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1.
Oncogene ; 38(30): 5873-5889, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31253871

RESUMO

Cutaneous melanoma is one of the most aggressive cancers characterized by a high plasticity, a propensity for metastasis, and drug resistance. Melanomas are composed of phenotypically diverse subpopulations of tumor cells with heterogeneous molecular profiles that reflect intrinsic invasive abilities. In an attempt to identify novel factors of the melanoma invasive cell state, we previously investigated the nature of the invasive secretome by using a comparative proteomic approach. Here, we have extended this analysis to show that PTX3, an acute phase inflammatory glycoprotein, is one such factor secreted by invasive melanoma to promote tumor cell invasiveness. Elevated PTX3 production was observed in the population of MITFlow invasive cells but not in the population of MITFhigh differentiated melanoma cells. Consistently, MITF knockdown increased PTX3 expression in MITFhigh proliferative and poorly invasive cells. High levels of PTX3 were found in tissues and blood of metastatic melanoma patients, and in BRAF inhibitor-resistant melanoma cells displaying a mesenchymal invasive MITFlow phenotype. Genetic silencing of PTX3 in invasive melanoma cells dramatically impaired migration and invasion in vitro and in experimental lung extravasation assay in xenografted mice. In contrast, addition of melanoma-derived or recombinant PTX3, or expression of PTX3 enhanced motility of low migratory cells. Mechanistically, autocrine production of PTX3 by melanoma cells triggered an IKK/NFκB signaling pathway that promotes migration, invasion, and expression of the EMT factor TWIST1. Finally, we found that TLR4 and MYD88 knockdown inhibited PTX3-induced melanoma cell migration, suggesting that PTX3 functions through a TLR4-dependent pathway. Our work reveals that tumor-derived PTX3 contributes to melanoma cell invasion via targetable inflammation-related pathways. In addition to providing new insights into the biology of melanoma invasive behavior, this study underscores the notion that secreted PTX3 represents a potential biomarker and therapeutic target in a subpopulation of MITFlow invasive and/or refractory melanoma.


Assuntos
Proteína C-Reativa/fisiologia , Melanoma/metabolismo , NF-kappa B/metabolismo , Metástase Neoplásica/fisiopatologia , Componente Amiloide P Sérico/fisiologia , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Melanoma/patologia , Camundongos , Invasividade Neoplásica , Neoplasias Cutâneas/patologia , Regulação para Cima , Melanoma Maligno Cutâneo
2.
J Microencapsul ; 35(2): 181-191, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29544365

RESUMO

The aim of the present study is to develop embelin-loaded guar gum microparticles through emulsification technique. The in vitro release of the optimised formulation was found to be 88.5 ± 3.8% in 24 h, has exhibited remarkably sustain and delayed the release of embelin at a specific site. Embelin-loaded microparticles showed average particle size of 12.9 ± 0.75 µm. The statistical analysis was carried out by one-way ANOVA followed by comparison test of Bonferroni. P values < 0.05 were considered as significant. The in vivo study concluded that pre-treatment of embelin prevents dinitrobenzenesulfonic acid (DNBS)-induced colitis in rats and depicts protective activity against ulcerative colitis due to its antioxidant and anti-inflammatory actions. This approach produces comparatively less side effect to another conventional dosage form.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Benzoquinonas/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Preparações de Ação Retardada/química , Galactanos/química , Mananas/química , Gomas Vegetais/química , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Benzoquinonas/farmacocinética , Benzoquinonas/uso terapêutico , Colite Ulcerativa/patologia , Colite Ulcerativa/prevenção & controle , Colo/efeitos dos fármacos , Colo/patologia , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula , Ratos Wistar
3.
J Microencapsul ; 35(2): 137-148, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29448848

RESUMO

The aim of this study was to prepare and characterise oral delivery of morin hydrate-loaded micellar nanocarriers using Pluronic P127 and Pluronic F123 for the effective management of Alzheimer's disease. After administration of formulation brain and blood drug concentration were found to be highest for optimised morin hydrate-loaded micellar nanocarriers as compared to plain morin hydrate. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after administration of morin hydrate-loaded micellar nanocarriers as compared to disease control group. Chronic treatment with morin-loaded micelles significantly increased the memory in AlCl3 induced Alzheimer's disease in Wistar rats.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/administração & dosagem , Portadores de Fármacos/química , Flavonoides/administração & dosagem , Poloxâmero/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Flavonoides/farmacocinética , Flavonoides/uso terapêutico , Locomoção/efeitos dos fármacos , Memória/efeitos dos fármacos , Micelas , Ratos Wistar
4.
Updates Surg ; 69(1): 21-28, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28124278

RESUMO

This article highlights the clinical effectiveness of wound edge protector devices (WEPD) in preventing the post-operative surgical site infections (SSI) in patients undergoing abdominal surgery. Using the principles of meta-analysis and systematic review as recommended by the Cochrane Collaboration, the data from selected randomized, controlled trials (RCTs) were analysed to generate summated outcome and presented in the form of odds ratio (OR). Eighteen RCTs on 3808 reported the effectiveness of WEPD in patients undergoing abdominal surgery. The use of WEPD was associated with the reduced incidence of overall SSI (OR 0.59; 95% CI 0.43-0.81; z = 3.30; p < 0.001) and superficial SSI (OR 0.42; 95% CI 0.18-0.95; z = 2.09; p < 0.04). In addition, WEPD also successfully reduced the risk of SSI in clean-contaminated wounds (OR 0.67; 95% CI 0.46-0.98; z = 2.06; p < 0.04) as well as in contaminated wounds (OR 0.24; 95% CI 0.12-0.49; z = 3.96; p < 0.0001). WEPD seems to be an effective intervention to reduce the risk of post-operative SSI in patients undergoing abdominal surgery.


Assuntos
Abdome/cirurgia , Instrumentos Cirúrgicos , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos
5.
J Med Syst ; 40(12): 283, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27796839

RESUMO

Healthy people are important for any nation's development. Use of the Internet of Things (IoT)-based body area networks (BANs) is increasing for continuous monitoring and medical healthcare in order to perform real-time actions in case of emergencies. However, in the case of monitoring the health of all citizens or people in a country, the millions of sensors attached to human bodies generate massive volume of heterogeneous data, called "Big Data." Processing Big Data and performing real-time actions in critical situations is a challenging task. Therefore, in order to address such issues, we propose a Real-time Medical Emergency Response System that involves IoT-based medical sensors deployed on the human body. Moreover, the proposed system consists of the data analysis building, called "Intelligent Building," depicted by the proposed layered architecture and implementation model, and it is responsible for analysis and decision-making. The data collected from millions of body-attached sensors is forwarded to Intelligent Building for processing and for performing necessary actions using various units such as collection, Hadoop Processing (HPU), and analysis and decision. The feasibility and efficiency of the proposed system are evaluated by implementing the system on Hadoop using an UBUNTU 14.04 LTS coreTMi5 machine. Various medical sensory datasets and real-time network traffic are considered for evaluating the efficiency of the system. The results show that the proposed system has the capability of efficiently processing WBAN sensory data from millions of users in order to perform real-time responses in case of emergencies.


Assuntos
Serviços Médicos de Emergência/organização & administração , Internet , Informática Médica/organização & administração , Saúde Pública , Tecnologia de Sensoriamento Remoto/métodos , Algoritmos , Humanos , Modelos Teóricos , Fatores de Tempo
6.
Sci Rep ; 6: 24176, 2016 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-27072282

RESUMO

Weedy rice, a menace in rice growing areas globally, is biosimilar having attributes similar to cultivated and wild rice, and therefore is difficult to manage. A study was initiated to characterize the functional traits of 76 weedy rice populations and commonly grown rice cultivars from different agro-climatic zones for nine morphological, five physiological, and three phenological parameters in a field experiment under an augmented block design. Comparison between weedy and cultivated rice revealed a difference in duration (days) from panicle emergence to heading as the most variable trait and awn length as the least variable one, as evidenced from their coefficients of variation. The results of principal component analysis revealed the first three principal components to represent 47.3% of the total variation, which indicates an important role of transpiration, conductance, leaf-air temperature difference, days to panicle emergence, days to heading, flag leaf length, SPAD (soil-plant analysis development), grain weight, plant height, and panicle length to the diversity in weedy rice populations. The variations existing in weedy rice population are a major reason for its wider adaptability to varied environmental conditions and also a problem while trying to manage it.


Assuntos
Variação Genética , Oryza/genética , Característica Quantitativa Herdável , Oryza/fisiologia
7.
J Clin Diagn Res ; 10(11): AD03-AD04, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28050355

RESUMO

Human hand is involved in variety of precision work which requires a combined effort of forearm muscles as well as intrinsic muscles of hand. Lumbricals along with interossei muscles connect the tendons of flexor and extensor muscles and thus play a key role in the characteristic movements of human hands. Lumbricals originate from long flexor tendon and is inserted into dorsal digital expansion. Any variation in the attachment of these muscles can lead to deviation from the normal actions of the fingers and their proximal extension into carpal tunnel and might lead to carpal tunnel syndrome. An extremely rare case of first lumbrical taking origin solely from first tendon of Flexor Digitorum Superficialis (FDS) and having proximal attachment extending into carpal tunnel was noticed bilaterally in cadaveric dissection. These variations are always challenging for clinicians and surgeons during hand surgeries.

8.
Public Health ; 131: 71-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26652710

RESUMO

OBJECTIVE: To study trends in human immunodeficiency virus (HIV) seroprevalence in blood donors in northern Pakistan. STUDY DESIGN: Analysis of annual data from blood transfusion centre. PLACE AND DURATION OF STUDY: Data records from people who had donated blood at the Armed Forces Institute of Transfusion (AFIT) between 1998 and 2013 were retrieved and analysed. METHODS: All blood donations were tested for the presence of HIV antibodies using Abbott Inc's AxSYM from 1998 to 2006, and Abbott Inc's Architect 2000i with chemiluminescence microplate immunoassay from 2007 to 2013. RESULTS: Over the 16-year study period, 66 donors tested positive for HIV antibodies out of 626,413 donations (0.01%, i.e. 10 per 100,000 donations). From 1998 to 2006, 16 HIV-positive cases were detected out of 280,245 donations (0.0057%, i.e. 5.7 per 100,000 donations). However, from 2007 to 2013, 50 HIV-positive cases were detected out of 346,168 donations (0.0144%, i.e. 14 per 100,000 donations). The difference in HIV positivity between the two groups was found to be significant (0.0057% vs 0.0144%, χ(2) = 10.4, P = 0.008). CONCLUSION: A gradual and persistent increase in the number of HIV-positive cases among blood donors in northern Pakistan was seen over the study period. The HIV-positive cases reported one or more high-risk activities in the past which predisposed them to HIV infection.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Infecções por HIV/epidemiologia , Soroprevalência de HIV/tendências , Doadores de Sangue/psicologia , Feminino , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/isolamento & purificação , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Paquistão/epidemiologia , Assunção de Riscos
9.
Pak J Med Sci ; 31(1): 127-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25878628

RESUMO

OBJECTIVES: The aim of present study was to investigate serum homocysteine levels in apparently healthy vegetarians and ominvores in Mithi, district Tharparker, Sindh, Pakistan. METHODS: This study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi and blood samples were collected from Mithi, district Tharparker, Sindh, Pakistan, in 2012. One hundred vegetarian and one hundred omnivores (age ranging from 20-40 years) were enrolled for this study. Serum homocysteine levels were measured by the chemiluminescence enzyme immunoassay method. RESULTS: Serum homocysteine (Hcy) level was considerably higher (p<0.001) in vegetarian group compared to omnivores. We further grouped and analyzed our study subjects according to their gender and according to Hcy level (greater than or lower than 15µmol/L). A considerable number of vegetarian subjects 30% were having Hcy >15µmol/L compared to omnivores 6%, (p<0.001). Gender-wise comparison showed that 27.02% male and 38.46% females had >15µmol/L serum Hcy level in vegetarian group and 6.9% male and 3.5% females had >15µmol/L serum Hcy level in omnivores group, but the difference was not significant in any group. CONCLUSION: Vegetarians are more prone to develop hyperhomocysteinemia, so they are at high risk to develop cardiovascular disease.

10.
Eur Rev Med Pharmacol Sci ; 18(12): 1687-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24992606

RESUMO

Acute pancreatitis (AP) is relatively uncommon in pediatric age group. Traumatic injury is an important cause of AP in children. Ductal disruption resulting from pancreatic trauma usually needs surgical intervention. A three-and-a-half year old child presented with complaints of abdominal pain and distension following blunt trauma abdomen. Computed tomography of abdomen revealed presence of grade III pancreatic injury with fluid collection in lesser sac. The patient was managed with antibiotics and pigtail drainage and he improved. Therapy for traumatic pancreatitis in paediatric patients must be individualised. Even high grade injuries can be managed non-operatively.


Assuntos
Pâncreas/lesões , Pancreatite/terapia , Ferimentos não Penetrantes/terapia , Dor Abdominal/etiologia , Antibacterianos/uso terapêutico , Cateterismo , Pré-Escolar , Humanos , Masculino , Pancreatite/etiologia , Vômito/etiologia , Ferimentos não Penetrantes/complicações
11.
Indian J Chest Dis Allied Sci ; 56(1): 49-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24930209

RESUMO

Isolated unilateral absence of pulmonary artery (UAPA) is a rare congenital anomaly. When detected in infancy, the condition is commonly associated with cardiovascular defects which are more frequently associated with left pulmonary artery agenesis. Patients with isolated right pulmonary artery agenesis survive into adulthood with minimal or no symptoms and are diagnosed incidentally on the chest radiographs. We report a case of a 19-year-old female patient who presented to us with recurrent haemoptysis. She was symptomatic since the age of four years. We report the rare occurrence of UAPA on right side, agenesis of right upper lobe and bronchiectasis of right lower lobe with anomalous arterial supply of right lung from coeliac axis in this patient.


Assuntos
Anormalidades Múltiplas , Bronquiectasia/etiologia , Artéria Celíaca/anormalidades , Hemoptise/etiologia , Artéria Hepática/anormalidades , Pulmão/anormalidades , Artéria Pulmonar/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Angiografia , Bronquiectasia/diagnóstico , Bronquiectasia/diagnóstico por imagem , Artéria Celíaca/diagnóstico por imagem , Feminino , Seguimentos , Hemoptise/terapia , Artéria Hepática/diagnóstico por imagem , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Recidiva , Tomografia Computadorizada por Raios X , Recusa do Paciente ao Tratamento
12.
Dis Esophagus ; 27(3): 203-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23796367

RESUMO

Increasingly frequent dilation may become a self-defeating cycle in refractory stricture as recurrent trauma enhance, scar formation, and ultimately recurrence and potential worsening of the stricture. In 12 patients of caustic induced esophageal stricture, who failed to respond despite rigorous dilatation regimen for more than one year, a trial of topical mitomycin-C application to improve dilatation results was undertaken, considering the recently reported efficacy and safety of this agent. Mitomycin-C was applied for 2-3 minutes at the strictured esophageal segment after dilation with wire-guided Savary-Gilliard dilator. Patient was kept nil by mouth for 2-3 hours. After 4-6 sessions of mitomycin-C treatment, resolution of symptoms and significant improvement in dysphagia score and periodic dilatation index was seen in all 12 patients. Mitomycin-C topical application may be a useful strategy in refractory corrosive esophageal strictures and salvage patients from surgery.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Transtornos de Deglutição/etiologia , Estenose Esofágica/tratamento farmacológico , Mitomicina/uso terapêutico , Administração Tópica , Antibióticos Antineoplásicos/administração & dosagem , Queimaduras Químicas/complicações , Dilatação/instrumentação , Estenose Esofágica/etiologia , Humanos , Mitomicina/administração & dosagem , Recidiva , Índice de Gravidade de Doença , Falha de Tratamento
13.
J Clin Pediatr Dent ; 37(4): 373-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24046984

RESUMO

AIM: The present study evaluated the inflammatory/irritant potential of propolis in comparison with commonly used intracanal irrigants such as chlorhexidine and calcium hydroxide, with normal saline solution as control using an animal (Wistar rats) model. METHOD: 2% Evans blue was intravenously injected into the lateral caudal vein. 0.1 ml each of the test solutions was intradermally injected into the experimental sites designed on their shaved backs. The animals were then sacrificed after 1 1/2 and 3 hours respectively. Each piece of skin containing the injected solution was excised, immersed in 4 ml formamide and incubated at 45 degrees C for 72 hours. After filtration with glass wool, optical density(OD) was measured using a spectro-photometer and analyzed statistically. RESULTS: At 620 nm irrespective of time, the mean optical density with Calcium Hydroxide was found to be maximum (0.197 +/- 0.095) while that with DMSO Propolis was found to be minimum (0.070 +/- 0.016). Both at 90 min and 180 min, the mean optical density with Calcium Hydroxide was found to be maximum. CONCLUSIONS: On short-term evaluation, maximum inflammation was seen with calcium hydroxide followed by chlorhexidine and DMSO extract of propolis. Minimum inflammation was seen with sterile physiologic saline. With progress of time, maximum inflammation was seen with calcium hydroxide followed by chlorhexidine and DMSO extract of propolis which was non-significant.


Assuntos
Própole/toxicidade , Irrigantes do Canal Radicular/toxicidade , Pele/efeitos dos fármacos , Animais , Hidróxido de Cálcio/toxicidade , Clorexidina/toxicidade , Feminino , Inflamação/induzido quimicamente , Masculino , Ratos , Ratos Wistar
14.
J Clin Pediatr Dent ; 37(3): 243-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23855167

RESUMO

UNLABELLED: The objective of endodontic therapy is not just simple cleaning and filling of root canals, but successful treatment requires the establishment of a sufficient level of disinfection. AIM: To evaluate, in vivo, the antimicrobial and inflammatory/irritant potential of Propolis against mixed endodontic aerobic and anaerobic bacteria. METHOD: An in vivo randomized controlled trial was conducted in a group of 60 children aged 6-12 years presenting with an acute apical abscess of the maxillary primary molars. Fifteen children each were divided randomly into four groups where irrigation during pulpectomy was performed using either 2% chlorhexidine, 4% calcium hydroxide or 4% Dimethyl Sulfoxide (DMSO) extract of propolis with normal saline as the control irrigant. Microbiological samples were taken from the disto-buccal root canal before initiating the pulpectomy as well as after 3 days later and for mixed aerobic and anaerobic bacterial cultures. RESULTS: In all the four groups, a significant decrease in mean aerobic colony forming units (cfu) count was seen. Maximum change in anaerobic cfu count was seen with 2% chlorhexidine. CONCLUSIONS: Chlorhexidine proved to be superior antimicrobial agent against both endodontic aerobes and anaerobes. Calcium hydroxide was found to be least effective.


Assuntos
Anti-Infecciosos/uso terapêutico , Cavidade Pulpar/microbiologia , Própole/uso terapêutico , Irrigantes do Canal Radicular/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Anaeróbias/efeitos dos fármacos , Carga Bacteriana/efeitos dos fármacos , Hidróxido de Cálcio/uso terapêutico , Criança , Clorexidina/uso terapêutico , Dimetil Sulfóxido , Feminino , Humanos , Masculino , Dente Molar/microbiologia , Dente Molar/patologia , Abscesso Periapical/microbiologia , Abscesso Periapical/terapia , Pulpectomia/métodos , Solventes , Dente Decíduo/microbiologia , Dente Decíduo/patologia
15.
J Indian Med Assoc ; 110(2): 115-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23029846

RESUMO

The caruncle is nodular structure lying at internal canthus medial to plica semilunaris. It is composed of elements of conjunctiva, cutaneous and lacrimal tissue. In spite of its diverse histopathology, lesions of caruncle are rare and malignant melanoma is further rarer. This tumour is potentially lethal, even after prompt and proper treatment, especially after delayed onset of therapy. Clinical metastases usually occur first to the lymph nodes in approximately 45% to 60% of patients with regional metastases. Eventually systemic dissemination may occur to lung, brain, liver, skin, bone and the gastrointestinal tract, although this often arises without prior clinical evidence of regional lymph node involvement. Here a rare case of huge malignant melanoma of caruncle with extensive involvement of plica semilunaris, fornix and palpebral conjuctiva in a 58-years old male is reported who was treated with local excision combined with cryotherapy and topical 0.02% mitomycin-C eye drops.


Assuntos
Neoplasias da Túnica Conjuntiva/patologia , Melanoma/patologia , Antibióticos Antineoplásicos/administração & dosagem , Terapia Combinada , Neoplasias da Túnica Conjuntiva/cirurgia , Crioterapia , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Mitomicina/administração & dosagem
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