkeys, IOP is typically measured under anesthesia. This study aimed to establish a method for awake IOP measurement in infant rhesus monkeys, determine diurnal variation, and assess the effects of dilation and sedation.
METHODS
Awake IOP (iCare TonoVet) was measured every 2 h from 7:30 am to 5:30 pm to assess potential diurnal variations in infant rhesus monkeys (age 3 weeks, = 11). The following day, and every 2 weeks to age 15 weeks, IOP was measured under three conditions: (1) awake, (2) awake and dilated (tropicamide 0.5%), and (3) sedated (ketamine and acepromazine) and dilated. Intraclass correlation coefficient (ICC) was used to determine intersession repeatability, and repeated measures. ANOVA was used to determine effects of age and condition.
RESULTS
At age 3 weeks, mean (±SEM) awake IOP was 15.4 ± 0.6 and 15.2 ± 0.7 mmHg for right and left eyes, respectively (=.59). The ICC between sessions was 0.63[-0.5 to 0.9], with a mean difference of 2.2 ± 0.3 mmHg. Diurnal IOP from 7:30 am to 5:30 pm showed no significant variation (=.65). From 3 to 15 weeks of age, there was a significant effect of age (=.01) and condition (<.001). Across ages, IOP was 17.8 ± 0.7 mmHg while awake and undilated, 18.4 ± 0.2 mmHg awake and dilated, and 11.0 ± 0.3 mmHg after sedation and dilation.
CONCLUSIONS
Awake IOP measurement was feasible in young rhesus monkeys. No significant diurnal variations in IOP were observed between 7:30 am and 5:30 pm at age 3 weeks. In awake monkeys, IOP was slightly higher after mydriasis and considerably lower after sedation. Findings show that IOP under ketamine/acepromazine anesthesia is significantly different than awake IOP in young rhesus monkeys.
Topics: Animals; Intraocular Pressure; Macaca mulatta; Ketamine; Acepromazine; Dilatation; Tonometry, Ocular; Glaucoma, Open-Angle; Anesthesia
PubMed: 36357337
DOI: 10.1080/02713683.2022.2141782 -
Contact Dermatitis Jul 2020In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter...
BACKGROUND
In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter (OTC) for the treatment of mosquito bites and pruritus in France.
OBJECTIVE
To report a series of cases with photodermatitis following use of topical phenothiazines.
METHOD
A retrospective study of cases of contact dermatitis from phenothiazines seen in French photodermatology centers was performed.
RESULTS
In all, 14 patients with a diagnosis of contact dermatitis from phenothiazines were included. These patients developed eczema on the application sites, and in 13 the eruption spread to photodistributed sites. Topical products containing isothipendyl were the most common cause of photodermatitis. One patient had photoaggravated eczema due to promethazine cream. All patients stopped using topical phenothiazines and were treated successfully with topical corticosteroids. One patient relapsed and developed persistent light eruption. In all of the nine cases tested, photopatch testing to the topical phenothiazine used "as is" was positive. Isothipendyl, chlorproethazine, and the excipients were not tested. Photopatch tests to chlorpromazine and promethazine were positive in 8 of 12 and 7 of 13 tested, respectively.
CONCLUSION
Use of isothipendyl and promethazine as OTC (or even prescribed) drugs needs to be limited due to severe reactions and sensitization to other phenothiazines that consequently will have to be avoided.
Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Chlorpromazine; Dermatitis, Photoallergic; Female; Histamine Antagonists; Humans; Male; Middle Aged; Phenothiazines; Promethazine; Thiazines
PubMed: 32124458
DOI: 10.1111/cod.13509