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1.
Cell ; 185(23): 4333-4346.e14, 2022 11 10.
Article in English | MEDLINE | ID: mdl-36257313

ABSTRACT

SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection.


Subject(s)
B-Lymphocytes , COVID-19 , Viral Vaccines , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , SARS-CoV-2 , Vaccination , B-Lymphocytes/immunology , mRNA Vaccines
2.
J Infect Dis ; 229(6): 1770-1780, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38128541

ABSTRACT

BACKGROUND: A better understanding of the dynamics of human immunodeficiency virus (HIV) reservoirs in CD4+ T cells of people with HIV (PWH) receiving antiretroviral therapy (ART) is crucial for developing therapies to eradicate the virus. METHODS: We conducted a study involving 28 aviremic PWH receiving ART with high and low levels of HIV DNA. We analyzed immunologic and virologic parameters and their association with the HIV reservoir size. RESULTS: The frequency of CD4+ T cells carrying HIV DNA was associated with higher pre-ART plasma viremia, lower pre-ART CD4+ T-cell counts, and lower pre-ART CD4/CD8 ratios. During ART, the High group maintained elevated levels of intact HIV proviral DNA, cell-associated HIV RNA, and inducible virion-associated HIV RNA. HIV sequence analysis showed no evidence for preferential accumulation of defective proviruses nor higher frequencies of clonal expansion in the High versus Low group. Phenotypic and functional T-cell analyses did not show enhanced immune-mediated virologic control in the Low versus High group. Of considerable interest, pre-ART innate immunity was significantly higher in the Low versus High group. CONCLUSIONS: Our data suggest that innate immunity at the time of ART initiation may play an important role in modulating the dynamics and persistence of viral reservoirs in PWH.


Subject(s)
CD4-Positive T-Lymphocytes , DNA, Viral , HIV Infections , Viral Load , Humans , HIV Infections/drug therapy , HIV Infections/virology , HIV Infections/immunology , Male , DNA, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , Female , Adult , Middle Aged , HIV-1/genetics , RNA, Viral/blood , Proviruses/genetics , Anti-Retroviral Agents/therapeutic use , CD4-CD8 Ratio , CD4 Lymphocyte Count , Viremia/drug therapy , Viremia/immunology , Viremia/virology , Anti-HIV Agents/therapeutic use
3.
J Infect Dis ; 228(3): 270-275, 2023 08 11.
Article in English | MEDLINE | ID: mdl-37022144

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.


Subject(s)
HIV Infections , HIV-1 , Mpox (monkeypox) , Female , Humans , Mpox (monkeypox)/drug therapy , Monkeypox virus , CD8-Positive T-Lymphocytes , HIV Infections/complications , HIV Infections/drug therapy
4.
J Appl Microbiol ; 131(4): 1652-1667, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33462841

ABSTRACT

Dematiaceous hyphomycetes (DH) are darkly pigmented fungi ubiquitously found all over the world as plant pathogens and saprophytes, and many of the members of this group have emerged as opportunistic pathogens. These fungi are responsible for a wide variety of infections including mycotic keratitis, which is considered as one of the major causes of corneal blindness, particularly in tropical and subtropical countries with an annual global burden of about 1 000 000 patients. The infection is more common in workers working in an outdoor environment. Moreover, trauma is found to be the most important predisposing cause of mycotic keratitis. Considerable delay in diagnosis and scarcity of effective pharmacological drugs are the major factors responsible for increased morbidity and visual impairment. Considering the crucial role of DH in mycotic keratitis, in the present review, we have focused on major DH with special emphasis on their pathogenicity, diagnosis and treatment strategies.


Subject(s)
Eye Infections, Fungal , Keratitis , Mitosporic Fungi , Cornea , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Fungi , Humans , Keratitis/diagnosis , Keratitis/drug therapy
5.
Osteoarthritis Cartilage ; 28(8): 1111-1120, 2020 08.
Article in English | MEDLINE | ID: mdl-32437968

ABSTRACT

OBJECTIVE: The etiology of osteoarthritis (OA) is unknown, however, there appears to be a significant contribution from genetics. We have identified recombinant inbred strains of mice derived from LG/J (large) and SM/J (small) strains that vary significantly in their ability to repair articular cartilage and susceptibility to post-traumatic OA due to their genetic composition. Here, we report cartilage repair phenotypes in the same strains of mice in which OA susceptibility was analyzed previously, and determine the genetic correlations between phenotypes. DESIGN: We used 12 recombinant inbred strains, including the parental strains, to test three phenotypes: ear-wound healing (n = 263), knee articular cartilage repair (n = 131), and post-traumatic OA (n = 53) induced by the surgical destabilization of the medial meniscus (DMM). Genetic correlations between various traits were calculated as Pearson's correlation coefficients of strain means. RESULTS: We found a significant positive correlation between ear-wound healing and articular cartilage regeneration (r = 0.71; P = 0.005). We observed a strong inverse correlation between articular cartilage regeneration and susceptibility to OA based on maximum (r = -0.54; P = 0.036) and summed Osteoarthritis Research Society International (OARSI) scores (r = -0.56; P = 0.028). Synovitis was not significantly correlated with articular cartilage regeneration but was significantly positively correlated with maximum (r = 0.63; P = 0.014) and summed (r = 0.70; P = 0.005) OARSI scores. Ectopic calcification was significantly positively correlated with articular cartilage regeneration (r = 0.59; P = 0.021). CONCLUSIONS: Using recombinant inbred strains, our study allows, for the first time, the measurement of genetic correlations of regeneration phenotypes with degeneration phenotypes, characteristic of OA (cartilage degeneration, synovitis). We demonstrate that OA is positively correlated with synovitis and inversely correlated with the ability to repair cartilage. These results suggest an addition to the risk paradigm for OA from a focus on degeneration to regeneration.


Subject(s)
Cartilage, Articular/injuries , Ear, External/injuries , Osteoarthritis, Knee/genetics , Regeneration/genetics , Wound Healing/genetics , Animals , Cartilage, Articular/physiology , Disease Models, Animal , Ear Cartilage/injuries , Ear Cartilage/physiology , Ear, External/physiology , Menisci, Tibial/surgery , Mice , Mice, Inbred Strains , Osteoarthritis, Knee/physiopathology , Phenotype , Regeneration/physiology , Wound Healing/physiology
6.
Osteoarthritis Cartilage ; 28(4): 516-527, 2020 04.
Article in English | MEDLINE | ID: mdl-31945456

ABSTRACT

OBJECTIVE: To investigate the transcriptomic differences in chondrocytes obtained from LG/J (large, healer) and SM/J (small, non-healer) murine strains in an attempt to discern the molecular pathways implicated in cartilage regeneration and susceptibility to osteoarthritis (OA). DESIGN: We performed RNA-sequencing on chondrocytes derived from LG/J (n = 16) and SM/J (n = 16) mice. We validated the expression of candidate genes and compared single nucleotide polymorphisms (SNPs) between the two mouse strains. We also examined gene expression of positional candidates for ear pinna regeneration and long bone length quantitative trait loci (QTLs) that display differences in cartilaginous expression. RESULTS: We observed a distinct genetic heterogeneity between cells derived from LG/J and SM/J mouse strains. We found that gene ontologies representing cell development, cartilage condensation, and regulation of cell differentiation were enriched in LG/J chondrocytes. In contrast, gene ontologies enriched in the SM/J chondrocytes were mainly related to inflammation and degeneration. Moreover, SNP analysis revealed that multiple validated genes vary in sequence between LG/J and SM/J in coding and highly conserved noncoding regions. Finally, we showed that most QTLs have 20-30% of their positional candidates displaying differential expression between the two mouse strains. CONCLUSIONS: While the enrichment of pathways related to cell differentiation, cartilage development and cartilage condensation infers superior healing potential of LG/J strain, the enrichment of pathways related to cytokine production, immune cell activation and inflammation entails greater susceptibility of SM/J strain to OA. These data provide novel insights into chondrocyte transcriptome and aid in identification of the quantitative trait genes and molecular differences underlying the phenotypic differences associated with individual QTLs.


Subject(s)
Cartilage/physiology , Chondrocytes/metabolism , Osteoarthritis/genetics , Regeneration/genetics , Animals , Carbonic Anhydrase II/genetics , Cartilage, Articular/physiology , Ear Auricle , Ear Cartilage/physiology , Gene Expression Profiling , Genetic Predisposition to Disease , Mice , Mice, Inbred Strains/genetics , Polymorphism, Single Nucleotide , Quantitative Trait Loci , RNA-Seq , Real-Time Polymerase Chain Reaction , Receptors, Tumor Necrosis Factor
7.
Osteoarthritis Cartilage ; 27(6): 945-955, 2019 06.
Article in English | MEDLINE | ID: mdl-30797944

ABSTRACT

OBJECTIVE: To compare the transcriptome of articular cartilage from knees with meniscus tears to knees with end-stage osteoarthritis (OA). DESIGN: Articular cartilage was collected from the non-weight bearing medial intercondylar notch of knees undergoing arthroscopic partial meniscectomy (APM; N = 10, 49.7 ± 10.8 years, 50% females) for isolated medial meniscus tears and knees undergoing total knee arthroplasty (TKA; N = 10, 66.0 ± 7.6 years, 70% females) due to end-stage OA. Ribonucleic acid (RNA) preparation was subjected to SurePrint G3 human 8 × 60K RNA microarrays to probe differentially expressed transcripts followed by computational exploration of underlying biological processes. Real-time polymerase chain reaction amplification was performed on selected transcripts to validate microarray data. RESULTS: We observed that 81 transcripts were significantly differentially expressed (45 elevated, 36 repressed) between APM and TKA samples (≥ 2 fold) at a false discovery rate of ≤ 0.05. Among these, CFD, CSN1S1, TSPAN11, CSF1R and CD14 were elevated in the TKA group, while CHI3L2, HILPDA, COL3A1, COL27A1 and FGF2 were highly expressed in APM group. A few long intergenic non-coding RNAs (lincRNAs), small nuclear RNAs (snoRNAs) and antisense RNAs were also differentially expressed between the two groups. Transcripts up-regulated in TKA cartilage were enriched for protein localization and activation, chemical stimulus, immune response, and toll-like receptor signaling pathway. Transcripts up-regulated in APM cartilage were enriched for mesenchymal cell apoptosis, epithelial morphogenesis, canonical glycolysis, extracellular matrix organization, cartilage development, and glucose catabolic process. CONCLUSIONS: This study suggests that APM and TKA cartilage express distinct sets of OA transcripts. The gene profile in cartilage from TKA knees represents an end-stage OA whereas in APM knees it is clearly earlier in the degenerative process.


Subject(s)
Cartilage, Articular/metabolism , Osteoarthritis, Knee/genetics , RNA/metabolism , Tibial Meniscus Injuries/genetics , Adult , Aged , Arthroplasty, Replacement, Knee , Case-Control Studies , Caseins/genetics , Chitinases/genetics , Collagen Type III/genetics , Complement Factor D/genetics , Female , Fibrillar Collagens/genetics , Fibroblast Growth Factor 2/genetics , Gene Expression Profiling , Humans , Lipopolysaccharide Receptors/genetics , Male , Meniscectomy , Middle Aged , Neoplasm Proteins/genetics , Osteoarthritis, Knee/surgery , Phenotype , RNA, Antisense/metabolism , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , RNA, Small Nuclear/metabolism , Real-Time Polymerase Chain Reaction , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Tetraspanins/genetics , Tibial Meniscus Injuries/surgery
8.
Osteoarthritis Cartilage ; 27(12): 1778-1789, 2019 12.
Article in English | MEDLINE | ID: mdl-31430535

ABSTRACT

OBJECTIVE: Emerging evidence suggests that injury to the anterior cruciate ligament (ACL) typically initiates biological changes that contribute to the development of osteoarthritis (OA). The molecular biomarkers or mediators of these biological events remain unknown. The goal of this exploratory study was to identify novel synovial fluid biomarkers associated with early biological changes following ACL injury distinct from findings in end-stage OA. METHODS: Synovial fluid was aspirated from patients with acute (≤30 days) and subacute (31-90 days) ACL tears and from patients with advanced OA and probed via tandem mass spectrometry for biomarkers to distinguish OA from ACL injury. Periostin (POSTN) was identified as a potential candidate. Further analyses of POSTN were performed in synovial fluid, OA cartilage, torn ACL remnants, and cultured cells and media by Western blot, PCR, immunostaining and ELISA. RESULTS: Synovial fluid analysis revealed that POSTN exhibited higher expression in subacute ACL injury than OA. POSTN expression was relatively low in cartilage/chondrocytes suggesting it is also produced by other intra-articular tissues. Conversely, high and time-dependent expression of POSTN in ACL tear remnants and isolated cells was consistent with the synovial fluid results. CONCLUSIONS: Elevated POSTN may provide a synovial fluid biomarker of subacute ACL injury setting separate from OA. Increased expression of POSTN in ACL suggests that the injured ACL may play a pivotal role in POSTN production, which is sensitive to time from injury. Previous studies have shown potential catabolic effects of POSTN, raising the possibility that POSTN contributes to the initiation of joint degeneration and may offer a window of opportunity to intervene in the early stages of post-traumatic OA.


Subject(s)
Anterior Cruciate Ligament Injuries/metabolism , Cell Adhesion Molecules/metabolism , Synovial Fluid/metabolism , Adolescent , Adult , Anterior Cruciate Ligament/metabolism , Anterior Cruciate Ligament Injuries/genetics , Blotting, Western , Cartilage, Articular/metabolism , Case-Control Studies , Cell Adhesion Molecules/genetics , Chondrocytes/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Middle Aged , Osteoarthritis, Knee/metabolism , Polymerase Chain Reaction , Proteomics , Tandem Mass Spectrometry , Young Adult
9.
Opt Express ; 27(5): 6459-6470, 2019 Mar 04.
Article in English | MEDLINE | ID: mdl-30876231

ABSTRACT

Structured light has been created by a myriad of near-and far-field techniques and has found both classical and quantum applications. In the case of orbital angular momentum (OAM), continuous spiral phase patterns in dynamic or geometric phase are often employed with the phase patterns existing across the entire transverse plane. Here, we exploit the uncertain relationship between OAM and angle in order to create structured OAM fields by using multilevel OAM holograms. We show theoretically and experimentally that only a multilevel angular phase contour in the near-field is needed to create structured OAM light in the far-field, exploiting the reciprocal nature of angular momentum and angle. We use this approach to demonstrate exotic 3D structured light control to show the Poynting vector's evolution in such fields and to highlight the physics underlying this phenomenon.

10.
Clin Radiol ; 74(12): 978.e15-978.e27, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31594559

ABSTRACT

Most soft-tissue lumps in the hand are benign, with ganglions being the commonest, but in the thenar region, solid soft-tissue masses are more common than a ganglion. In this review, we focus on soft-tissue lesions (neoplastic and non-neoplastic) presenting as a palpable lump in this region. A specific diagnosis can often be reached using ultrasonography and/or magnetic resonance imaging. Most of these lesions are managed in local hospitals or primary care, whereas some are referred to specialist centres. This review article will help both general and musculoskeletal radiologists to diagnose and characterise these lesions, provide a guide for further imaging, and provide an insight into imaging features that may need specific investigations such as core biopsy, tertiary referral, and further review at multidisciplinary meetings.


Subject(s)
Hand/diagnostic imaging , Diagnosis, Differential , Ganglion Cysts/diagnostic imaging , Humans , Magnetic Resonance Imaging , Soft Tissue Neoplasms/diagnostic imaging , Ultrasonography
11.
Osteoarthritis Cartilage ; 26(3): 422-432, 2018 03.
Article in English | MEDLINE | ID: mdl-29258882

ABSTRACT

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Gene Expression Profiling , Meniscus/metabolism , Osteoarthritis/metabolism , Aged , Case-Control Studies , Epigenesis, Genetic , Female , Gene Expression , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain Reaction , Transcriptome
12.
Osteoarthritis Cartilage ; 26(4): 588-599, 2018 04.
Article in English | MEDLINE | ID: mdl-29391276

ABSTRACT

OBJECTIVE: 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. DESIGN: 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-ß1]) and catabolic (interleukin 1 beta [IL-1ß]) factors on POSTN expression was investigated. RESULTS: 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-ß1 and IL-1ß treatment did not alter POSTN expression but influenced chondrocyte metabolism as determined by quantification of anabolic and catabolic genes via real-time PCR. CONCLUSIONS: ACL remnants can exert paracrine effects on cartilage, altering cellular homeostasis. Over time, this metabolic imbalance could contribute to OA development.


Subject(s)
Anterior Cruciate Ligament Injuries/complications , Cartilage, Articular/metabolism , Cell Adhesion Molecules/biosynthesis , Chondrocytes/metabolism , Osteoarthritis, Knee/etiology , Anterior Cruciate Ligament Injuries/metabolism , Anterior Cruciate Ligament Injuries/pathology , Cartilage, Articular/pathology , Cell Adhesion Molecules/genetics , Cells, Cultured , Chondrocytes/pathology , Gene Expression Regulation , Humans , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , RNA/genetics
13.
J Appl Microbiol ; 124(6): 1411-1424, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29427473

ABSTRACT

AIMS: Presently, the effective antimicrobial agents have been limited by the emergence of microbial strains with multidrug resistance and biofilm formation potential. In the present study, we report remarkable antimicrobial activity of silver nanoparticles (AgNPs) synthesized from Streptomyces calidiresistens IF11 and IF17 strains, including inhibition of biofilm formation and synergistic effect of AgNPs and antibiotics against selected bacteria and yeasts. Cytotoxic effect of AgNPs on mammalian cell lines was also evaluated. METHODS AND RESULTS: Analysis of biosynthesized AgNPs by Fourier Transform Infrared Spectroscopy and transmission electron microscopy revealed their spherical shape, small size in the range of 5-50 and 5-20 nm, respectively, as well as the presence of capping agents. Study of antimicrobial activity of AgNPs against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Candida albicans and Malassezia furfur evaluated by minimum inhibitory concentration (MIC) and minimum biocidal concentration (MBC) assays revealed that MICs of AgNPs from IF11 and IF17 strains against bacteria and yeasts were found to be in the range of 16-128 and 8-256 µg ml-1 , while MBCs were in the range of 48-192 and 32-256 µg ml-1 respectively. AgNPs inhibited biofilm formation of microbial strains, which was tested by using crystal violet stain. The highest synergistic effect determined by fractional inhibitory index of AgNPs with antibiotic (kanamycin or tetracycline) was found against Staph. aureus; while in case of yeasts, M. furfur showed highest sensitivity to AgNPs-ketoconazole combination (FIC = 0·12). The cytotoxic activity of AgNPs towards HeLa and 3T3 cell lines was studied by MTT assay. The IC50 of AgNPs estimated against mouse fibroblasts was found to be 8·3 and 28·3 µg ml-1 and, against HeLa cell line, 28·5 and 53·8 µg ml-1 respectively. CONCLUSIONS: It can be concluded that AgNPs synthesized from S. calidiresistens IF11 and IF17 strains have potential as an effective antimicrobial and cytotoxic agent, especially when used in combination with antibiotics/antifungal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates potential application of biogenic silver nanoparticles as an antimicrobial agent in nanomedicine.


Subject(s)
Anti-Infective Agents/metabolism , Silver/metabolism , Streptomyces/metabolism , 3T3 Cells , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Bacillus subtilis/drug effects , Candida albicans/drug effects , Cell Survival/drug effects , Escherichia coli/drug effects , HeLa Cells , Humans , Metal Nanoparticles/chemistry , Mice , Microbial Sensitivity Tests , Microscopy, Electron, Transmission , Silver/pharmacology , Sodium Chloride/metabolism , Staphylococcus aureus/drug effects
14.
Pak J Pharm Sci ; 30(5): 1557-1565, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29084673

ABSTRACT

Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.


Subject(s)
Antihypertensive Agents/chemistry , Atenolol/chemistry , Atorvastatin/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Administration, Oral , Antihypertensive Agents/administration & dosage , Atenolol/administration & dosage , Atorvastatin/administration & dosage , Calorimetry, Differential Scanning , Drug Combinations , Drug Compounding , Drug Liberation , Excipients/chemistry , Gelatin/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Kinetics , Rheology , Solubility , Spectroscopy, Fourier Transform Infrared , Starch/analogs & derivatives , Starch/chemistry , Sublimation, Chemical , Tablets , Technology, Pharmaceutical/methods
16.
Opt Lett ; 41(15): 3635-8, 2016 Aug 01.
Article in English | MEDLINE | ID: mdl-27472637

ABSTRACT

We have studied a wide-bandgap oxide semiconductor, CaGa1.99Cr0.01O4, which possesses high crystal field strength and develops deep traps. These traps efficiently store electric charges after excitation with ultraviolet light. Stimulation of trap charges using infrared radiation (both coherent and incoherent) gives wideband emission of Cr3+ in the red-infrared region, which is similar to the photon upconversion process in lanthanides. Under laser excitation, high photon density and local heating pronounce the coupling of E2 and T24 states and causes an excited state crossover of the population from the E2 to T24 state. This expands the emission band-width of Cr3+ up to 900 nm.

17.
Med Microbiol Immunol ; 205(6): 603-613, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27620485

ABSTRACT

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 (IC50) 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.


Subject(s)
Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Metal Nanoparticles , Silver/immunology , Silver/pharmacology , Animals , Anti-Bacterial Agents/toxicity , Cell Line , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Mice , Microbial Sensitivity Tests , Silver/toxicity , Spectroscopy, Fourier Transform Infrared
18.
J Appl Microbiol ; 120(3): 527-42, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26599354

ABSTRACT

With the rise in human population across the globe especially in developing countries, the incidence of microbial infections are increasing with greater pace. On the other hand, available medication and therapies are found to be insufficient for the complete cure of such microbial infections due to the development of resistance against various antibiotics. Therefore, to cope up the menace of microbial infections and drug resistance, there is demand for new and compelling technology, which has the ability to impede these problems. Many research groups worldwide are finding a ray of hope in nanomaterials owing to their unique properties. In the present review we have discussed the reasons behind the development of new materials based on nanotechnology. It is mainly focused on pioneering studies on application of nanomaterials like carbon nanotube, fullerene, dendrimers, nanocomposite and metal nanoparticles in combating dreadful pathogens. Moreover, the concerns about their toxicity have also been discussed.


Subject(s)
Bacterial Infections/drug therapy , Nanostructures/therapeutic use , Nanotechnology , Animals , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/microbiology , Humans , Nanostructures/toxicity
19.
Mycoses ; 59(3): 157-66, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26671603

ABSTRACT

Superficial mycoses are limited to the most external part of the skin and hair and caused by Malassezia sp., Trichophyton sp. and Candida sp. We report extracellular biosynthesis of silver nanoparticles (AgNPs) by acidophilic actinobacteria (SF23, C9) and its in vitro antifungal activity against fungi-causing superficial mycoses. The phylogenetic analysis based on the 16S rRNA gene sequence of strains SF23 and C9 showed that they are most closely related to Pilimelia columellifera subsp. pallida GU269552(T). The detection of AgNPs was confirmed by visual observation of colour changes from colourless to brown, and UV-vis spectrophotometer analysis, which showed peaks at 432 and 427 nm, respectively. These AgNPs were further characterised by nanoparticle tracking analysis (NTA), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The FTIR analysis exhibited the presence of proteins as capping agents. The TEM analysis revealed the formation of spherical and polydispersed nanoparticles in the size range of 4-36 nm and 8-60 nm, respectively. The biosynthesised AgNPs were screened against fungi-causing superficial mycoses viz., Malassezia furfur, Trichophyton rubrum, Candida albicans and C. tropicalis. The highest antifungal activity of AgNPs from SF23 and C9 against T. rubrum and the least against M. furfur and C. albicans was observed as compared to other tested fungi. The biosynthesised AgNPs were found to be potential anti-antifungal agent against fungi-causing superficial mycoses.


Subject(s)
Actinobacteria/metabolism , Antifungal Agents/therapeutic use , Dermatomycoses/drug therapy , Metal Nanoparticles/chemistry , Actinobacteria/classification , Actinobacteria/genetics , Algorithms , Antifungal Agents/pharmacology , Base Sequence , Candida albicans/drug effects , Candida tropicalis/drug effects , Dermatomycoses/microbiology , Drug Synergism , Humans , Ketoconazole/pharmacology , Ketoconazole/therapeutic use , Malassezia/drug effects , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/ultrastructure , Microbial Sensitivity Tests , Microscopy, Electron, Transmission , RNA, Ribosomal, 16S/genetics , Silver , Silver Nitrate/metabolism , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Trichophyton/drug effects
20.
Osteoarthritis Cartilage ; 23(3): 454-61, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25498590

ABSTRACT

OBJECTIVE: C-C chemokine receptor type 5 (CCR5) has been implicated in rheumatoid arthritis and several inflammatory diseases, where its blockade resulted in reduced joint destruction. However, its role in modulating cartilage and bone changes in post-traumatic osteoarthritis (OA) has not yet been investigated. In this study, we investigated changes in articular cartilage, synovium and bone in a post-traumatic OA model using CCR5-deficient (CCR5(-/-)) mice. METHOD: Destabilization of the medial meniscus (DMM) was performed on the right knee of 10-week old CCR5(-/-) and C57BL/6J wild-type (WT) mice to induce post-traumatic OA. The contralateral left knee served as sham-operated control. Knee joints were analyzed at 4-, 8- and 12-weeks after surgery to evaluate cartilage degeneration and synovitis by histology, and bone changes via micro-CT. RESULTS: Our findings showed that CCR5(-/-) mice exhibited significantly less cartilage degeneration than WT mice at 8- and 12-weeks post-surgery. CCR5(-/-) mice showed some altered bone parameters 18- and 22-weeks of age, but body size and weight were not affected. The effect of CCR5-ablation was insignificant at all time points post-surgery for synovitis and for bone parameters such as bone volume/total volume, connectivity density index (CDI), structure model index (SMI), subchondral bone plate thickness, and trabecular bone number, thickness and spacing. CONCLUSION: These findings suggest that CCR5(-/-) mice developed less cartilage degeneration, which may indicate a potential protective role of CCR5-ablation in cartilage homeostasis. There were no differences in bone or synovial response to surgery suggesting that CCR5 functions primarily in cartilage during the development of post-traumatic OA.


Subject(s)
Cartilage, Articular/pathology , Femur/diagnostic imaging , Osteoarthritis, Knee/genetics , Receptors, CCR5/genetics , Synovial Membrane/pathology , Tibia/diagnostic imaging , Tibial Meniscus Injuries , Animals , Disease Models, Animal , Femur/pathology , Knee Injuries/complications , Mice , Mice, Knockout , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/etiology , Tibia/pathology , X-Ray Microtomography
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