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1.
Oral Oncol ; 125: 105697, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34999417

RESUMO

AIMS AND OBJECTIVES: To describe an inferior extension of a naso-labial flap as an adjunct to a maleo-labial flap in reconstruction of complete thickness defects around the oral commissure in 2 cases that we performed at our institute. METHODS: Two elderly cases of carcinoma buccal mucosa who underwent wide local excision along with neck dissection had moderately large peri-oral defects that are large to cover with nasolabial flap alone. An inferior extension to the maleo-labial flap was added, making it a naso-mento-labial flap to reconstruct the defects with an acceptable outcome aesthetically and functionally. The reconstructed defects' size was around 7 × 7cms and 8.5 × 6cms full-thickness defect in the buccal mucosa, respectively, with the extension of the defect in both the patients being almost the same with anterior extension to commissure, posteriorly to retro-molar trigone (RMT), laterally full-thickness, medially not involving alveolus. RESULTS: The incision at the donor site was closed primarily. The reconstruction did achieve the patient acceptable aesthetics, functionality, color and texture. The mean follow up of the patients is around 1 year with no complications. CONCLUSION: Naso-mento-labial flap, an inferiorly extended inferiorly based nasolabial flap is a useful addition to surgeon's armamentarium for reconstructing the buccal mucosa and peri-oral defects in patients whose general health prevents the using pedicled or free flaps.


Assuntos
Retalhos de Tecido Biológico , Procedimentos Cirúrgicos Reconstrutivos , Idoso , Retalhos de Tecido Biológico/cirurgia , Humanos , Mucosa Bucal/cirurgia , Esvaziamento Cervical , Nariz
2.
Front Immunol ; 12: 738431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707609

RESUMO

Mycoplasma genitalium and M. pneumoniae are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood. To gain insights on this, we infected HeLa cells independently with M. genitalium and M. pneumoniae and assessed gene expression by whole transcriptome sequencing (RNA-seq) approach. The results revealed that HeLa cells respond to M. genitalium and M. pneumoniae differently by regulating various protein-coding genes. Though there is a significant overlap between the genes regulated by these species, many of the differentially expressed genes were specific to each species. KEGG pathway and signaling network analyses revealed that the genes specific to M. genitalium are more related to cellular processes. In contrast, the genes specific to M. pneumoniae infection are correlated with immune response and inflammation, possibly suggesting that M. pneumoniae has some inherent ability to modulate host immune pathways.


Assuntos
Células Epiteliais/microbiologia , Mycoplasma genitalium/patogenicidade , Mycoplasma pneumoniae/patogenicidade , Transcriptoma , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Mycoplasma genitalium/imunologia , Mycoplasma pneumoniae/imunologia , Mapas de Interação de Proteínas , RNA-Seq , Transdução de Sinais , Sequenciamento Completo do Exoma
3.
Arch Microbiol ; 203(1): 137-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32783067

RESUMO

Advanced combinatorial treatments of surgery, chemotherapy, and radiotherapy do not have any effect on the enhancement of a 5-year survival rate of oral squamous cell carcinoma (OSCC). The discovery of early diagnostic non-invasive biomarkers is required to improve the survival rate of OSCC patients. Recently, it has been reported that oral microbiome has a significant contribution to the development of OSCC. Oral microbiome induces inflammatory response through the production of cytokines and chemokines that enhances tumor cell proliferation and survival. The study aims to develop saliva-based oral microbiome and cytokine biomarker panel that screen OSCC patients based on the level of the microbiome and cytokine differences. We compared the oral microbiome signatures and cytokine level in the saliva of OSCC patients and healthy individuals by 16S rRNA gene sequencing targeting the V3/V4 region using the MiSeq platform and cytokine assay, respectively. The higher abundance of Prevotella melaninogenica, Fusobacterium sp., Veillonella parvula, Porphyromonas endodontalis, Prevotella pallens, Dialister, Streptococcus anginosus, Prevotella nigrescens, Campylobacter ureolyticus, Prevotella nanceiensis, Peptostreptococcus anaerobius and significant elevation of IL-8, IL-6, TNF-α, GM-CSF, and IFN-γ in the saliva of patients having OSCC. Oncobacteria such as S. anginosus, V. parvula, P. endodontalis, and P. anaerobius may contribute to the development of OSCC by increasing inflammation via increased expression of inflammatory cytokines such as IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF. These oncobacteria and cytokines panels could potentially be used as a non-invasive biomarker in clinical practice for more efficient screening and early detection of OSCC patients.


Assuntos
Fenômenos Fisiológicos Bacterianos/imunologia , Citocinas/genética , Disbiose/complicações , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias Bucais/microbiologia , Saliva/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/imunologia , Citocinas/imunologia , Disbiose/imunologia , Disbiose/microbiologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Inflamação/microbiologia , Masculino , Microbiota/imunologia , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , RNA Ribossômico 16S/genética , Saliva/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia
4.
Ecancermedicalscience ; 15: 1318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047069

RESUMO

BACKGROUND: Oral mucositis related pain during CTRT in head and neck cancers is a common problem. Unfortunately, in spite of it being common, there is limited evidence for selection of systemic analgesic in this situation. Hence, this study was designed to compare the analgesic effect of a non-steroidal anti-inflammatory drug (diclofenac) versus a weak opioid (tramadol). PATIENTS AND METHODS: This was an open-label, parallel design, superiority randomised controlled study. In this study, head and neck cancer patients undergoing radical or adjuvant chemoradiation, who had grade 1 or above mucositis (in accordance with Common Terminology Criteria for Adverse Events version 4.03) and had pain related to it were randomly assigned to either diclofenac or tramadol for mucositis related pain control. The primary endpoint was analgesia after the first dose. The secondary endpoints were the rate of change in analgesic within 1 week, adverse events and quality of life. RESULTS: One hundred and twenty-eight patients were randomised, 66 in diclofenac and 62 in tramadol arm. The median area under the curve for graph of pain across time after first dose of pain medication for the diclofenac arm and the tramadol arm was 348.936 units (range: 113.64-1,969.23) and 420.87 (101.97-1,465.96), respectively, (p = 0.05619). Five patients (8.1%) in the tramadol arm and 11 patients (16.7%) in the diclofenac arm required a change in analgesic within 1 week of starting the analgesic (p = 0.184). There was no statistically significant difference in any adverse events between the two arms. However, the rate of any grade of renal dysfunction was numerically higher in the diclofenac arm (10.6% versus 4.8%, p = 0.326). CONCLUSION: In this phase 3 study, evaluating diclofenac and tramadol for chemoradiation induced mucositis pain, there was no statistical difference in analgesic activity of these two drugs.

5.
J Bacteriol ; 202(23)2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32928928

RESUMO

Here, we investigate the mycobacterial response to the combined stress of an organic oxidant (cumene hydroperoxide [CHP]) and a solvent (ethanol). To understand the interaction between the two stressors, we treated Mycobacterium smegmatis cells to a range of ethanol concentrations (2.5% to 10% [vol/vol]) in combination with a subinhibitory concentration of 1 mM CHP. It was observed that the presence of CHP increases the efficacy of ethanol in inducing rapid cell death. The data further suggest that ethanol reacts with the alkoxy radicals to produce ethanol-derived peroxides. These radicals induce significant membrane damage and lead to cell lysis. The ethanol-derived radicals were primarily recognized by the cells as organic radicals, as was evident by the differential upregulation of the ohr-ohrR genes that function in cells treated with the combination of ethanol and CHP. The role of organic peroxide reductase, Ohr, was further confirmed by the significantly higher sensitivity of the deletion mutant to CHP and the combined stress treatment of CHP and ethanol. Moreover, we also observed the sigma factor σB to be important for the cells treated with ethanol alone as well as the aforementioned combination. A ΔsigB mutant strain had significantly higher susceptibility to the stress conditions. This finding was correlated with the σB-dependent transcriptional regulation of ohr and ohrR In summary, our data indicate that the combination of low levels of ethanol and organic peroxides induce ethanol-derived organic radicals that lead to significant oxidative stress on the cells in a concentration-dependent manner.IMPORTANCE Bacterial response to a combination of stresses can be unexpected and very different compared with that of an individual stress treatment. This study explores the physiological and transcriptional response of mycobacteria in response to the combinatorial treatment of an oxidant with the commonly used solvent ethanol. The presence of a subinhibitory concentration of organic peroxide increases the effectiveness of ethanol by inducing reactive peroxides that destroy the membrane integrity of cells in a significantly short time span. Our work elucidates a mechanism of targeting the complex mycobacterial membrane, which is its primary source of intrinsic resistance. Furthermore, it also demonstrates the importance of exploring the effect of various stress conditions on inducing bacterial clearance.


Assuntos
Etanol/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Derivados de Benzeno/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Oxidantes/farmacologia
6.
Free Radic Biol Med ; 152: 323-335, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32222467

RESUMO

Methionine sulfoxide reductase A (MsrA) is a ubiquitous antioxidant repair enzyme which specifically reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Previous studies have shown that lack of or overexpression of MsrA in cells affects the function of proteins and can lead to altered cellular processes. Interestingly, some pathogenic bacteria secrete and/or carry MsrA on their surface, suggesting some key roles for this enzyme in the modulation of host cellular processes. Therefore, we investigated how exogenously added MsrA affects the ability of the host cells in combating infection by using an in vitroMycoplasma genitalium cytotoxicity model. HeLa cells pretreated with MsrA and infected with M. genitalium showed significantly lower necrosis (cytotoxicity) than untreated cells infected with M. genitalium. Intriguingly, necrotic cell death pathway specific real time RT-PCR revealed that M. genitalium infection upregulates the expression of the TNF gene in HeLa cells and that MsrA pretreatment of the cells downregulates its expression significantly. Consistent with this, enzyme linked immunosorbent assay (ELISA) results showed that HeLa cells pretreated with MsrA secreted reduced levels of TNF-α following M. genitalium infection. Also, our study demonstrates that MsrA treatment of cells affects the phosphorylation status of transcriptional regulators such as NF-кB, JNK and p53 that regulate different cytokines. Further, fluorescent microscopy showed the cellular uptake of exogenously added MsrA fused with red fluorescent protein (MsrA-RFP). Altogether, our results suggest that secreted MsrA may help pathogens to modulate host cellular processes.


Assuntos
Metionina Sulfóxido Redutases , Mycoplasma genitalium , Células HeLa , Humanos , Metionina , Metionina Sulfóxido Redutases/genética , Mycoplasma genitalium/genética , Fator de Necrose Tumoral alfa/genética
7.
Indian J Otolaryngol Head Neck Surg ; 71(4): 470-473, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31750105

RESUMO

Tracheostomy is a life-saving procedure done electively or most commonly in emergency basis. In patients with diagnosed case of cancer in upper airway tract they usually require tracheostomy at some point of time during their whole treatment procedure. Patients receiving radiotherapy or chemotherapy or combination of these are at high risk of developing post treatment changes in neck anatomy. Redo tracheostomy due to any reasons in such types of patients is a surgical challenge. The purpose of this article is to share our surgical technique in redo tracheostomy. During a period of two years 39 patients with diagnosed cancer in head neck region underwent redo tracheostomy at the hand of the author. Twenty-six patients were had received chemoradiation for their primary cancer and 6 patients were planned for second surgery due to recurrence disease in oral cavity. Reasons for redo tracheostomy are: sixteen patients were post chemoradiation on follow up with accidental expulsion of tube, 17 patients were recurrence/residual disease and 6 patients were plan for second surgery due to recurrence disease. In 9 cases the surgery was started by other doctor and taken over by the author due to profuse bleeding (5 cases) and failure to localised the trachea (4 cases). Among the 39 patients successful redo tracheostomy was possible in all. Mild surgical emphysema was encountered in 3 patients which was not significant. There was no other complication related to tracheostomy till the patients were discharge from the hospital. When redo tracheostomy is required in a post chemoradiation patients maintaining the proper dissection plane and procedure is important to avoid unnecessary complication intraoperatively.

8.
NPJ Vaccines ; 4: 34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396406

RESUMO

Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis due to M. tuberculosis (Mtb), which kills millions of people each year. BCG variably protects children, but not adults against tuberculosis. BCG evades phagosome maturation, autophagy, and reduces MHC-II expression of antigen-presenting cells (APCs) affecting T-cell activation. To bypass these defects, an autophagy-inducing, TLR-2 activating C5 peptide from Mtb-derived CFP-10 protein was overexpressed in BCG in combination with Ag85B. Recombinant BCG85C5 induced a robust MHC-II-dependent antigen presentation to CD4 T cells in vitro, and elicited stronger TH1 cytokines (IL-12, IL-1ß, and TNFα) from APCs of C57Bl/6 mice increasing phosphorylation of p38MAPK and ERK. BCG85C5 also enhanced MHC-II surface expression of MΦs by inhibiting MARCH1 ubiquitin ligase that degrades MHC-II. BCG85C5 infected APCs from MyD88 or TLR-2 knockout mice showed decreased antigen presentation. Furthermore, BCG85C5 induced LC3-dependent autophagy in macrophages increasing antigen presentation. Consistent with in vitro effects, BCG85C5 markedly expanded both effector and central memory T cells in C57Bl/6 mice protecting them against both primary aerosol infection with Mtb and reinfection, but was less effective among TLR-2 knockout mice. Thus, BCG85C5 induces stronger and longer lasting immunity, and is better than BCG against tuberculosis of mice.

9.
Natl J Maxillofac Surg ; 10(1): 8-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205382

RESUMO

Background: The purpose of this study was to determine the prevalence of Level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs). Materials and Methods: A total of 110 newly diagnosed oral cavity cancer patients requiring surgery as the primary modality were included in the study. Preoperative clinical examinations were done and tumor-node-metastasis staging was noted. Intraoperatively, Level IIb nodal tissue was dissected and sent separately. Results: A total of 129 neck dissections (58 SOHD, 67 modified neck dissections, and 4 radical neck dissections) were carried out in 110 patients (males = 80 and females = 30), 91 patients required unilateral neck dissection, and 19 patients required bilateral neck dissection. Out of these 129 neck dissections, only 4 (3.2%) neck dissections (in a total of 3 patients out of 110 patients) had Level IIb positive (with bilateral Level IIb involvement in one patient). Conclusions: Dissection of the Level IIb region in patients with OSCC may be required only in cases with advanced N stage, positive Level IIa lymph nodes, and extracapsular spread. Furthermore, in tongue cancers (high propensity of isolated Level II involvement), retromolar trigone, and floor of mouth cancers, routine Level IIb clearance should be considered.

10.
Tuberculosis (Edinb) ; 116S: S19-S27, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31078419

RESUMO

We have recently reported that in vitro and intracellular organic peroxide stress oxidizes OhrR of Mycobacterium smegmatis and that the oxidized OhrR consequently derepresses the expression of Ohr. Here we demonstrate that the OhrR-Ohr system is highly useful for the expression of recombinant mycobacterial proteins and also for the delivery of Mycobacterium tuberculosis (Mtb) antigens to the phagosomal compartments. Recombinant M. smegmatis strains, which bear plasmid constructs to express Ohr2-T85BCFP and Ohr2-MtrA, showed expression of fusion proteins upon induction with t-butyl hydroperoxide (t-BHP) in a dose dependent manner. The M. smegmatis expressed Ohr2-T85BCFP fusion could be affinity purified by adding a 9x histidine tag to the C-terminal end of the fusion protein. Further, mouse bone marrow derived macrophages (BMDMs) infected with either recombinant M. smegmatis or BCG strains with ohr2-T85BCFP construct showed expression of T85BCFP protein without any exogenously added inducer. In addition, BMDMs infected with either recombinant BCG or Mtb with ohr2-T85BCFP construct could effectively deliver the antigens to T-cells at higher levels than strains bearing the control plasmid alone. Altogether, these results suggest that the OhrR-Ohr system is a novel inducible system to study the biology and pathogenesis of mycobacteria.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/metabolismo , Fagossomos/metabolismo , Proteínas Repressoras/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Células Cultivadas , Regulação Bacteriana da Expressão Gênica , Histidina/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos Endogâmicos C57BL , Mycobacterium bovis/genética , Mycobacterium bovis/metabolismo , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Oligopeptídeos/metabolismo , Fagossomos/genética , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética
11.
Tuberculosis (Edinb) ; 116S: S34-S41, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31064713

RESUMO

Among the various strategies to improve vaccines against infectious diseases, targeting of antigens to dendritic cells (DCs), which are professional antigen presenting cells (APCs), has received increased attention in recent years. Here, we investigated whether a synthetic peptide region named RVG, originated from Rabies Virus Glycoprotein that binds to the α-7 subunit of the nicotinic acetylcholine receptors (AchR-α7) of APCs, could be used for the delivery of Mycobacterium tuberculosis (Mtb) peptide antigens to DCs and macrophages. Mouse bone marrow derived DCs (BMDCs) and human THP-1 macrophages stimulated with RVG fused peptide epitopes 85B241 and 85B96 (represent Ag85B241-256 and Ag85B96-111, respectively) from antigen 85B (Ag85B) of Mtb showed enhanced antigen presentation as compared to unfused peptide epitopes and BCG. Further, BMDCs stimulated with RVG fused 85B241 showed higher levels of IL-12 positive cells. Consistent with in vitro data, splenocytes of mice immunized with RVG-85B241 showed increased number of antigen specific IFN-γ, IL-2, and TNF-α producing cells in relation to splenocytes from mice immunized with 85B241 alone. These results suggest that RVG may be a promising tool to develop effective alternate vaccines against tuberculosis (TB).


Assuntos
Aciltransferases/metabolismo , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Células Dendríticas/metabolismo , Glicoproteínas/metabolismo , Macrófagos/metabolismo , Fragmentos de Peptídeos/metabolismo , Vacinas contra a Tuberculose/metabolismo , Tuberculose/prevenção & controle , Proteínas Virais/metabolismo , Aciltransferases/administração & dosagem , Aciltransferases/genética , Aciltransferases/imunologia , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Epitopos , Glicoproteínas/genética , Humanos , Imunização , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/genética , Proteínas Recombinantes de Fusão/metabolismo , Células THP-1 , Tuberculose/imunologia , Tuberculose/microbiologia , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/genética , Vacinas contra a Tuberculose/imunologia , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/metabolismo , Proteínas Virais/genética
12.
Sci Rep ; 7(1): 3922, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28634401

RESUMO

Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M. smegmatis strains bearing the pohr-gfpuv fusion construct were able to express GFP only in the absence of an intact ohrR gene, but not in its presence. However, GFP expression in the strain bearing pohr-gfpuv with an intact ohrR gene could be induced by organic hydroperoxides in vitro and in the intracellular environment upon ingestion of the bacteria by macrophages; indicating that OhrR responds not only to in vitro but also to intracellular organic hydroperoxide stress. Further, the intracellular expression of pohr driven GFP in this strain could be abolished by replacing the intact ohrR gene with a mutant ohrR gene modified for N-terminal Cysteine (Cys) residue, suggesting that OhrR senses intracellular organic hydroperoxides through Cys residue. This is the first report demonstrating the ability of OhrR to sense intracellular organic hydroperoxides.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peróxido de Hidrogênio/metabolismo , Mycobacterium smegmatis/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Animais , Células Cultivadas , Cisteína/genética , Cisteína/metabolismo , Regulação Bacteriana da Expressão Gênica , Macrófagos/microbiologia , Camundongos , Mutação , Mycobacterium smegmatis/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Estresse Fisiológico
13.
Tuberculosis (Edinb) ; 101S: S18-S27, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27727129

RESUMO

Tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. Unfortunately, the current BCG vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. With an aim to develop such vaccines, we have analyzed the utility of Bacillus subtilis spores for the expression of two major immunodominant antigens of Mycobacterium tuberculosis, Ag85B and CFP10. We created three recombinant B. subtilis strains to express a truncated fusion of Ag85B191-325 and CFP101-70 antigens (T85BCFP), either on the spore coat (MTAG1 strain) or in the cytosol of B. subtilis (MTAG 2 and MTAG 3 strains). Examination of spores isolated from these strains revealed successful expression of T85BCFP antigens on the spore coat of MTAG1 as well as in the cytosol of vegetatively grown cells of MTAG2 and MTAG3, indicating that spores can indeed express M. tuberculosis antigens. In vitro antigen presentation assays with spore-infected mouse bone marrow derived macrophages (BMDM) showed that all three recombinant spores could deliver these antigens to antigen presenting cells (APCs). Mice immunized with recombinant spores displayed significantly higher levels of Ag85B specific IFN-γ producing cells in the spleen than in mice immunized with wild-type (non-recombinant) spores. In addition, these mice showed relatively higher levels of Ag85B specific IgG antibodies in the serum in comparison to mice immunized with non-recombinant spores, thus providing additional evidence that recombinant spores can deliver these antigens in vivo. These results suggest that B. subtilis spores are ideal vehicles for antigen delivery and have great potential in the development of primary and booster vaccines against tuberculosis.


Assuntos
Aciltransferases/administração & dosagem , Antígenos de Bactérias/administração & dosagem , Bacillus subtilis/metabolismo , Proteínas de Bactérias/administração & dosagem , Vetores Genéticos , Esporos Bacterianos , Vacinas contra a Tuberculose/administração & dosagem , Aciltransferases/biossíntese , Aciltransferases/genética , Aciltransferases/imunologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Bacillus subtilis/genética , Bacillus subtilis/imunologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Células Cultivadas , Feminino , Imunidade Celular , Imunidade Humoral , Imunização , Imunoglobulina G/sangue , Interferon gama/imunologia , Interferon gama/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/imunologia , Baço/imunologia , Baço/metabolismo , Vacinas contra a Tuberculose/biossíntese , Vacinas contra a Tuberculose/genética , Vacinas contra a Tuberculose/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/biossíntese , Vacinas Sintéticas/imunologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-27536558

RESUMO

MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside host cells. In this review, we present an overview of the recent findings on alterations of miRNAs in the host cells by facultative intracellular bacterial pathogens. In addition, we discuss how the altered miRNAs help in the survival of these pathogens in the intracellular environment.


Assuntos
Bactérias/metabolismo , MicroRNAs/metabolismo , Animais , Bactérias/imunologia , Bactérias/patogenicidade , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Citoplasma/imunologia , Citoplasma/metabolismo , Citoplasma/microbiologia , Interações Hospedeiro-Parasita , Humanos , Imunidade Inata , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Redes e Vias Metabólicas , MicroRNAs/genética , MicroRNAs/imunologia
16.
J. pediatr. (Rio J.) ; 91(5): 471-477, Sept.-Oct. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-766177

RESUMO

ABSTRACT OBJECTIVE: To evaluate socio-economic and demographic determinants of anemia among Indian children aged 6-59 months. METHODS: Statistical analysis was performed on the cross-sectional weighted sample of 40,885 children from 2005 to 2006 National Family Health Survey by using multinomial logistic regression to assess the significance of some risk factors in different degrees of child anemia. Anemia was diagnosed by World Health Organization (WHO) cut-off points on hemoglobin level. Pearson's chi-squared test was applied to justify the associations of anemia with different categories of the study population. RESULTS: The prevalence of anemia was 69.5%; 26.2% mild, 40.4% moderate, and 2.9% severe anemia. Overall prevalence rate, along with mild and moderate cases, showed an increasing trend up to 2 years of age and then decreased. Rural children had a higher prevalence rate. Of 28 Indian states in the study, 10 states showed very high prevalence, the highest being Bihar (77.9%). Higher birth order, high index of poverty, low level of maternal education, mother's anemia, non-intake of iron supplements during pregnancy, and vegetarian mother increased the risks of all types of anemia among children (p < 0.05). Christian population was at lower risk; and Scheduled Caste, Scheduled Tribe, and Other Backward Class categories were at higher risk of anemia. CONCLUSION: The results suggest a need for proper planning and implementation of preventive measures to combat child anemia. Economically under-privileged groups, maternal nutrition and education, and birth control measures should be priorities in the programs.


RESUMO OBJETIVO: Avaliar os fatores socioeconômicos e demográficos determinantes de anemia em crianças indianas de seis a 59 meses. MÉTODOS: A análise estatística foi feita na amostra transversal ponderada de 40.885 crianças da Pesquisa Nacional de Saúde da Família de 2005-2006, Governo da Índia, com a técnica de regressão logística multimodal para avaliar a relevância de alguns fatores de risco em diferentes graus de anemia infantil. A anemia foi diagnosticada pelos pontos de corte de nível de hemoglobinas da OMS. O teste qui-quadrado de Pearson foi usado para justificar as associações da anemia com diferentes categorias de população estudada. RESULTADOS: A prevalência de anemia foi de 69,5%, 26,2% de anemia leve, 40,4% de anemia moderada e 2,9% de anemia grave. A taxa de prevalência geral, juntamente com a de anemia leve e moderada, mostrou uma tendência de aumento até os dois anos e depois disso de queda. As crianças da zona rural têm maior taxa de prevalência. Dos 28 estados indianos do estudo, 10 apresentaram prevalência muito alta. Bihar foi o maior deles (77,9%). A ordem de nascimento elevada, o alto índice de pobreza, o baixo nível de escolaridade materna, a anemia materna, a não ingestão de suplementos de ferro durante a gravidez e o vegetarianismo materno aumentaram os riscos de todos os tipos de anemia entre crianças (p < 0,05). A população cristã tinha o menor risco; e as categorias casta reconhecida, tribo reconhecida e outras classes atrasadas tinham o maior risco de anemia. CONCLUSÃO: Os resultados sugerem a necessidade de planejamento e implantação adequados de medidas preventivas contra a anemia infantil. Grupos economicamente carentes, a nutrição e a escolaridade maternas e o controle da natalidade devem ser prioridades nos programas.


Assuntos
Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anemia/epidemiologia , Fatores Socioeconômicos , Ordem de Nascimento , Estudos Transversais , Hemoglobinas/análise , Índia/epidemiologia , Prevalência , Religião , Fatores de Risco , População Rural/estatística & dados numéricos , Distribuição por Sexo
17.
J Pediatr (Rio J) ; 91(5): 471-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26070864

RESUMO

OBJECTIVE: To evaluate socio-economic and demographic determinants of anemia among Indian children aged 6-59 months. METHODS: Statistical analysis was performed on the cross-sectional weighted sample of 40,885 children from 2005 to 2006 National Family Health Survey by using multinomial logistic regression to assess the significance of some risk factors in different degrees of child anemia. Anemia was diagnosed by World Health Organization (WHO) cut-off points on hemoglobin level. Pearson's chi-squared test was applied to justify the associations of anemia with different categories of the study population. RESULTS: The prevalence of anemia was 69.5%; 26.2% mild, 40.4% moderate, and 2.9% severe anemia. Overall prevalence rate, along with mild and moderate cases, showed an increasing trend up to 2 years of age and then decreased. Rural children had a higher prevalence rate. Of 28 Indian states in the study, 10 states showed very high prevalence, the highest being Bihar (77.9%). Higher birth order, high index of poverty, low level of maternal education, mother's anemia, non-intake of iron supplements during pregnancy, and vegetarian mother increased the risks of all types of anemia among children (p<0.05). Christian population was at lower risk; and Scheduled Caste, Scheduled Tribe, and Other Backward Class categories were at higher risk of anemia. CONCLUSION: The results suggest a need for proper planning and implementation of preventive measures to combat child anemia. Economically under-privileged groups, maternal nutrition and education, and birth control measures should be priorities in the programs.


Assuntos
Anemia/epidemiologia , Fatores Socioeconômicos , Ordem de Nascimento , Pré-Escolar , Estudos Transversais , Feminino , Hemoglobinas/análise , Humanos , Índia/epidemiologia , Lactente , Masculino , Prevalência , Religião , Fatores de Risco , População Rural/estatística & dados numéricos , Distribuição por Sexo
18.
Asian Pac J Cancer Prev ; 16(11): 4715-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26107229

RESUMO

BACKGROUND: Patient delay can contribute to a poor outcome in the management of head and neck cancers (HNC). The main objective of the present study was to investigate the factors associated with patient delay in our population. MATERIALS AND METHODS: Patients with cancers of the head and neck attending a regional cancer center of North East India were consecutively interviewed during the period from June 2014 to November 2014. The participation of patients was voluntary. The questionnaire included information on age, gender, residential status, educational qualification, monthly family income, any family history of cancer, and history of prior awareness on cancer from television (TV) program and awareness program. RESULTS: Of 311 (n) patients, with an age range of 14-88 years (mean 55.4 years), 81.7% were males and 18.3% females (M:F=4.4). The overall median delay was 90 days (range=7 days-365 days), in illiterate patients the median delay was 90 days and 60 days in literate patients (P=0.002), the median delay in patients who had watched cancer awareness program on TV was 60 days and in patients who were unaware about cancer information from TV program had a median delay of 90 days (p=0.00021) and delay of <10 weeks was seen in 139 (44.6%) patients, a delay of 10-20 weeks in 98 (31.5%) patients, and a delay of 20-30 weeks in 63 (20.2%) patients. CONCLUSIONS: Education and awareness had a significant impact in reduction of median patient delay in our HNC cases.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Tardio , Neoplasias de Cabeça e Pescoço/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Disparidades em Assistência à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
19.
Burns ; 41(6): 1315-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25716761

RESUMO

Malignant transformation on any scar tissue is known as Marjolin's ulcer. Most cases of Marjolin's ulcer reported so far occur in post-burn scars but not all ulcers that occur in post-burn scar are malignant. One hundred and forty cases of chronic non-healing ulcers in post-burn scar were included in this prospective observational study. The study was conducted in the Department of Burn and Plastic Surgery Unit of Dhaka Medical College Hospital. Mean age of the patients was 40.63±18.44 with a range from 12 to 75 years. Two third of the patients were male. All patients underwent excision biopsy and coverage with either split thickness skin graft or flap. Histopathological analysis of the resected specimen revealed malignancy in 46 cases and pseudoepitheliomatous hyperplasia in four cases and verruca plantaris in one case. The rest of the cases were chronic non-healing benign ulcers. All 46 cases of Marjolin's ulcer were squamous cell carcinoma with a mean latency period of 26.73 years. The commonest site of chronic ulcer was in the lower extremities (n-80, 57%), and malignancy was also found to be more common there (n-18). The most common type of burn was flame burn (68.57%). The Marjolin's ulcers were significantly larger in size than benign ulcers, and were mostly exophytic or ulcerative in appearance whereas benign ulcers were mostly flat. A non-healing ulcer in a post-burn scar should be addressed promptly because of its potential to develop into a malignant ulcer. Emphasis should be given to early surgical treatment of deep partial to full thickness burns to prevent scar formation, particularly over joints, and thus reduce the risk of development of Marjolin's ulcer.


Assuntos
Queimaduras/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Cicatriz/epidemiologia , Neoplasias Cutâneas/epidemiologia , Úlcera Cutânea/epidemiologia , Adolescente , Adulto , Idoso , Bangladesh/epidemiologia , Biópsia , Queimaduras/complicações , Criança , Cicatriz/etiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Transplante de Pele , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Adulto Jovem
20.
Burns ; 41(3): 484-92, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25440856

RESUMO

Acid burn injuries in Bangladesh primarily occur as a result of intentional attacks although there are incidences of accidental acid burns in industry, on the street, and at home. A total of 126 patients with acid burns, 95 from attacks and 31 from accidents, were studied from July 2004 to December 2012. A diagnosis of acid burn was made from history, physical examination and in some cases from chemical analysis of the patients' clothing. Alkali burns were excluded from the study. In the burn unit of Dhaka Medical College Hospital, we applied a slightly different protocol for management of acid burns, beginning with plain water irrigation of the wound, which effectively reduced burn depth and the requirement of surgical treatment. Application of hydrocolloid dressing for 48-72 h helped with the assessment of depth and the course of treatment. Early excision and grafting gives good results but resultant acid trickling creates a marble cake-like appearance of the wound separated by the vital skin. Excision with a scalpel and direct stitching of the wounds are often a good option. Observation of patients on follow-up revealed that wounds showed a tendency for hypertrophy. Application of pressure garments and other scar treatments were given in all cases unless the burn was highly superficial.


Assuntos
Acidentes/estatística & dados numéricos , Ácidos , Curativos Hidrocoloides , Queimaduras Químicas/terapia , Bandagens Compressivas , Transplante de Pele , Violência/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Bangladesh/epidemiologia , Queimaduras Químicas/epidemiologia , Criança , Estudos de Coortes , Vítimas de Crime/estatística & dados numéricos , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
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