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A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzod imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good ...yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by ‘one-pot’ nitro reductive cyclization reaction between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using sodium dithionite in dimethylsulfoxide. This ‘one-pot’ reaction was proceeded very smoothly, in short reaction time with an excellent yield. All the compounds (7a–r) were screened for their in vivo anti-inflammatory and in vitro antimicrobial activity. Most of the compounds exhibited remarkable paw-edema inhibition in the initial one hour of administration indicating the higher potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g displayed a high level of carrageenan-induced paw edema inhibition compared to that of indomethacin. Compound 7p exhibited very good antibacterial activity and antifungal activity with a MIC of 3.12μg/mL against most of the tested organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors of Aspergillus niger with MIC of 3.12μg/mL. Cytotoxicity of the potent compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and are found to be non toxic at the highest concentration used (i.e., 10μg/mL).
Novel piperamide bearing 4-hydroxypiperidine as antidepressant and antioxidant agent.
A series of piperamide derivatives (8a–j) was synthesized with various substituted piperidine and piperazine ...compounds. The prepared compounds were evaluated for antibacterial activity against gram-positive and gram-negative bacteria and antifungal activity by disc diffusion method. The antioxidant activity of the compounds was evaluated by DPPH and superoxide radical scavenging method and antidepressant activity using forced swim and tail suspension behavioral despair tests in mice. The compounds 8a, 8b and 8c were investigated for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory property. Some of the test compounds were active in forced swim test (FST) and tail suspension test (TST). Compounds 8a and 8b showed a significant effect, when compared to standard drug, clorgyline.
Summary
The Glidescope® is a new videolaryngoscope. It has a digital camera incorporated in the blade which displays a view of the vocal cords on a monitor. This allows the placement of a tracheal ...tube to be visualised. We describe its performance in 50 patients who required orotracheal intubation for elective surgery. Two investigators performed 25 intubations each. Intubation with the Glidescope® was successful in 47 of the 50 cases. The three failures occurred early in the series and were attributed to the initial learning curve. The success rate after the first eight patients in each series was 100%. The median (IQR range) time to intubation was 40 (30–55 15–105) s. The Glidescope® provided a grade I view of the glottis in 44 cases and a grade II view in six cases. The view of the larynx was improved in almost half (23) of the cases. The Glidescope® improved the view by one grade in 22 and by two grades in one patient. We conclude that the Glidescope® is an effective device for tracheal intubation and provides an improved view of the larynx. Further clinical studies are necessary to evaluate its role in airways that are difficult to manage.
The study was focused on assessment of antibacterial activity, cytotoxicity and immune compatibility of biogenic silver nanoparticles (AgNPs) synthesized from
Streptomyces
sp. NH28 strain. ...Nanoparticles were biosynthesized and characterized by UV–Vis spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, nanoparticle tracking analysis system and zeta potential. Antibacterial activity was tested against Gram-positive and Gram-negative bacteria; minimal inhibitory concentration was recorded. Cytotoxicity was estimated using L929 mouse fibroblasts via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Biocompatibility of AgNPs was performed using THP1-XBlue™ cells. Biogenic AgNPs presented high antibacterial activity against all tested bacteria. Minimum inhibitory concentration of AgNPs against bacterial cells was found to be in range of 1.25–10 μg/mL. Silver nanoparticles did not show any harmful interaction to mouse fibroblast cell line, and no activation of nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) cells was observed at concentration below 10 µg/mL. The half-maximal inhibitory concentration (IC
50
) value was established at 64.5 μg/mL. Biological synthesis of silver can be used as an effective system for formation of metal nanoparticles. Biosynthesized AgNPs can be used as an antibacterial agent, which can be safe for eukaryotic cells.
Background. Miltefosine is the only oral drug available for treatment of Indian visceral leishmaniasis (VL), which was shown to have an efficacy of 94% in a phase III trial in the Indian ...subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India. Methods. An open-label, noncomparative study was performed in which 567 patients received oral miltefosine (50 mg for patients weighing <25 kg, 100 mg in divided doses for those weighing ≥25 kg, and 2.5 mg per kg for those aged <12 years, daily for 28 days) in a directly observed manner. Patients were followed up for 6 months to see the response to therapy. Results. At the end of treatment the initial cure rate was 97.5% (intention to treat), and 6 months after the end of treatment the final cure rate was 90.3%. The overall death rate was 0.9% (5 of 567), and 2 deaths were related to drug toxicity. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 patients (1.5%) because of drug-associated adverse events. Conclusions. As compared to the phase III trial that led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India.
A series of novel ether-linked bis(heterocycle)s have been synthesized via 3
+
2-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition ...reaction of nitrile imine with carbonyl group. All the newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Among the list of compounds (
7a–
k) studied,
7d,
7g,
7j, and
7k exhibited excellent activity comparable to ibuprofen and aspirin at the similar dosages.
A series of novel ether-linked bis(heterocycle)s have been synthesized via 3
+
2-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition reaction of nitrile imine with carbonyl group.
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Abstract
We describe the immunologic and virologic impact of monkeypox (mpox) infection in a woman with human immunodeficiency virus (HIV) whose plasma HIV viremia was suppressed by clinically ...effective antiretroviral therapy. Extensive phenotypic analyses of B and T cells in peripheral blood and biomarkers in plasma showed significant immunologic perturbations despite the presence of mild mpox disease. Dramatic shifts were noted in the frequencies of total B cells, plasmablasts, and plasmablast immunoglobulin isotypes. Flow cytometric analyses showed a dramatic increase in the frequency of CD38+HLA-DR+ CD8+ T cells after mpox infection. Our data offer guidance for future studies involving mpox infection in affected populations.
We describe the immunologic and virologic impact of monkeypox infection in a woman with human immunodeficiency virus receiving antiretroviral therapy. Extensive phenotypic analyses of B and T cells and biomarkers showed significant immunologic perturbations despite mild monkeypox infection.
To assess the impact of osteoarthritis (OA) on the meniscus by comparing transcripts and biological processes in the meniscus between patients with and without OA.
RNA microarrays were used to ...identify transcripts differentially expressed (DE) in meniscus obtained from 12 OA and 12 non-OA patients. The non-OA specimens were obtained at the time of arthroscopic partial meniscectomy. Real-time PCR was performed on selected transcripts. Biological processes and gene-networking was examined computationally. Transcriptome signatures were mapped with 37 OA-related transcripts to evaluate how meniscus gene expression relates to that of OA cartilage.
We identified 168 transcripts significantly DE between OA (75 elevated, 93 repressed) and non-OA samples (≥1.5-fold). Among these, CSN1S1, COL10A1, WIF1, and SPARCL1 were the most prominent transcripts elevated in OA meniscus, POSTN and VEGFA were most highly repressed in OA meniscus. Transcripts elevated in OA meniscus represented response to external stimuli, cell migration and cell localization while those repressed in OA meniscus represented histone deacetylase activity (related to epigenetics) and skeletal development. Numerous long non-coding RNAs (lncRNAs) were DE between the two groups. When segregated by OA-related transcripts, two distinct clustering patterns appeared: OA meniscus appeared to be more inflammatory while non-OA meniscus exhibited a “repair” phenotype.
Numerous transcripts with potential relevance to the pathogenesis of OA are DE in OA and non-OA meniscus. These data suggest an involvement of epigenetically regulated histone deacetylation in meniscus tears as well as expression of lncRNAs. Patient clustering based on transcripts related to OA in articular cartilage confirmed distinct phenotypes between injured (non-OA) and OA meniscus.
Biological systems such as bacteria, fungi or plants for synthesis of noble nanoparticles (NPs) are easy, inexpensive and eco-friendly. Obtained bioparticles due to its physico-chemical nature ...possess biologically active properties such as antimicrobial activity. In this study, the biological synthesis of silver (Ag) and gold (Au) nanoparticles using
Streptomyces
sp. strain NH21 isolated from acidic soil and its antibacterial activity against bacteria is presented. The physico-chemical properties of obtained particles were characterized. UV–Vis showed broad peak at 404 and 424 nm for AgNPs and 564 nm for AuNPs. Transmission electron microscopy studies showed small sized nanoparticles of 44 nm for supernatant and 8.4 nm for biomass synthesized AgNPs, and 10 nm for supernatant synthesized AuNPs, which was confirmed by nanoparticle tracking analyses. Fourier transform infrared spectroscopy revealed the presence of capping agents over metal-NPs. The negative Zeta potential values of metal-NPs indicated stability of biosynthesized particles.
In vitro
antibacterial activity and minimal inhibitory concentration of NPs was assessed against Gram-positive and Gram-negative bacteria. Unlike to gold-NPs, silver-NPs showed reliable antibacterial activity. Atomic force microscopy analysis recorded changes in cell morphology of tested bacterial strains after treatment with nanoparticles.
Anterior cruciate ligament (ACL) injury initiates a cascade of events often leading to osteoarthritis (OA). ACL reconstruction does not alter the course of OA, suggesting that heightened OA risk is ...likely due to factors in addition to the joint instability. We showed that torn ACL remnants express periostin (POSTN) in the acute phase of injury. Considering that ACL injury predisposes to OA and that POSTN is associated with cartilage metabolism, we hypothesize that ACL injury affects chondrocytes via POSTN.
Cartilage was obtained from osteoarthritic patients and ACL remnants were collected from patients undergoing ACL reconstruction. Crosstalk between ACL remnants and chondrocytes was studied in a transwell co-culture system. Expression of POSTN and other anabolic and catabolic genes was assessed via real-time polymerase chain reaction (PCR). Immunostaining for periostin was performed in human and mouse cartilage. The impact of exogenous periostin and siRNA-mediated ablation of periostin on matrix metabolism and cell migration was examined. Furthermore, the effect of anabolic (transforming growth factor beta 1 TGF-β1) and catabolic (interleukin 1 beta IL-1β) factors on POSTN expression was investigated.
ACL remnants induced expression of POSTN, MMP13 and ADAMTS4. Periostin levels were significantly higher in osteoarthritic compared to normal cartilage. Exogenous periostin induced MMP13 expression and cell migration, and repressed COL1A1 expression while POSTN knockdown inhibited expression of both anabolic and catabolic genes and impeded cell migration. TGF-β1 and IL-1β treatment did not alter POSTN expression but influenced chondrocyte metabolism as determined by quantification of anabolic and catabolic genes via real-time PCR.
ACL remnants can exert paracrine effects on cartilage, altering cellular homeostasis. Over time, this metabolic imbalance could contribute to OA development.
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