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Biosensors Sep 2022Blood iron levels play a vital role in oxygen metabolism and energy generation whilst transporter protein, transferrin, binds and delivers iron to the transferrin...
Blood iron levels play a vital role in oxygen metabolism and energy generation whilst transporter protein, transferrin, binds and delivers iron to the transferrin receptor of endosomal compartments of cells. Consequently, the iron-binding capacity of transferrin is an important indicator for many diseases, and its measurements are used in the diagnosis and treatment of anaemias. Various assays, including Total Iron Binding Capacity (TIBC), Unsaturated Iron-Binding Capacity (UIBC) and Transferrin Saturation (TS), were developed to assess the iron-binding capacity of transferrin. Clinically, UIBC is measured in serum by a multi-step liquid ferrozine method and subjected to interference from conditions such as haemolysis and lipemia. Here, we report a quick method that directly measures the concentration of apotransferrin in EDTA-treated plasma, theoretically equivalent to UIBC. Importantly, this supramolecular assembly-based method is more time-efficient, cost-effective and insensitive to serum cation fluctuations. With additional colorimetric property, this method also provides a visual indicator for abnormal health conditions with extreme transferrin statuses such as those found in cancers. Its minimal requirement for equipment would be particularly useful for diagnosis in remote and under-developed regions.
Topics: Edetic Acid; Ferrozine; Iron; Oxygen; Receptors, Transferrin
PubMed: 36140091
DOI: 10.3390/bios12090708 -
The Journal of Toxicological Sciences 2022Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still...
Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still unclear. Here, we examined the toxicological effects of head-to-tail dimers of o-toluidine and o-anisidine, 2-methyl-N-(2-methylphenyl) benzene-1,4-diamine (MMBD) and 2-methoxy-N-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), respectively, in rats. Six-week-old male F344 rats were orally administered MMBD, MxMxBD, o-toluidine, and o-anisidine at a dose of 100 mg/kg/day for 28 days. Rats administered 400 mg/kg o-toluidine and 600 mg/kg/day o-anisidine were set as high-dose groups for comparison. Histopathology and immunohistochemistry for γ-H2AX, a DNA damage biomarker, and bladder stem cell markers, including aldehyde dehydrogenase 1A1 (ALDH1A1), were performed. MMBD and MxMxBD caused different toxicities than their monomers, inducing hepatotoxicity such as vacuolar degeneration but not splenic lesions due to methemoglobinemia. Bladder lesions, including urothelial hyperplasia, were observed in the high-dose o-toluidine and o-anisidine groups, whereas no obvious changes were induced in the low-dose groups or their dimers. Although γ-H2AX formation was significantly increased by o-toluidine and o-anisidine treatment, γ-H2AX formation did not differ among the MMBD, MxMxBD, and control groups. Notably, immunohistochemistry revealed marked increases in ALDH1A1 expression in the bladder urothelium of the MMBD and MxMxBD groups and in the o-toluidine and o-anisidine groups, suggesting that the two dimers may contribute to the bladder carcinogenic effects of o-toluidine and o-anisidine to some extent. The degrees of bladder lesions and γ-H2AX formation did not correlate with the amount of unchanged o-toluidine and o-anisidine in urine, indicating the presence of other metabolites responsible for these findings.
Topics: Rats; Male; Animals; Rats, Inbred F344; Benzene; Administration, Oral; Diamines
PubMed: 36328536
DOI: 10.2131/jts.47.457 -
Bioorganic & Medicinal Chemistry Aug 2015Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and...
Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. We previously showed that N(2),N(4)-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular Leishmania, and lead compound N(4)-(furan-2-ylmethyl)-N(2)-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis. In the present work, thirty-one N(2),N(4)-disubstituted quinazoline-2,4-diamines that had not previously been examined for their antileishmanial activity were evaluated for their potency and selectivity against Leishmania donovani, the causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with aromatic substituents at both N(2) and N(4) exhibited potent in vitro antileishmanial activity but relatively low selectivity, while compounds substituted with small alkyl groups at either N(2) or N(4) generally showed lower antileishmanial potency but were less toxic to a murine macrophage cell line. Based on their in vitro antileishmanial potency, N(4)-benzyl-N(2)-(4-chlorobenzyl)quinazoline-2,4-diamine (15) and N(2)-benzyl-N(4)-isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of their pharmacokinetic and antileishmanial properties. While 15 displayed a longer plasma half-life and a greater area under the curve than 40, both compounds showed low efficacy in an acute murine visceral leishmaniasis model. Although the present study did not identify new quinazoline-2,4-diamines with promising in vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl groups at either N(2) or N(4) may provide clues for the design of safe and effective antileishmanial quinazolines.
Topics: Animals; Antiprotozoal Agents; Diamines; Humans; Leishmania donovani; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Neglected Diseases; Quinazolines; Structure-Activity Relationship
PubMed: 25749014
DOI: 10.1016/j.bmc.2015.02.020 -
Biomacromolecules Jan 2023The reductive amination of dialdehyde cellulose (DAC) with 2-picoline borane was investigated for its applicability in the generation of bioderived thermoplastics. Five...
The reductive amination of dialdehyde cellulose (DAC) with 2-picoline borane was investigated for its applicability in the generation of bioderived thermoplastics. Five primary amines, both aliphatic and aromatic, were introduced to the cellulose backbone. The influences of the side chains on the course of the reaction were examined by various analytical techniques with microcrystalline cellulose as a model compound. The obtained insights were transferred to a 39%-oxidized softwood kraft pulp to study the thermal properties of thereby generated high-molecular-weight thermoplastics. The number-average molecular weights () of the diamine celluloses, ranging from 60 to 82 kD, were investigated by gel permeation chromatography. The diamine celluloses exhibited glass transition temperatures () from 71 to 112 °C and were stable at high temperatures. Diamine cellulose generated from aniline and DAC showed the highest conversion, the highest (112 °C), and a narrow molecular weight distribution ( of 1.30).
Topics: Amination; Amines; Cellulose; Diamines
PubMed: 36542819
DOI: 10.1021/acs.biomac.2c01022 -
Molecules (Basel, Switzerland) Sep 2022Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other... (Review)
Review
Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, β-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged -coumarinyl, 5-aryl-2-(6'-nitrobenzofuran-2'-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.
Topics: Benzothiazoles; Diabetes Mellitus, Type 2; Diamines; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Humans; Hypoglycemic Agents; Insulin; Ligands; Metformin; Oxadiazoles; Oxindoles; Thiazolidinediones
PubMed: 36144735
DOI: 10.3390/molecules27186001 -
Indian Journal of Ophthalmology Mar 2023The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating... (Review)
Review
The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating optic neuropathy in extended ethambutol use since 2010 and compared the outcome with a similar systematic review (1965-2010) by Ezer et al. Literature search was conducted in PubMed, Medline, EMBASE, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Main outcome measures were visual acuity, color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP). The JBI Critical Appraisal Checklists were used for quality assessment. Twelve studies were selected (out of 639 studies) for analysis of ethambutol optic neuropathy. Visual acuity improvement after stopping ethambutol was statistically significant. Similar improvement was not noted for other outcome measures. On comparing the results of this review with those by Ezer et al., significant improvement was noted in visual acuity, color vision, and visual field defects. Moreover, more patients reported increased optic nerve toxicity, color vision defects, and visual field defects in the present review. Hence, we conclude that the extended use of ethambutol beyond 2 months results in significant optic nerve toxicity. Further randomized controlled trials with different populations are needed to understand the magnitude of this issue.
Topics: Humans; Ethambutol; Evoked Potentials, Visual; Optic Nerve Diseases; Optic Nerve; Checklist; Rare Diseases
PubMed: 36872667
DOI: 10.4103/ijo.IJO_1920_22 -
Scientific Reports Jul 2023A one-step sandwich chemiluminescence immunometric assay (LIA) was developed for the quantification of bifunctional peptidylglycine-α-amidating monooxygenase (PAM) in...
A one-step sandwich chemiluminescence immunometric assay (LIA) was developed for the quantification of bifunctional peptidylglycine-α-amidating monooxygenase (PAM) in human plasma (PAM-LIA). PAM is responsible for the activation of more than half of known peptide hormones through C-terminal α-amidation. The assay employed antibodies targeting specific catalytic PAM-subunits, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), to ensure detection of full-length PAM. The PAM-LIA assay was calibrated with a human recombinant PAM enzyme and achieved a detection limit of 189 pg/mL and a quantification limit of 250 pg/mL. The assay demonstrated good inter-assay (6.7%) and intra-assay (2.2%) variabilities. It exhibited linearity when accessed by gradual dilution or random mixing of plasma samples. The accuracy of the PAM-LIA was determined to be 94.7% through spiking recovery experiments, and the signal recovery after substance interference was 94-96%. The analyte showed 96% stability after six freeze-thaw cycles. The assay showed strong correlation with matched EDTA and serum samples, as well as matched EDTA and Li-Heparin samples. Additionally, a high correlation was observed between α-amidating activity and PAM-LIA. Finally, the PAM-LIA assay was successfully applied to a sub-cohort of a Swedish population-based study, comprising 4850 individuals, confirming its suitability for routine high throughput screening.
Topics: Humans; Edetic Acid; Mixed Function Oxygenases; Multienzyme Complexes
PubMed: 37402878
DOI: 10.1038/s41598-023-37976-3 -
Toxicology and Industrial Health Jun 2023Performing risk assessments (RA) on household use of flexible polyurethane (PU) foams requires access to reliable data about emission and migration of potential diamine...
Performing risk assessments (RA) on household use of flexible polyurethane (PU) foams requires access to reliable data about emission and migration of potential diamine impurities. A toluene diisocyanate (TDI) and a methylene diphenyl diisocyanate (MDI) based foam were thermally treated to enable measurements on samples with defined concentrations of the corresponding diamines, toluene diamine (TDA), and methylene dianiline (MDA). The thermally treated foams used for emission testing contained up to 15 mg.kg of TDA and 27 mg.kg of MDA. Those used for migration testing contained 5.1 mg.kg of TDA and 14.1 mg.kg of MDA. Stability of the thermally generated diamines was sufficient for testing over a 37-day period. Analytical techniques that did not decompose the polymer matrix were applied. Emission rates for TDA and MDA isomers were less than the limit of quantitation (LOQ) of 0.008-0.07 μg.m.h. Migration was studied using samples of the same thermally treated foams over a 35-day period. Quantifiable migration of MDA from the MDI-based foam was only observed on Days 1 and 2. From Day 3 onward, migration rates were less than the LOQ. Quantifiable migration of TDA from the TDI-based foam rapidly decreased with time and was only observed on Days 1 thru 3. From Day 4 onward, migration rates were less than the LOQ. Theoretically, the migration rate should be inversely proportional to the square root of time (t) as t. This relationship was confirmed by the experimental data and enables extrapolating migration values to more extended time periods to conduct RAs.
Topics: Polyurethanes; Diamines; Toluene 2,4-Diisocyanate; Amines; Occupational Exposure
PubMed: 37145999
DOI: 10.1177/07482337231172816 -
RNA Biology Dec 2021Early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proven crucial during the efforts to mitigate the effects of the COVID-19...
Early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proven crucial during the efforts to mitigate the effects of the COVID-19 pandemic. Several diagnostic methods have emerged in the past few months, each with different shortcomings and limitations. The current gold standard, RT-qPCR using fluorescent probes, relies on demanding equipment requirements plus the high costs of the probes and specific reaction mixes. To broaden the possibilities of reagents and thermocyclers that could be allocated towards this task, we have optimized an alternative strategy for RT-qPCR diagnosis. This is based on a widely used DNA-intercalating dye and can be implemented with several different qPCR reagents and instruments. Remarkably, the proposed qPCR method performs similarly to the broadly used TaqMan-based detection, in terms of specificity and sensitivity, thus representing a reliable tool. We think that, through enabling the use of vast range of thermocycler models and laboratory facilities for SARS-CoV-2 diagnosis, the alternative proposed here can increase dramatically the testing capability, especially in countries with limited access to costly technology and reagents.
Topics: Benzothiazoles; COVID-19; COVID-19 Nucleic Acid Testing; DNA; DNA Primers; Diamines; Humans; Intercalating Agents; Nasopharynx; Quinolines; RNA, Viral; Real-Time Polymerase Chain Reaction; SARS-CoV-2; Sensitivity and Specificity
PubMed: 33966602
DOI: 10.1080/15476286.2021.1926648 -
Medycyna Pracy Jun 2017Toluenediamines are harmful substances. Toluene-2,4-diamine has been assigned to Carcinogen 1B hazard class, pursuant to Regulation (European Community - EC) No....
BACKGROUND
Toluenediamines are harmful substances. Toluene-2,4-diamine has been assigned to Carcinogen 1B hazard class, pursuant to Regulation (European Community - EC) No. 1272/2008 of the European Parliament and of the Council, and toluene- 2,6-diamine to Mutagen 2 hazard class. The main routes of exposure to toluene-2,4-diamine and toluene-2,6-diamine are via the respiratory tract and the skin. Toluene-2,4-diamine and toluene-2,6-diamine occur in the work environment in Poland. The aim of this study was to develop and validate a method for the determination of toluene-2,4-diamine and toluene-2,6-diamine that allows the simultaneous determination of their concentrations in the workplace air by personal sampling.
MATERIAL AND METHODS
Determination of toluene-2,4-diamine and toluene-2,6-diamine derivatives in acetonitrile were carried out by means of liquid chromatography with a diode assay detector. The method involves passing amine-containing air through sulfuric acidtreated glass fiber filter, washing out the substance settled on the filter, using water and solution of sodium hydroxide, followed by the extraction with toluene, reaction with 3,5-dinitobenzoyl chloride, replacement of dissolvent with acetonitrile and analysis of obtained solution.
RESULTS
The method developed in this study enables the researcher to determine the content of toluene-2,4-diamine and toluene-2,6-diamine in the presence of other hazardous substances. In the specified measuring range (2.88-57.6 μg/ml) calibration curves are linear. Under the optimized conditions of determination, the limit of detection (LOD) values achieved: 51.36 ng/ml for toluene-2,4-diamine and 52.93 ng/ml for toluene-2,6-diamine.
CONCLUSIONS
This method makes it possible to determine the concentration of toluene-2,4-diamine and toluene-2,6-diamine in the workplace air within the specified measuring range of 0.004-0.08 mg/m (for air sample volume of 720 l). Med Pr 2017;68(4):497-505.
Topics: Air Pollutants, Occupational; Chromatography, Liquid; Limit of Detection; Phenylenediamines
PubMed: 28584339
DOI: 10.13075/mp.5893.00552