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Skinmed 2023A-24-year-old woman reported with asymptomatic facial lesions present for 6 months. Examination revealed two closely located nodules which were firm, nontender, slightly...
A-24-year-old woman reported with asymptomatic facial lesions present for 6 months. Examination revealed two closely located nodules which were firm, nontender, slightly erythematosus with crusting over the left cheek (Figure 1A). There was no regional lymphadenopathy, and the systemic examination was within normal limits. The differential diagnosis included cutaneous leishmaniasis, keratoacanthoma, and basal cell carcinoma. Tissue smear from nodules failed to reveal bodies. The histopathologic examination revealed nonca-seating epithelioid granulomas with lymphocyte cuffing in the dermis (Figures 2A and 2B). Special staining performed with Ziehl-Neelsen and Periodic acid-Schiff (PAS) stains was negative. Tissue cultures for bacteria, mycobacteria, and fungi were also negative; however Mantoux test (MT) performed for latent tuberculosis was strongly positive. Sputum for acid fast bacilli was negative, and serology for human immuno-deficiency virus (HIV)-1 and HIV-2 was nonreactive. A chest x-ray and ultrasound of the abdomen did not reveal any abnormality. Although the morphology of skin lesions did not favor classic lupus vulgaris (LV), considering the endemicity of tuberculosis in India, positive results of Mantoux test, and a dermal epithelioid granuloma, the patient was prescribed antitubercular therapy (ATT), comprising isoniazid, rifampicin, ethambutol, and pyrazinamide. Dramatic response was observed after 2 months, and complete healing with residual scarring took place in next 4 months (Figure 1B).
Topics: Female; Humans; Antitubercular Agents; Ethambutol; Isoniazid; Pyrazinamide; Skin Neoplasms
PubMed: 38051246
DOI: No ID Found -
Physics in Medicine and Biology Apr 2024To evaluate the reduction in energy dependence and aging effect of the lithium salt of pentacosa-10,-12-diynoic acid (LiPCDA) films with additives including aluminum...
To evaluate the reduction in energy dependence and aging effect of the lithium salt of pentacosa-10,-12-diynoic acid (LiPCDA) films with additives including aluminum oxide (AlO), propyl gallate (PG), and disodium ethylenediaminetetracetate (EDTA).. LiPCDA films exhibited energy dependence on kilovoltage (kV) and megavoltage (MV) photon energies and experienced deterioration over time. Evaluations were conducted with added AlOand antioxidants to mitigate these issues, and films were produced with and without AlOto assess energy dependence. The films were irradiated at doses of 0, 3, 6, and 12 cGy at photon energies of 75 kV, 105 kV, 6 MV, 10 MV, and 15 MV. For the energy range of 75 kV to 15 MV, the mean and standard deviation (std) were calculated and compared for the values normalized to the net optical density (netOD) at 6 MV, corresponding to identical dose levels. To evaluate the aging effect, PG and disodium EDTA were incorporated into the films: sample C with 1% PG, sample D with 2% PG, sample E with 0.62% disodium EDTA added to sample D, and sample F with 1.23% disodium EDTA added to sample D.. Films containing AlOdemonstrated a maximum 15.8% increase in mean normalized values and a 15.1% reduction in std, reflecting a greater netOD reduction at kV than MV energies, which indicates less energy dependence in these films. When the OD of sample 1-4 depending on the addition of PG and disodium EDTA, was observed for 20 weeks, the transmission mode decreased by 8.7%, 8.3%, 29.3%, and 27.3%, respectively, while the reflection mode was 5.4%, 3.0%, 37.0%, and 34.5%, respectively.. AlOeffectively reduced the voltage and MV energy dependence. PG was more effective than disodium EDTA in preventing the deterioration of film performance owing to the aging effect.
Topics: Film Dosimetry; Aluminum Oxide; Edetic Acid; Propyl Gallate; Photons
PubMed: 38565123
DOI: 10.1088/1361-6560/ad39c1 -
Dalton Transactions (Cambridge, England... Aug 2023The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor...
The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor 2-propylpentanoic acid or valproic acid, VPA, and the potential antimetastatic molecule 4-isopropenylcyclohexene-1-carboxylic acid or perillic acid, PA) in order to obtain a set of multiaction or multitarget antiproliferative agents. In addition to traditional thermal synthetic procedures, microwave-assisted heating was used to speed up their preparation. All Pt(IV) complexes showed antiproliferative activity on four human colon cancer cell lines (namely HCT116, HCT8, RKO and HT29) in the nanomolar range, considerably better than those of [PtCl(cyclohexane-1,2-diamine)], VPA, PA, and the reference drug oxaliplatin. The synthesized complexes showed pro-apoptotic and pro-necrotic effects and the ability to induce cell cycle alterations. Moreover, the downregulation of histone deacetylase activity, leading to an increase in histone H3 and H4 levels, and the antimigratory activity, indicated by the reduction of the levels of matrix metalloproteinases MMP2 and MMP9, demonstrated the multiaction nature of the complexes, which showed biological properties similar to or better than those of VPA and PA, but at lower concentrations, probably due to the lipophilicity of the combo molecule that increases the intracellular concentration of the single components (, [PtCl(cyclohexane-1,2-diamine)], VPA and PA).
Topics: Platinum; Prodrugs; Diamines; Valproic Acid; Colonic Neoplasms; Humans; Cell Line, Tumor; Histone Deacetylases; Cell Movement; Antineoplastic Agents
PubMed: 37530512
DOI: 10.1039/d3dt01876h -
Molecules (Basel, Switzerland) Oct 2023This study describes the development of two highly sensitive immunosensor platforms for the trace determination of copper ions, Cu(II), in drinking water. These...
Development and Comparative Evaluation of Two Highly Sensitive Immunosensor Platforms for Trace Determination of Copper Ions in Drinking Water Using a Monoclonal Antibody Specific to Copper-EDTA Complex.
This study describes the development of two highly sensitive immunosensor platforms for the trace determination of copper ions, Cu(II), in drinking water. These platforms were a microwell-based enzyme-linked immunosorbent assay (ELISA) and a kinetic exclusion assay (KinExA) with a KinExA 3200 immunosensor. Both ELISA and KinExA were developed utilizing the same antibody and coating reagent. The antibody was a mouse monoclonal antibody, designated as 8D66, that specifically recognized Cu(II)-ethylenediamine tetraacetic acid complex (Cu(II)-EDTA) but did not recognize Cu(II)-free EDTA. The 8D66 monoclonal antibody was generated by the fusion of spleen cells of an immunized BALB/c mouse with SP2/0-Ag14 myeloma cells. The immunogen was a protein conjugate of Cu(II)-EDTA with keyhole limpet hemocyanin protein. The coating reagent was Cu(II)-EDTA covalently linked to bovine serum albumin protein (Cu(II)-EDTA-BSA). Both assays involved the competitive binding reaction between Cu(II)-EDTA complexes, formed in the sample solution, and Cu(II)-EDTA-BSA conjugate which has been immobilized onto ELISA plates (in ELISA) or polymethylmethacrylate beads (in KinExA) for a limited quantity of binding sites of the 8D66 antibody. In ELISA, color signals were generated by a peroxidase-labeled secondary antibody and 3,3',5,5'-tetramethylbenzidine substrate. In KinExA, a fluorescein isothiocyanate-labeled secondary antibody was used to generate KinExAgram (trend-line fluorescence responses vs. time). The conditions of both ELISA and KinExA were investigated, and the optimum procedures were established. Both ELISA and KinExA were validated, and all validation parameters were acceptable. Many different metal ions that are commonly encountered in drinking water did not interfere with the Cu(II) analysis by both ELISA and KinExA. Both assays were applied to the determination of Cu(II) in drinking water with satisfactory accuracy and precision. Both assays were compared favorably with inductively coupled plasma atomic emission spectroscopy in terms of their abilities to accurately and precisely determine Cu(II) in drinking water samples. A comparative evaluation of ELISA and KinExA revealed that KinExA had a higher sensitivity and better precision than ELISA, whereas both assays had comparable accuracy. Both ELISA and KinExA were superior to the existing atomic spectrometric methods for Cu(II) in terms of sensitivity, convenience, and analysis throughputs. The proposed ELISA and KinExA are anticipated to effectively contribute to assessing Cu(II) concentrations and control the exposure of humans to its potential toxicities.
Topics: Humans; Animals; Mice; Copper; Antibodies, Monoclonal; Edetic Acid; Drinking Water; Biosensing Techniques; Immunoassay; Antigens; Indicators and Reagents
PubMed: 37894495
DOI: 10.3390/molecules28207017 -
Scientific Reports Nov 2023The present study aimed to investigate the possible use of a non-instrumentation technique including blue light irradiation for root canal cleaning. Extracted human...
The present study aimed to investigate the possible use of a non-instrumentation technique including blue light irradiation for root canal cleaning. Extracted human single rooted teeth were selected. Nine different groups included distilled water, NaOCl, intra-canal heated NaOCl, and NaOCl + EDTA irrigation after either instrumentation or non-instrumentation, and a laser application group following non-instrumentation technique. The chemical assessment of the root canal dentine was evaluated using energy dispersive spectroscopy (EDS) and Fourier transform infrared (FT-IR) spectroscopy. Surface microstructural analyses were performed by using scanning electron microscopy (SEM). The antimicrobial efficacy of different preparation techniques was evaluated using microbial tests. Light application didn't change the calcium/phosphorus, carbonate/phosphate and amide I/phosphate ratios of the root canal dentin. The root canal dentin preserved its original chemistry and microstructure after light application. The instrumentation decreased the carbonate/phosphate and amide I/phosphate ratios of the root canal dentin regardless of the irrigation solution or technique (p < 0.05). The application of light could not provide antibacterial efficacy to match the NaOCl irrigation. The NaOCl irrigation both in the non-instrumentation and instrumentation groups significantly reduced the number of bacteria (p < 0.05). The use of minimally invasive root canal preparation techniques where the root canal is not instrumented and is disinfected by light followed by obturation with a hydraulic cement sealer reduced the microbial load and preserved the dentin thus may be an attractive treatment option for management of vital teeth needing root canal therapy.
Topics: Humans; Spectroscopy, Fourier Transform Infrared; Dentin; Root Canal Therapy; Phosphates; Carbonates; Amides; Root Canal Irrigants; Edetic Acid; Sodium Hypochlorite; Microscopy, Electron, Scanning
PubMed: 37990070
DOI: 10.1038/s41598-023-47682-9 -
Nature Communications Oct 2023The broad bioactivities of nonribosomal peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029...
The broad bioactivities of nonribosomal peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029 leads to the identification of a class of dodecapeptides, glidonins, that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus. The N-terminal diversity originates from the wide substrate selectivity of the initiation module. The C-terminal putrescine moiety is introduced by the unusual termination module 13, the condensation domain directly catalyzes the assembly of putrescine into the peptidyl backbone, and other domains are essential for stabilizing the protein structure. Swapping of this module to another two nonribosomal peptide synthetases leads to the addition of a putrescine to the C-terminus of related nonribosomal peptides, improving their hydrophilicity and bioactivity. This study elucidates the mechanism for putrescine addition and provides further insights to generate diverse and improved nonribosomal peptides by introducing a C-terminal putrescine.
Topics: Putrescine; Peptides; Peptide Synthases
PubMed: 37857663
DOI: 10.1038/s41467-023-42387-z -
Bioorganic Chemistry Dec 2023New benzimidazole-1,2,3-triazole-quinoline hybrids and their intermediates, differing in substitutions at the C-2 and/or C6 positions of the benzimidazole ring, were...
Synthesis, characterization, in vitro antimycobacterial and cytotoxicity evaluation, DFT calculations, molecular docking and ADME studies of new isomeric benzimidazole-1,2,3-triazole-quinoline hybrid mixtures.
New benzimidazole-1,2,3-triazole-quinoline hybrids and their intermediates, differing in substitutions at the C-2 and/or C6 positions of the benzimidazole ring, were successfully synthesized in 55---80 % yields, with the C6-substituted ones forming as inseparable tautomeric mixtures. The synthesized compounds were fully characterised by FT-IR, 1D- and 2D-NMR, and HRMS. In-depth NMR analysis and DFT molecular calculations showed that the tautomeric mixtures formed in a ratio of almost 1:1 ratio (cis and trans), except for 5 g, where the ratio is 1:2. In vitro antimycobacterial activity evaluation against the H37Rv strain of Mycobacterial tuberculosis was undertaken on all synthesized compounds, and a selected number were further screened for their cytotoxicity on TZM-bl cell lines. Hybrid compounds showed excellent MIC activities ranging from 1.07 to 8.66 μM and were all more efficacious than the first-line reference drug, ethambutol (MIC = 9.54 μM). In particular, hybrid compounds 5b (MIC = 1.54 μM, CC = 58.89 μM and % cell viability = 14.07), 5d (MIC = 2.08 μM, CC = 0.27 μM, and % cell viability = 149.50 %) and 5 g (MIC = 1.49 μM, CC = 4.62 μM and % cell viability = 44.03) were the most promising. Significantly, 5b and 5 g were over six times more efficacious than ethambutol but exhibited cytotoxicity towards TZM-bl cell-lines compared to 5d, which was over four times more active than ethambutol. The physical combination (mimicking combination therapy) of individual pharmacophoric components making up 5 g were less active, indicating the synergistic effect of hybridization. In addition, more than 60 % of all the synthesized hybrids showed better activity than their respective pharmacophoric components. In silico ADME studies of the hybrids revealed favourable physico-chemical properties, while molecular modeling studies suggested binding interactions with Val 61, Gly 62, Glu 65, Ala 66, and Phe 69 amino acid in a reported similar manner to bedaquiline, an approved quinoline-based anti-TB drug.
Topics: Molecular Docking Simulation; Structure-Activity Relationship; Ethambutol; Triazoles; Density Functional Theory; Spectroscopy, Fourier Transform Infrared; Microbial Sensitivity Tests; Anti-Bacterial Agents; Benzimidazoles; Quinolines; Molecular Structure
PubMed: 37832224
DOI: 10.1016/j.bioorg.2023.106904 -
Letters in Applied Microbiology Aug 2023The purpose of this study was to evaluate the antimicrobial activity of indole-3-carbinol (I3C) with membrane-active agents, namely carbonyl cyanide...
The purpose of this study was to evaluate the antimicrobial activity of indole-3-carbinol (I3C) with membrane-active agents, namely carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and ethylenediaminetetraacetic acid (EDTA) against multidrug-resistant (MDR) Gram-negative bacteria and bacterial persisters. The determination of minimal inhibitory concentration (MIC) showed that I3C was effective against Acinetobacter baumannii (3.13‒6.25 × 10-3 mol l-1), Klebsiella pneumoniae (8 × 10-3 mol l-1), Pseudomonas aeruginosa (6.25‒12.5 × 10-3 mol l-1), and Escherichia coli (6.25‒12.5 × 10-3 mol l-1). Our study demonstrated that EDTA synergistically enhanced the bactericidal activity of I3C against most MDR Gram-negative bacteria isolates and contributed to an 8- to 64-fold MIC reduction compared with that of I3C alone, yet CCCP only displayed synergy with I3C against P. aeruginosa and A. baumannii. The EDTA-I3C combination also significantly reduced the viable number of testing bacteria (P = 7.2E-05), effectively reduced bacterial persisters, and repressed bacterial growth compared with that the use of I3C alone. Our data demonstrate that use of EDTA as adjuvant molecules can effectively improve the antibacterial activity of I3C and may help to reduce the development of antimicrobial resistance.
Topics: Edetic Acid; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Drug Synergism; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Bacteria; Gram-Negative Bacteria; Microbial Sensitivity Tests
PubMed: 37580156
DOI: 10.1093/lambio/ovad093 -
Analytical Chemistry Nov 2023Amine determination is crucial to our daily life, including the prevention of pollution, the treatment of certain disorders, and the evaluation of food quality. Herein,...
Amine determination is crucial to our daily life, including the prevention of pollution, the treatment of certain disorders, and the evaluation of food quality. Herein, a mixed-linkage donor-acceptor covalent organic framework (named DSE-COF) was first constructed by the polymerization between 2,4-dihydroxybenzene-1,3,5-tricarbaldehyde (DTA) and 4,4'-(benzo[][1,2,5]selenadiazole-4,7-diyl)dianiline (SEZ). DSE-COF displayed superior turn-on fluorescent responses to primary, secondary, and tertiary aliphatic amines, such as cadaverine, isopropylamine, -butylamine, cyclohexylamine, hexamethylenediamine, di--butylamine, and triethylamine in absolute acetonitrile than other organic species. Further experiments and theoretical calculations demonstrated that the combination of intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) effects between the DSE-COF and aliphatic amines resulted in enhanced fluorescence. Credibly, DSE-COF can quantitatively detect cadaverine content in actual pork samples with satisfactory results. In addition, DSE-COF-based test papers could rapidly monitor cadaverine from real pork samples, manifesting the potential application of COFs in food quality inspection.
Topics: Humans; Cadaverine; Metal-Organic Frameworks; Amines; Cyclohexylamines; Cockayne Syndrome; Coloring Agents
PubMed: 37967038
DOI: 10.1021/acs.analchem.3c03985 -
The Journal of Experimental Biology Oct 2023Fossorial Damaraland mole-rats (Fukomys damarensis) mount a robust hypoxic metabolic response (HMR) but a blunted hypoxic ventilatory response (HVR) to acute hypoxia....
Fossorial Damaraland mole-rats (Fukomys damarensis) mount a robust hypoxic metabolic response (HMR) but a blunted hypoxic ventilatory response (HVR) to acute hypoxia. Although these reflex physiological responses have been described previously, the underlying signalling pathways are entirely unknown. Of particular interest are contributions from γ-aminobutyric acid (GABA), which is the primary inhibitory neurotransmitter in the nervous system of most adult mammals, and adenosine, the accumulation of which increases during hypoxia as a breakdown product of ATP. Therefore, we hypothesized that GABAergic and/or adenosinergic signalling contributes to the blunted HVR and robust HMR in Damaraland mole-rats. To test this hypothesis, we injected adult animals with saline alone (controls), or 100 mg kg-1 aminophylline or 1 mg kg-1 bicuculline, to block adenosine or GABAA receptors, respectively. We then used respirometry, plethysmography and thermal RFID probes to non-invasively measure metabolic, ventilator and thermoregulatory responses, respectively, to acute hypoxia (1 h in 5 or 7% O2) in awake and freely behaving animals. We found that bicuculline had relatively minor effects on metabolism and thermoregulation but sensitized ventilation such that the HVR became manifest at 7% instead of 5% O2 and was greater in magnitude. Aminophylline increased metabolic rate, ventilation and body temperature in normoxia, and augmented the HMR and HVR. Taken together, these findings indicate that adenosinergic and GABAergic signalling play important roles in mediating the robust HMR and blunted HVR in Damaraland mole-rats.
Topics: Animals; Bicuculline; Aminophylline; Adenosine; Mole Rats; Hypoxia; gamma-Aminobutyric Acid
PubMed: 37694288
DOI: 10.1242/jeb.246186