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Uterine leiomyomas, or fibroids, are common, benign tumors for which hysterectomy is the only definitive treatment. The extracellular matrix of fibroids is disorganized and stiffer than the surrounding myometrial tissue. To understand how stiffness affects fibroid cells, patient-matched fibroid and myometrial cells were cultured on substrates with stiffnesses varying from 0.2 to 150 kPa. Fibroid cells grew more slowly than myometrial cells overall, and only the myometrial cells altered their growth rate in response to stiffness. In both cell types, cell proliferation decreased with inhibition of PI3K and increased with inhibition of IGF-1. The cellular area was greater for the fibroid cells. The only significant effect of stiffness on the cell area was between the 0.2 and 64 kPa substrates, and this was true for both cell types. To investigate intracellular stiffness, intracellular particle tracking microrheology was used. Fibroid cells exhibited a more than 100-fold increase in elastic modulus at a frequency of 1 Hz in response to the addition of external stress, while myometrial cells showed little change in elastic modulus. Overall, the responses of both cells followed similar trends in response to stiffness and inhibitors, although the response was attenuated in the fibroid cells. The changes that were demonstrated by the change in intracellular stiffness with response to compression suggest that other mechanical forces may provide insight into differences in the two cell types.
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Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/metabolismo , Sinais (Psicologia) , Leiomioma/metabolismo , Miométrio/metabolismo , HisterectomiaRESUMO
BACKGROUND: Surgical site infection (SSI) is the most common complication of abdominal surgery, with substantial costs to patients and health systems. Heterogeneity in costing methods in existing SSI studies makes multi-country comparison challenging. The objective of the study was to assess the costs of SSI across middle-income countries. METHODS: Centres from a randomized controlled trial assessing interventions to reduce SSI (FALCON, ClinicalTrials.gov, NCT03700749NCT) were sampled from two upper-middle- (India, Mexico) and two lower-middle- (Ghana, Nigeria) income countries. The Key resource use In Wound Infection (KIWI) study collected data on postoperative resource use and costs from consecutive patients undergoing abdominal surgery with an incision >5 cm (including caesarean section) that were recruited to FALCON between April and October 2020. The overall costs faced by patients with and without SSI were compared by operative field contamination (clean-contaminated vs contaminated-dirty), country and timing (inpatient vs outpatient). FINDINGS: A total of 335 patients were included in KIWI; SSI occurred in 7% of clean-contaminated cases and 27% of contaminated-dirty cases. Overall, SSI was associated with an increase in postoperative healthcare costs by 75.3% (412 international Euros) after clean-contaminated surgery and 66.6% (331) after contaminated-dirty surgery. The highest and lowest cost increases were in India for clean-contaminated cases (517) and contaminated-dirty cases (223), respectively. Overall, inpatient costs accounted for 96.4% of the total healthcare costs after clean-contaminated surgery and 92.5% after contaminated-dirty surgery. CONCLUSION: SSI was associated with substantial additional postoperative costs across a range of settings. Investment in health technologies to reduce SSI may mitigate the financial burden to patients and low-resource health systems.
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Países em Desenvolvimento , Infecção da Ferida Cirúrgica , Feminino , Humanos , Gravidez , Cesárea/efeitos adversos , Coleta de Dados , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologiaRESUMO
The animal model deals with the species other than the human, as it can imitate the disease progression, its' diagnosis as well as a treatment similar to human. Discovery of a drug and/or component, equipment, their toxicological studies, dose, side effects are in vivo studied for future use in humans considering its' ethical issues. Here lies the importance of the animal model for its enormous use in biomedical research. Animal models have many facets that mimic various disease conditions in humans like systemic autoimmune diseases, rheumatoid arthritis, epilepsy, Alzheimer's disease, cardiovascular diseases, Atherosclerosis, diabetes, etc., and many more. Besides, the model has tremendous importance in drug development, development of medical devices, tissue engineering, wound healing, and bone and cartilage regeneration studies, as a model in vascular surgeries as well as the model for vertebral disc regeneration surgery. Though, all the models have some advantages as well as challenges, but, present review has emphasized the importance of various small and large animal models in pharmaceutical drug development, transgenic animal models, models for medical device developments, studies for various human diseases, bone and cartilage regeneration model, diabetic and burn wound model as well as surgical models like vascular surgeries and surgeries for intervertebral disc degeneration considering all the ethical issues of that specific animal model. Despite, the process of using the animal model has facilitated researchers to carry out the researches that would have been impossible to accomplish in human considering the ethical prohibitions.
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OBJECTIVE: To assess the effect of tranexamic acid on intra-operative bleeding and surgical field visualisation. METHODS: Fifty patients undergoing various endoscopic ear surgical procedures, including endoscopic tympanoplasty, endoscopic atticotomy or mastoidectomy, endoscopic ossiculoplasty, and endoscopic stapedotomy, were randomly assigned to: a study group that received tranexamic acid or a control group which received normal saline. The intra-operative bleeding and operative field visualisation was graded using the Das and Mitra endoscopic ear surgery bleeding and field visibility score, which was separately analysed for the external auditory canal and the middle ear. RESULTS: The Das and Mitra score was better (p < 0.05) in the group that received tranexamic acid as a haemostat when working in the external auditory canal; with respect to the middle ear, no statistically significant difference was found between the two agents. Mean values for mean arterial pressure, heart rate and surgical time were comparable in both groups, with no statistically significant differences. CONCLUSION: Tranexamic acid appears to be an effective haemostat in endoscopic ear surgery, thus improving surgical field visualisation, especially during manipulation of the external auditory canal soft tissues.
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Antifibrinolíticos/uso terapêutico , Meato Acústico Externo/cirurgia , Endoscopia/métodos , Procedimentos Cirúrgicos Otológicos/métodos , Ácido Tranexâmico/uso terapêutico , Adolescente , Adulto , Pontos de Referência Anatômicos/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Método Duplo-Cego , Meato Acústico Externo/anatomia & histologia , Feminino , Hemostasia Cirúrgica/métodos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and also the expression of p53 and RARß together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials and Methods: Immunohistochemical staining was performed on 100 cases of cervical pre- neoplastic lesions for expression of biomarkers like p16, p53 and RARß for comparison with haematoxylin/eosin (HE) findings. All the experimentally generated data were statistically analyzed. Results: In this study 70% cases showed overexpression of p16INK4A increasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seen in 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% cases showed negative immunoreactivity for the putative tumor suppressor gene RARß (p>0.05). Conclusion: Our study provides support for the idea that p16 can be used to identify associations with HPV , as well as having potential along with p53 and RARß for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion. Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as well as histopathology.
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Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/patologia , Receptores do Ácido Retinoico/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/virologia , Medição de Risco , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Accurate prediction of mastectomy skin flap viability is vital as necrosis causes significant morbidity, potentially compromising results and delaying oncological management. Traditionally assessed by clinical judgement, a more objective evaluation can be provided using intraoperative imaging modalities. This systematic review aimed to compare all intraoperative techniques for assessment of mastectomy flap viability. METHODS: A systematic literature review was performed using MEDLINE and Embase databases. Primary outcomes reported included specificity, sensitivity and predictive values of each test, and mean rates of mastectomy flap necrosis and reoperation. Secondary outcomes included cost analysis. RESULTS: Some 18 studies were included. Designs were prospective cohort study (8), retrospective case series (4), prospective case series (3), retrospective case-control study (1), prospective pilot trial (1) and cost analysis study (1). The studies compared indocyanine green angiography (ICGA) (16 studies) and fluorescein dye angiography (FA) (3 studies) with clinical judgement. Sensitivity and specificity were highest for ICGA (5 studies) ranging from 38 to 100 and 68 to 91 per cent respectively. Both methods overpredicted necrosis. Mean rates of flap necrosis and reoperation decreased with ICGA (7·9 and 5·5 per cent respectively) and FA (3 and 0 per cent) compared with clinical judgement (19·4 and 12·9 per cent). Two studies were designed to define numerical parameters corresponding to perfusion using intraoperative techniques. Two studies performed a cost analysis for ICGA; one claimed a cost benefit and the other advocated its use in high-risk patients only. CONCLUSION: ICGA and FA are potentially useful tools for mastectomy flap assessment. However, the predictive accuracy is subject to the specific settings and model of equipment used. Current recommendations support their use in high-risk patients.
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Management of viral diseases relies on definite and sensitive detection methods. Citrus yellow mosaic virus (CYMV), a double stranded DNA virus of the genus Badnavirus, causes yellow mosaic disease in citrus plants. CYMV is transmitted through budwood and requires a robust and simplified indexing protocol for budwood certification programme. The present study reports development and standardization of an isothermal based recombinase polymerase amplification (RPA) assay for a sensitive, rapid, easy, and cost-effective method for detection and diagnosis of CYMV. Two different oligonucleotide primer sets were designed from ORF III (coding for polyprotein) and ORF II (coding for virion associated protein) regions of CYMV to perform amplification assays. Comparative evaluation of RPA, PCR and immuno-capture recombinase polymerase amplification (IC-RPA) based assays were done using purified DNA and plant crude sap. CYMV infection was efficiently detected from the crude sap in RPA and IC-RPA assays. The primer set used in RPA was specific and did not show any cross-amplification with banana streak MY virus (BSMYV), another Badnavirus species. The results from the present study indicated that RPA assay can be used easily in routine indexing of citrus planting material. To the best of our knowledge, this is the first report on development of a rapid and simplified isothermal detection assay for CYMV and can be utilized as an effective technique in quarantine and budwood certification process.
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Citrus/virologia , Vírus do Mosaico/isolamento & purificação , Doenças das Plantas/virologia , Recombinases/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The present study was undertaken to determine the mechanism of antibacterial activity of a polyphenolic fraction, composed of mainly catechin and isorhamnetin, previously isolated from Kombucha, a 14-day fermented beverage of sugared black tea, against the enteropathogen Vibrio cholerae N16961. Bacterial growth was found to be seriously impaired by the polyphenolic fraction in a dose-dependent manner. Scanning Electron Microscopy demonstrated morphological alterations in bacterial cells when exposed to the polyphenolic fraction in a concentration-dependent manner. Permeabilization assays confirmed that the fraction disrupted bacterial membrane integrity in both time- and dose-dependent manners, which were proportional to the production of intracellular reactive oxygen species (ROS). Furthermore, each of the polyphenols catechin and isorhamnetin showed the ability to permeate bacterial cell membranes by generating oxidative stress, thereby suggesting their role in the antibacterial potential of Kombucha. Thus, the basic mechanism of antibacterial activity of the Kombucha polyphenolic fraction against V. cholerae involved bacterial membrane permeabilization and morphological changes, which might be due to the generation of intracellular ROS. To the best of our knowledge, this is the first report on the investigation of antibacterial mechanism of Kombucha, which is mostly attributed to its polyphenolic content. SIGNIFICANCE AND IMPACT OF THE STUDY: The emergence of multidrug-resistant Vibrio cholerae strains has hindered an efficient anti-Vibrio therapy. This study has demonstrated the membrane damage-mediated antibacterial mechanism of Kombucha, a popular fermented beverage of sugared tea, which is mostly attributed to its polyphenolic content. This study also implies the exploitation of Kombucha as a potential new source of bioactive polyphenols against V. cholerae.
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Antibacterianos/farmacologia , Catequina/farmacologia , Chá de Kombucha/análise , Polifenóis/farmacologia , Quercetina/análogos & derivados , Vibrio cholerae/efeitos dos fármacos , Camellia sinensis/química , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Fermentação , Estresse Oxidativo , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Chá , Vibrio cholerae/crescimento & desenvolvimentoRESUMO
This study was designed to explore the cyproterone acetate (CPA)-induced andrological hypofunction and its correction by oral administration of lycopene. In this concern, spermatogenic, biochemical, histological and genomic profiles were studied. Cyproterone acetate administration for 1 month helped to develop infertile model rats. A significant recovery was noted in sperm motility, sperm count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities of testicular ∆5 , 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, catalase (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD), malondialdehyde (MDA), testicular cholesterol and serum testosterone after the administration of lycopene at 1.5 mg/0.5 ml Tween-80/100 g body weight/day for last 1 month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl-2, caspase-3, ∆5 , 3ß-HSD and 17ß-HSD genes in testicular tissue showed a significant rectification towards the control in CPA-pre-treated cum CPA-lycopene-cotreated rats. Side-by-side histological and histometric studies showed a significant correction in qualitative analysis of spermatogenesis and seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated rats. Lycopene showed outstanding efficacy in the management of CPA-induced testicular hypofunction with special reference to correction in oxidative stress-induced testicular apoptosis at genomic level.
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Carotenoides/farmacologia , Acetato de Ciproterona/farmacologia , Suplementos Nutricionais , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Genômica , Licopeno , Masculino , Malondialdeído/metabolismo , Ratos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismoRESUMO
AIMS: We aimed to determine the effectiveness of CK19 mRNA copy number and tumour related factors in predicting non-sentinel axillary nodal involvement, in order to facilitate the formulation of local treatment guidelines for axillary clearance (ANC) following intra-operative analysis of the sentinel node biopsy (SNB) using one-step nucleic acid amplification (OSNA). METHODS: Patients due to have (SNB) at our institution for breast cancer as well as patients with high grade ductal carcinoma in situ with pre-operative negative assessment of the axilla were included. Alternate slices of each node were sent for assessment by either OSNA or histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA nodal copy number, the total tumour load (TTL) measured by summation of mRNA copy numbers of all positive nodes, the nodal status at ANC and tumour characteristics for each patient were recorded. A model of risk probability was constructed using TTL and tumour related factors. RESULTS: 664 nodes were analysed from 425 patients who had SNB performed between 2011 and 2014. ANC was performed on 105 of these patients. The concordance between OSNA and histology was 91.4% and negative predictive value (NPV) was 97%. TTL (p = 0.003) and LVI (p = 0.04) were identified as risk factors for non-sentinel nodal involvement. The risk probability model identified all patients with pN2 disease for ANC. CONCLUSION: In the future a decision to perform ANC will be based on a risk stratification model based on TTL and tumour related factors.
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Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/cirurgia , Técnicas de Amplificação de Ácido Nucleico , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , RNA Mensageiro/genética , Biópsia de Linfonodo SentinelaRESUMO
Precursor-B-cell receptor (pre-BCR) signaling and spleen tyrosine kinase (SYK) recently were introduced as therapeutic targets for patients with B-cell acute lymphoblastic leukemia (B-ALL), but the importance of this pathway in B-ALL subsets and mechanism of downstream signaling have not fully been elucidated. Here, we provide new detailed insight into the mechanism of pre-BCR signaling in B-ALL. We compared the effects of pharmacological and genetic disruption of pre-BCR signaling in vitro and in mouse models for B-ALL, demonstrating exquisite dependency of pre-BCR(+) B-ALL, but not other B-ALL subsets, on this signaling pathway. We demonstrate that SYK, PI3K/AKT, FOXO1 and MYC are important downstream mediators of pre-BCR signaling in B-ALL. Furthermore, we define a characteristic immune phenotype and gene expression signature of pre-BCR(+) ALL to distinguish them from other B-ALL subsets. These data provide comprehensive new insight into pre-BCR signaling in B-ALL and corroborate pre-BCR signaling and SYK as promising new therapeutic targets in pre-BCR(+) B-ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Células Precursoras de Linfócitos B/química , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Proteína Forkhead Box O1/metabolismo , Xenoenxertos , Humanos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Quinase Syk/metabolismoRESUMO
New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.
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DNA/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Preparações Farmacêuticas/administração & dosagem , DNA/química , Concentração de Íons de Hidrogênio , Micelas , Preparações Farmacêuticas/químicaRESUMO
Ba-La-tellurite glasses doped with Yb(3+) ions have been prepared through melt quenching technique by modifying their composition with the inclusion of varied concentration of Al2O3 to elucidate its effects on glass structural, elastic, thermal properties and Yb(3+) ion NIR luminescence performance. The FTIR spectral analysis indicates Al2O3 addition is promoting the conversion of BOs from NBOs which have been generated during the process of depolymerisation of main glass forming TeO4 units. The elastic properties of the glass revealed an improved rigidity of the glass network on addition of Al2O3. In concurrence to this, differential thermal analysis showed an increase in glass transition temperature with improved thermal stability factor. Also, Yb(3+) fluorescence dynamics demonstrated that, Al2O3 inclusion helps in restraining the detrimental radiation trapping of â¼1µm emission.
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Óxido de Alumínio/química , Bário/química , Lantânio/química , Telúrio/química , Itérbio/química , Elasticidade , Vidro/química , Luminescência , Radiação , Termodinâmica , Temperatura de TransiçãoRESUMO
The present study was conducted to explore the effect of ethyl acetate fraction of hydro-methanolic (40 : 60) extract of seed of Eugenia jambolana on testicular impairment in diabetic rats. In this respect, biomarkers of oxidative stress, genomics and proteomics in testicular tissue were assessed. Side by side, glycated haemoglobin, serum testosterone, activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum, epididymal sperm count including reproductive organosomatic indices were evaluated. Results indicate that a significant recovery (P < 0.05) in the levels of these parameters in fraction-treated diabetic group in comparison with diabetic control. A significant recovery was noted (P < 0.05) in the expression of Bax and Bcl-2 gene towards the control after the treatment of said fraction. Histological study also focused a significant recovery (P < 0.05) in the number of different generation of germ cells at stage VII of spermatogenesis in fraction-treated diabetic group. The said fraction treatment to diabetic rat can recover the activities of serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase significantly towards the control (P < 0.05). Finally, it may be concluded that ethyl acetate fraction of seed of E. jambolana has a promiseable remedial effect on diabetes-induced testicular dysfunctions in male rat without inducing any metabolic toxicity.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Fitoterapia , Syzygium , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/genética , Frutose/metabolismo , Expressão Gênica/efeitos dos fármacos , Genes bcl-2 , Genômica , Hidroxiesteroide Desidrogenases/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteômica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Glândulas Seminais/efeitos dos fármacos , Glândulas Seminais/metabolismo , Epitélio Seminífero/efeitos dos fármacos , Epitélio Seminífero/patologia , Contagem de Espermatozoides , Testículo/patologia , Testosterona/sangue , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Progesterone is essential for endometrial receptivity in primates. It is now evident that embryo-derived signal influences implantation stage endometrium under progesterone dominance, and collectively results in endometrial receptivity to implanting blastocyst. Previously, a few studies were performed using global gene profiling based on microarray technology to identify changes in gene expression between early luteal phase and mid luteal phase endometrium, however, the issue of combinatorial regulation by progesterone-dependent regulation and by embryo-derived signal on transcripts profiles during endometrial differentiation toward receptivity for blastocyst implantation in primates has not been addressed. the present review summarizes a few issues, specifically that of transforming growth factor ß-tumour necrosis factor α (TGFß-TNFα) pathways and signal transducer and activator of transcription (STAT) signalling system related to luteal phase progesterone action on endometrial receptivity in terms of its transcriptomic expression using a potent antiprogestin (mifepristone) in conception cycles of the rhesus monkey as a non-human primate model.
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Implantação do Embrião/fisiologia , Endométrio/metabolismo , Regulação da Expressão Gênica/fisiologia , Primatas/metabolismo , Progesterona/metabolismo , Transdução de Sinais/fisiologia , Animais , Feminino , Humanos , Gravidez , Fatores de Transcrição STAT/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Granuloma/parasitologia , Lobosea/patogenicidade , Meningoencefalite/parasitologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Pré-Escolar , Granuloma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningoencefalite/patologia , Tomografia Computadorizada por Raios XRESUMO
Blastocyst implantation in the rhesus monkey is inhibited by administration of antibody against vascular endothelial growth factor (VEGF) A during peri-implantation period with no change in the circulatory concentrations of estradiol, progesterone, and VEGF. In this study, we have investigated the effect of administration of a MAB to VEGFA on days 5 and 10 after ovulation upon the mRNA expression, immunopositive protein expression, and immunohistological localization of IGF2, IGF binding protein 1 (IGFBP1) and matrix metalloproteinases (MMPs) 2 and 9 in the implantation-stage endometrium collected on day 13 after ovulation from fecund cycles of rhesus monkeys. The comparison between isotype-matched IgG (control; n=8)- and VEGF antibody (VEGF Mab; n=8)-treated animals revealed higher (P<0.05) IGF2 in lacunar and villous syncytiotrophoblasts, trophoblast cell columns, migrating extravillous trophoblast cells, and endovascular trophoblast cells in control animals, but with no change in the various cell types of maternal endometrium between the two groups. No change in IGFBP1 expression in the endometrium was observed between the two groups. MMPs 2 and 9 were detected in syncytiotrophoblast in lacunae and villi, trophoblast cell columns, and extravillous trophoblast cells in control samples. MMP9 transcript expression in maternal endometrium and its immunopositivity in endometrial stroma and trophoblast cells were lower (P<0.05) with no change in MMP2 level in VEGF Mab-exposed samples compared with those in control samples. A functional network involving VEGF, IGF2, and MMP9 in early placental trophoblast cells and maternal endometrium appears to be important for normal placentation.
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Anticorpos Neutralizantes/farmacologia , Endométrio/efeitos dos fármacos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Macaca mulatta , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Implantação do Embrião/fisiologia , Embrião de Mamíferos/metabolismo , Endométrio/metabolismo , Feminino , Macaca mulatta/imunologia , Macaca mulatta/metabolismo , Placentação/fisiologia , Gravidez , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Trofoblastos/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Aim of the study was to assess prostate motion on daily basis with respect to setup and to compare the shifts based on bony anatomy and gold fiducial markers. MATERIALS AND METHODS: Gold fiducial markers were inserted in prostate under U/S guidance and daily portal images were taken and compared with digitally reconstructed images, both using bony landmarks and fiducial markers as reference. A dose of 2 MU was given for two orthogonal images daily. The mean and standard deviation of displacement using gold seeds and bone were calculated. Systematic and random errors were generated. The planning target volume (PTV) was calculated using the Van Herk formula. RESULTS: A total of 180 portal images from 10 patients were studied. The mean displacement along x, y and z axes was 1.67 mm, 3.58 mm, and 1.76 mm using fiducial markers and 2.12 mm, 3.47 mm, and 2.09 mm using bony landmarks, respectively. The mean internal organ motion was 1.23 mm (+1.45), 3.11 mm (+2.69 mm); and 1.87 mm (+1.67 mm) along x, y and z axes, respectively. The PTV to account for prostate motion if daily matching was not done was 4.64 mm, 10.41 mm and 4.40 mm along lateral, superoinferior, and anteroposterior directions, respectively. If bony landmarks were used for daily matching, margins of 3.61 mm, 7.31 mm, and 4.72 mm in lateral, superoinferior, and anteroposterior directions should be added to the clinical target volume. CONCLUSION: Daily alignment using gold fiducial markers is an effective method of localizing prostate displacement. It provides the option of reducing margins, thus limiting normal tissue toxicity and allowing the possibility of dose escalation for better long-term control.
Assuntos
Ouro/química , Ossos Pélvicos/diagnóstico por imagem , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Próteses e Implantes , Planejamento da Radioterapia Assistida por Computador , Humanos , Masculino , Ossos Pélvicos/anatomia & histologia , Próstata/anatomia & histologia , Neoplasias da Próstata/radioterapia , Intensificação de Imagem RadiográficaRESUMO
Early placental development is critical for successful pregnancy. Recently, we have reported that -70 genes were differentially expressed in human placental villi between 6- and 8- weeks of gestation in cDNA-based expression arrays for -400 PCR products, of which six specific gene products (COL4A4, CXCR4, ERBB2, HDAC1, HPRT1, and TNFRSF1A) appeared intriguing. In the present study we have examined expressions of these six candidate genes in placental villi obtained from 6-weeks, 7-weeks and 8-weeks (n = 6 for each group) human placental samples using quantitative real time RTPCR. We observed that there was considerable concordance (>95% confidence) in pair-wise analysis of transcript profiles between the two methods, however, absolute quantitative values as measured by quantitative RTPCR differed from those obtained from cDNA-based array analysis for 2 gene products (CXCR4 and ERBB2) out of 6 genes. No significant change was observed in the steady state expression of COL4A4 and HPRT1 during the time period examined. However, there was significant decrease in CXCR4 for 7-weeks (P < 0.01) and 8-weeks (P < 0.05) samples, and significant (P < 0.05) increase was seen for ERBB2 in 7-weeks and 8-weeks as compared to 6-weeks samples with no change between 7-weeks and 8-weeks samples. Moreover, significant (P < 0.05) increase for HDAC1 and decrease for TNFRSF1A was observed in 8-weeks samples as compared to 6-weeks samples with no change observed between 6-weeks and 7-weeks samples. We infer that it is essential that cDNA array-based data are verified in terms of quantitative estimates preferably by quantitative PCR before their use for any exploratory purpose. Taking together our previous array based data and the present study we conclude that a categorical balance exists between the expression of ERBB2 and HDAC1 genes affecting cell proliferation and differentiation in one hand, and CXCR4 and TNFRSF1A affecting chemotaxis, inflammatory response and apoptosis on the other hand. The expression of these genes appear important for the early development of human placental villi.