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1.
Arch Virol ; 169(7): 145, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864875

RESUMO

Since 2020, African swine fever (ASF) has affected all pig breeds in Northeast India except Doom pigs, a unique indigenous breed from Assam and the closest relatives of Indian wild pigs. ASF outbreaks result in significant economic losses for pig farmers in the region. Based on sequencing and phylogenetic analysis of the B646L (p72) gene, it has been determined that ASFV genotype II is responsible for outbreaks in this region. Recent studies have shown that MYD88, LDHB, and IFIT1, which are important genes of the immune system, are involved in the pathogenesis of ASFV. The differential expression patterns of these genes in surviving ASFV-infected and healthy Doom breed pigs were compared to healthy controls at different stages of infection. The ability of Doom pigs to withstand common pig diseases, along with their genetic resemblance to wild pigs, make them ideal candidates for studying tolerance to ASFV infection. In the present study, we investigated the natural resistance to ASF in Doom pigs from an endemic area in Northeast India. The results of this study provide important molecular insights into the regulation of ASFV tolerance genes.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Surtos de Doenças , Filogenia , Animais , Febre Suína Africana/virologia , Febre Suína Africana/epidemiologia , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/imunologia , Índia/epidemiologia , Suínos , Surtos de Doenças/veterinária , Genótipo , Fator 88 de Diferenciação Mieloide/genética , Resistência à Doença/genética
2.
Arch Virol ; 169(3): 54, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381218

RESUMO

African swine fever (ASF) has emerged as a threat to swine production worldwide. Evasion of host immunity by ASF virus (ASFV) is well understood. However, the role of ASFV in triggering oncogenesis is still unclear. In the present study, ASFV-infected kidney tissue samples were subjected to Illumina-based transcriptome analysis. A total of 2463 upregulated and 825 downregulated genes were differentially expressed (p < 0.05). A literature review revealed that the majority of the differentially expressed host genes were key molecules in signaling pathways involved in oncogenesis. Bioinformatic analysis indicated the activation of certain oncogenic KEGG pathways, including basal cell carcinoma, breast cancer, transcriptional deregulation in cancer, and hepatocellular carcinoma. Analysis of host-virus interactions revealed that the upregulated oncogenic RELA (p65 transcription factor) protein of Sus scrofa can interact with the A238L (hypothetical protein of unknown function) of ASFV. Differential expression of oncogenes was confirmed by qRT-PCR, using the H3 histone family 3A gene (H3F3A) as an internal control to confirm the RNA-Seq data. The levels of gene expression indicated by qRT-PCR matched closely to those determined through RNA-Seq. These findings open up new possibilities for investigation of the mechanisms underlying ASFV infection and offer insights into the dynamic interaction between viral infection and oncogenic processes. However, as these investigations were conducted on pigs that died from natural ASFV infection, the role of ASFV in oncogenesis still needs to be investigated in controlled experimental studies.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Neoplasias Hepáticas , Animais , Suínos , Vírus da Febre Suína Africana/genética , Transcriptoma , Febre Suína Africana/genética , Oncogenes , Transformação Celular Neoplásica , Carcinogênese/genética
3.
Proc Natl Acad Sci U S A ; 118(33)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34385327

RESUMO

Dirac fermions play a central role in the study of topological phases, for they can generate a variety of exotic states, such as Weyl semimetals and topological insulators. The control and manipulation of Dirac fermions constitute a fundamental step toward the realization of novel concepts of electronic devices and quantum computation. By means of Angle-Resolved Photo-Emission Spectroscopy (ARPES) experiments and ab initio simulations, here, we show that Dirac states can be effectively tuned by doping a transition metal sulfide, [Formula: see text], through Co/Ni substitution. The symmetry and chemical characteristics of this material, combined with the modification of the charge-transfer gap of [Formula: see text] across its phase diagram, lead to the formation of Dirac lines, whose position in k-space can be displaced along the [Formula: see text] symmetry direction and their form reshaped. Not only does the doping x tailor the location and shape of the Dirac bands, but it also controls the metal-insulator transition in the same compound, making [Formula: see text] a model system to functionalize Dirac materials by varying the strength of electron correlations.

4.
J Food Sci Technol ; 61(8): 1516-1524, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38966784

RESUMO

Escherichia coli and Staphylococcus aureus are the most important food borne pathogen transmitting from animal meat and meat products. Therefore, it is vital to design an accurate and specific diagnostic tool for identifying those food-borne pathogens in animal meat and meat products. In the current study, E. coli, methicillin-resistant and sensitive S. aureus (MRSA and MSSA) were simultaneously detected using a developed triplex PCR-based technique. To obtain an optimal reaction parameter, the multiplex assay was optimised by changing just one parameter while holding the others constant. Specificity of the assay was assessed using several porcine bacterial template DNA. The plasmid DNA was used to test the multiplex PCR assay's sensitivity and interference in spiked pork samples. E. coli, MRSA, and MSSA each have PCR amplified products with sizes of 335, 533, and 209 bp, respectively. The assay detects a minimum microbial load of 102 CFU/µl for all the three pathogens and can identify bacterial DNA as low as 10-2 ng/µl. The assay was validated employing 210 pork samples obtained from retail meat shops and slaughter houses, with MRSA, E. coli, and MSSA with the occurrence rate of 1.9%, 42.38%, and 18.1%, respectively. The rate of mixed bacterial contamination in pork meat samples examined with the developed method was 6.19%, 1.43%, 1.90%, and 1.43% for MSSA & E. coli, MRSA & E. coli, MSSA & MRSA, and E. coli, MSSA & MRSA, respectively. The developed multiplex PCR assay is quick and efficient, and it can distinguish between different bacterial pathogens in a single reaction tube.

5.
Microb Pathog ; 185: 106452, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37972743

RESUMO

The present investigation focuses on examining the clinical, histopathological, and ultrastructural changes that occurred in pig, during an outbreak of African swine fever (ASF) in 2022 in Assam, India. The disease initially manifested as a per-acute case with high mortality but without any evident clinical signs. Subsequently, some animals exhibited an acute form of the disease characterized by high fever (104-106 °F), anorexia, vomiting, respiratory distress, and bleeding from the anal and nasal orifices. During acute African swine fever virus (ASFV) infections, elevated levels of pro-inflammatory IL-1α, IL-1ß, IL-6, TNF, CCL2, CCL5, and CXCL10 were detected in the palatine tonsil, lymph nodes, spleen, and kidney using qPCR assay. These molecular changes were associated with haemorrhages, edemas, and lymphoid depletion. Postmortem examinations revealed prominent features such as splenomegaly with haemorrhages, haemorrhagic lymphadenitis, severe petechial haemorrhage in the kidney, pneumonia in the lungs, and necrotic palatine tonsil. Histopathological analysis demonstrated lymphocyte depletion in lymphoid organs, multi-organ haemorrhages, and interstitial pneumonia in the lungs. Scanning electron microscopy (SEM) further confirmed lymphocyte depletion in lymphoid organs through lymphocyte apoptosis and kidney damage with distorted tubules due to red blood cell destruction. Transmission electron microscopy reaffirmed lymphocyte apoptosis by observing chromatin condensation and nucleus margination in lymphocytes of lymphoid organs. These findings provide comprehensive insights into the clinical, histopathological, and ultrastructural aspects of ASF outbreak in pigs. Understanding the pathological changes associated with ASF can contribute to improved diagnosis, prevention, and control measures for this highly contagious and economically devastating viral disease.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Febre Suína Africana/epidemiologia , Febre Suína Africana/patologia , Linfócitos , Surtos de Doenças , Hemorragia , Sus scrofa
6.
Anim Biotechnol ; 34(6): 1883-1890, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35343866

RESUMO

A diagnostic method for simultaneously detecting and distinguishing African Swine Fever (ASF), porcine circovirus type 2 (PCV2), and porcine parvovirus (PPV) in clinical specimens is critical for differential diagnosis, monitoring, and control in the field. Three primer pairs were designed and used to create a multiplex PCR assay. In addition, 356 porcine post mortem tissue samples from various parts of India's North Eastern region were tested by the developed multiplex PCR assay to demonstrate its accuracy. Using the designed primers, each of the ASF, PCV2 and PPV target genes was amplified, but no other porcine virus genes were detected. The assay's limit of detection was 102 copies/µl of PCV2, PPV, or ASFV. The detection of PCV2, PPV, and ASF in postmortem tissue samples revealed that they are co-circulating in India's North-Eastern region. The percentage positivity (PP) for PCV2, PPV and ASF single infection were 7.02% (25/356), 3.93% (14/356), and 3.37% (12/356), respectively, while the PP for PCV2& PPV co-infection was 2.80% (10/356), ASF & PCV2 co infection was 1.4% (5/356) and the ASF, PPV& PCV2 co-infection was1.40% (5/356). The results also indicate that the ASF can infect pigs alongside PCV and PPV.


Assuntos
Febre Suína Africana , Infecções por Circoviridae , Coinfecção , Infecções por Parvoviridae , Parvovirus Suíno , Doenças dos Suínos , Viroses , Animais , Suínos , Reação em Cadeia da Polimerase Multiplex/veterinária , Reação em Cadeia da Polimerase Multiplex/métodos , Febre Suína Africana/diagnóstico , Coinfecção/diagnóstico , Coinfecção/veterinária , Infecções por Circoviridae/diagnóstico , Infecções por Circoviridae/veterinária , Doenças dos Suínos/diagnóstico , Viroses/diagnóstico , Parvovirus Suíno/genética
7.
Mem Inst Oswaldo Cruz ; 117: e220014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35703715

RESUMO

BACKGROUND: Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation. OBJECTIVES: To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects. METHODS: The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. RESULTS: The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-ß1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test. CONCLUSION: These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.


Assuntos
Hanseníase Paucibacilar , Hanseníase , Brasil , Moléculas de Adesão Celular , Humanos , Lectinas Tipo C , Hanseníase/genética , Hanseníase Paucibacilar/genética , Mycobacterium leprae/genética , Receptores de Superfície Celular
8.
Nano Lett ; 21(18): 7448-7456, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34498884

RESUMO

A concept of spin plasmon, a collective mode of spin-density, in strongly correlated electron systems has been proposed since the 1930s. It is expected to bridge between spintronics and plasmonics by strongly confining the photon energy in the subwavelength scale within single magnetic-domain to enable further miniaturizing devices. However, spin plasmon in strongly correlated electron systems is yet to be realized. Herein, we present a new spin correlated-plasmon at room temperature in novel Mott-like insulating highly oriented single-crystalline gold quantum-dots (HOSG-QDs). Interestingly, the spin correlated-plasmon is tunable from the infrared to visible, accompanied by spectral weight transfer yielding a large quantum absorption midgap state, disappearance of low-energy Drude response, and transparency. Supported with theoretical calculations, it occurs due to an interplay of surprisingly strong electron-electron correlations, s-p hybridization and quantum confinement in the s band. The first demonstration of the high sensitivity of spin correlated-plasmon in surface-enhanced Raman spectroscopy is also presented.

9.
Opt Express ; 28(9): 12922-12935, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32403778

RESUMO

Undesired mask-induced effects caused by thick absorber layers in EUV photomasks reduce the quality of the projected patterns at the wafer stage in EUV photolithography scanners. New materials with better absorption properties than the state-of-the-art absorbers, TaN and TaBN, are required to mitigate these effects. In this work, we investigated the optical properties (δ and k) of Te and TeO films in the 13-14 nm range, and the absorption properties of these two materials at 13.5 nm. δ and k are obtained through fitting experimental values of reflectivity versus angle of incidence in the EUV range. We follow a methodology which combines different characterization techniques (X-ray reflectivity, EUV reflectivity, and X-ray photoemission spectroscopy) to reduce the number of free parameters in models and hence, increase the reliability of the optical constants obtained. At 13.5 nm, we obtain δ=0.03120, k = 0.07338 for Te, and δ=0.04099, k = 0.06555 for TeO. To experimentally verify the absorption properties of these materials, different thicknesses of Te and TeO films are cast on top of a state-of-the-art mask-quality EUV multilayer with 66.7% reflectivity at 13.5 nm. We found that a reflectivity of ∼0.7% can be attained with either 32.4 nm of Te, or 34.7 nm of TeO, greatly surpassing the absorption properties of TaN and TaBN. The morphology and surface roughness of the Te and TeO films deposited on the multilayer are also investigated.

10.
Curr Cardiol Rep ; 22(6): 42, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430629

RESUMO

PURPOSE OF REVIEW: Shorter hospital stay after percutaneous coronary intervention (PCI) can provide economic advantage. Same-day discharge (SDD) after transradial PCI is thought to reduce the cost of care while maintaining the quality and safety. This review summarizes the current knowledge of the benefits and safety of this concept. RECENT FINDINGS: Increase in rate of transradial PCI over the last two decades has resulted in recent growth in rate of acceptance of SDD after a successful procedure. SDD is shown to result in savings of $3500 to $5200 per procedure with comparable adverse event rate of traditional discharge processes. SDD after PCI is shown to be safe and results in cost advantage maintaining the safety profile. The acceptance rate of SDD is still not optimum, and further market penetration of SDD practice would be achieved only if the institutional and operator preference barriers are addressed.


Assuntos
Assistência Ambulatorial/economia , Procedimentos Cirúrgicos Eletivos/economia , Alta do Paciente/economia , Intervenção Coronária Percutânea/economia , Redução de Custos , Análise Custo-Benefício , Humanos , Tempo de Internação/economia , Alta do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/estatística & dados numéricos , Artéria Radial , Stents , Fatores de Tempo , Resultado do Tratamento
11.
Indian J Public Health ; 64(4): 398-401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33318392

RESUMO

Retinopathy of prematurity (ROP), particularly severe ROP is a health concern. The study is aimed to ascertain the magnitude, profile, and outcome of ROP over 5 years at a level II neonatal unit in a district of West Bengal. From 2012 to 2016, a total of 691 newborns with birth weight (BW) <2000 g and/or gestational age < 35 weeks of a district level II neonatal care unit were screened for ROP. Retrospective analysis of these screened babies was performed using the principles of descriptive and inferential statistics. Overall, 38.5% of newborns had any stage ROP and13.2% severe ROP. Two-thirds of babies with severe ROP were <1250 g of BW. About 16.2% of the ROP cases suffered from aggressive posterior ROP (APROP). Oxygen and prematurity were found as significant risk factors. Substantially high occurrence of severe ROP and APROP warrants appropriate measures. Timely screening and intervention with referral to the neonatal ROP unit can improve the scenario.


Assuntos
Retinopatia da Prematuridade , Idade Gestacional , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Retinopatia da Prematuridade/epidemiologia , Estudos Retrospectivos
12.
J Synchrotron Radiat ; 24(Pt 4): 750-756, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28664881

RESUMO

Complete photoemission experiments, enabling measurement of the full quantum set of the photoelectron final state, are in high demand for studying materials and nanostructures whose properties are determined by strong electron and spin correlations. Here the implementation of the new spin polarimeter VESPA (Very Efficient Spin Polarization Analysis) at the APE-NFFA beamline at Elettra is reported, which is based on the exchange coupling between the photoelectron spin and a ferromagnetic surface in a reflectometry setup. The system was designed to be integrated with a dedicated Scienta-Omicron DA30 electron energy analyzer allowing for two simultaneous reflectometry measurements, along perpendicular axes, that, after magnetization switching of the two targets, allow the three-dimensional vectorial reconstruction of the spin polarization to be performed while operating the DA30 in high-resolution mode. VESPA represents the very first installation for spin-resolved ARPES (SPARPES) at the Elettra synchrotron in Trieste, and is being heavily exploited by SPARPES users since autumn 2015.

13.
Phys Rev Lett ; 119(2): 026403, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28753342

RESUMO

By combining bulk sensitive soft-x-ray angular-resolved photoemission spectroscopy and first-principles calculations we explored the bulk electron states of WTe_{2}, a candidate type-II Weyl semimetal featuring a large nonsaturating magnetoresistance. Despite the layered geometry suggesting a two-dimensional electronic structure, we directly observe a three-dimensional electronic dispersion. We report a band dispersion in the reciprocal direction perpendicular to the layers, implying that electrons can also travel coherently when crossing from one layer to the other. The measured Fermi surface is characterized by two well-separated electron and hole pockets at either side of the Γ point, differently from previous more surface sensitive angle-resolved photoemission spectroscopy experiments that additionally found a pronounced quasiparticle weight at the zone center. Moreover, we observe a significant sensitivity of the bulk electronic structure of WTe_{2} around the Fermi level to electronic correlations and renormalizations due to self-energy effects, previously neglected in first-principles descriptions.

14.
PLoS Genet ; 10(10): e1004712, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25340504

RESUMO

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.


Assuntos
20-Hidroxiesteroide Desidrogenases/genética , Variações do Número de Cópias de DNA/genética , Genoma , Cavalos/genética , Animais , Sequência de Bases , Cruzamento , Hibridização Genômica Comparativa , Humanos
16.
Nano Lett ; 16(6): 3409-14, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27010705

RESUMO

Topological insulators are a promising class of materials for applications in the field of spintronics. New perspectives in this field can arise from interfacing metal-organic molecules with the topological insulator spin-momentum locked surface states, which can be perturbed enhancing or suppressing spintronics-relevant properties such as spin coherence. Here we show results from an angle-resolved photemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM) study of the prototypical cobalt phthalocyanine (CoPc)/Bi2Se3 interface. We demonstrate that that the hybrid interface can act on the topological protection of the surface and bury the Dirac cone below the first quintuple layer.

17.
Drug Dev Ind Pharm ; 42(9): 1482-94, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26850463

RESUMO

CONTEXT: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach. OBJECTIVE: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma. METHODS: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study. RESULTS: The particle size distribution was found to be in the range of 78.82-587.8 nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer. CONCLUSION: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.


Assuntos
Antineoplásicos/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Resinas Acrílicas/química , Administração Cutânea , Animais , Antineoplásicos/química , Química Farmacêutica/métodos , Portadores de Fármacos/química , Estabilidade de Medicamentos , Feminino , Géis/administração & dosagem , Géis/química , Lipídeos/química , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Paclitaxel/química , Tamanho da Partícula , Permeabilidade , Absorção Cutânea/fisiologia
18.
Acta Neuropathol ; 129(5): 653-67, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25772973

RESUMO

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Complexo de Ataque à Membrana do Sistema Complemento/toxicidade , Hanseníase/patologia , Lipopolissacarídeos/toxicidade , Mycobacterium leprae/patogenicidade , Traumatismos do Sistema Nervoso/microbiologia , Animais , Animais não Endogâmicos , Axônios/efeitos dos fármacos , Axônios/microbiologia , Axônios/patologia , Biópsia , Ativação do Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Feminino , Humanos , Hanseníase/metabolismo , Hanseníase/microbiologia , Camundongos , Mycobacterium leprae/química , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/microbiologia , Bainha de Mielina/patologia , Traumatismos do Sistema Nervoso/imunologia , Traumatismos do Sistema Nervoso/patologia
19.
Mol Pharm ; 12(8): 2651-64, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-25941882

RESUMO

Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design, development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labeling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC-MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Pneumopatias Fúngicas/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Voriconazol/administração & dosagem , Voriconazol/farmacocinética , Administração por Inalação , Animais , Disponibilidade Biológica , Portadores de Fármacos , Feminino , Meia-Vida , Pneumopatias Fúngicas/metabolismo , Masculino , Camundongos , Nanopartículas/química , Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley
20.
Lepr Rev ; 86(1): 21-36, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26065145

RESUMO

OBJECTIVES: To explore the patient experience of being diagnosed with leprosy and the support provided during this process in selected populations in Brazil. To understand the information needs of patients during diagnosis. To identify characteristics of patients with different diagnostic experiences. To add to the evidence base used for improving the diagnostic process for leprosy patients. DESIGN: A self-constructed questionnaire delivered to 116 participants, at three leprosy health centres, across three states in Brazil. RESULTS: Most participants felt under-informed during diagnosis; 68.1% wanted more information about leprosy. Nearly one-quarter of patients reported feeling unable to ask questions at diagnosis. Almost half of patients reported being worried about treatment, yet 43.3% reported not having the chance to talk about their concerns. Younger participants were significantly more likely to report feeling unable to ask questions and talk about their worries. The majority of participants (59.5%) reported not being given any written information to take away with them. 36.5% reported not being given advice about how to reduce the chance of other family members becoming ill with leprosy. Older males were most likely to be given this advice despite females being in most contact with family members in most cultures. CONCLUSIONS: It is recommended that patients are encouraged to ask questions and invited to talk about their concerns, particularly younger patients. It is recommended that a simple information leaflet be provided to all patients. These suggestions may require some financial input, more staff and longer consultations but should significantly improve the diagnostic process.


Assuntos
Hanseníase/diagnóstico , Hanseníase/psicologia , Pacientes/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Conhecimento , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
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