Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 87
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Med J Armed Forces India ; 80(3): 353-358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799998

RESUMO

Background: Poor accessibility of health care facilities is a major barrier for differently abled people when seeking health care. Yet, accessibility is rarely audited. This study reports findings from the first assessment of the accessibility in a health care institution of national importance. This study also assumes importance from various laws and legislation that assure equality and rights for people with disabilities (PWDs). Keeping the objectives in mind, this study was performed with an aim to study the situational analysis of the health institution of national importance for assessing the compliance of hospital premises for being disabled friendly, to find any lacunae, and to suggest remedial measures based on the study finding. The aim was to conduct a content and quality review of research into the hospital experiences of PWD and to identify gaps. Methods: This was a hospital-based cross sectional study done in a period of 30 days. The gap analysis was performed with validated checklist provided by Central Public Works Department, Government of India (CPWD). Results: Out of total 126 pointers, 45 pointers were found to be totally compliant, 30 pointers were found to be partially compliant, and remaining 51 pointers were found to be not applicable to the hospitals. Conclusion: This assessment of the accessibility of health care facilities showed that that it is feasible to undertake these audits on a large scale, and these audits should be repeated in other settings. It highlights important gaps in accessibility, increasing the risk of the violation of the right to health of PWDs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35722445

RESUMO

Background: The Medical Record (MR) contains the information which is needed to plan, provide, and evaluate the care given to the individual. It also serves as a pivotal tool for communicating information to all the health personnel who manage the patient, and it contributes to the continuity of patient care. There is an unmet need of identifying and correcting the issues faced with MR and Medical Records Departments (MRDs) so that higher efficiency can be achieved. This study was conducted to study the deficiencies and discrepancies found in MRD files during COVID management and to correlate the deficiencies with the facilities available and the workflow. Later Lean Management (LM) was applied to ensure compliance and efficiency in the system. Methods: An observational study was done on the audit of COVID 19 patient files and facilities in the care centres. Process mapping was done. The data for LM were collected by brainstorming, observation, interview, and workflow review of several processes, values, number of wastes, and suggestions were documented the MRD staff. Results: Area available was 400 m2 which is adequate against the norm of 350 m2. The existing staff of 30 was adequate as per norms. Deficiencies were observed in physical examination, history, radiology, and laboratory reports. The findings showed that the MRD units had 13 current processes, 26 wastes, and 10 values were identified. In addition, they were offered a total of 25 comments on eliminating the waste. Conclusion: Staff and equipment were adequate. Recommendations include regular staff training and usage of electronic medical records, focus on deficiency check by specific MRD staff on regular basis monitored by the administration and supported by the medical audit committee. The study also recommends that suggestions applied after LM should be implemented in letter and spirit and a repeat study of LM is advisable after regular intervals to maintain the quality standards and to maintain or further improve the efficiency.

3.
Med J Armed Forces India ; 75(2): 211-215, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31065192

RESUMO

BACKGROUND: Violence against health-care workers has become a great issue in health-care organizations. This study was conceptualized with the aim to know the prevalence of violence and to identify gap between rate of reporting of an incident of violence at a tertiary care hospital in India. METHODS: The study was descriptive and cross-sectional; a validated questionnaire was used as a tool. Reported incidents of violence against workers were collected. P value <0.05 was considered statistically significant in the analysis. A Z test for proportion at 95% confidence interval was applied to analyze the level of difference between prevalence, rate of reporting, and their level of awareness. RESULTS: Of 394 respondents, 136(34.5%) workers had experienced workplace violence in the last 12 months. It was found that total 32 incidents of workplace violence were reported to the concerned authority. The reporting rate of violence is significantly low (23.5%), in spite of high prevalence (34.5%). Level of awareness regarding the reporting mechanism and regulations for the safeguard of health-care workers against workplace violence is only 24.6 %. CONCLUSION: This study concluded that the prevalence of violence among health-care workers is quite high, but the reporting rate is significantly low. The low rate of reporting is because of lack of awareness about the reporting mechanism of workplace violence. It is recommended that sensitizing workshops should be conducted to increase the level of awareness, which will result in reduction in the prevalence of violence and building a safe and secured workplace for health-care providers.

4.
Org Biomol Chem ; 16(5): 698-702, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29319101

RESUMO

Selective androgen receptor modulators (SARMs) are a class of androgen receptor drugs, which have a high potential to be performance enhancers in human and animal sports. Arylpropionamides are one of the major SARM classes and get rapidly metabolized significantly complicating simple detection of misconduct in blood or urine sample analysis. Specific drug-derived metabolites are required as references due to a short half-life of the parent compound but are generally lacking. The difficulty in metabolism studies is the determination of the correct regio and stereoselectivity during metabolic conversion processes. In this study, we have elucidated and verified the chemical structure of two major equine arylpropionamide-based SARM metabolites using a combination of chemical synthesis and liquid chromatography-mass spectrometry (LC-MS) analysis. These synthesized SARM-derived metabolites can readily be utilized as reference standards for routine mass spectrometry-based doping control analysis of at least three commonly used performance-enhancing drugs to unambigously identify misconduct.


Assuntos
Acetamidas/metabolismo , Amidas/metabolismo , Aminofenóis/metabolismo , Anabolizantes/metabolismo , Anilidas/metabolismo , Receptores Androgênicos/metabolismo , Acetamidas/química , Acetamidas/urina , Amidas/química , Amidas/urina , Aminofenóis/química , Aminofenóis/urina , Anabolizantes/química , Anabolizantes/urina , Anilidas/química , Anilidas/urina , Animais , Cromatografia Líquida de Alta Pressão/métodos , Dopagem Esportivo , Cavalos , Humanos , Espectrometria de Massas/métodos , Detecção do Abuso de Substâncias/métodos
5.
Int Orthop ; 42(5): 1143-1147, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29289987

RESUMO

AIMS: We present the largest series of paediatric pelvic pyomyositis from a temperate country, analyse the factors influencing long term prognosis and suggest a diagnostic protocol. MATERIALS AND METHOD: We included 41 patients diagnosed with primary paediatric pelvic pyomyositis between 1998 and 2016, in this study with a mean age of 7.5 years. Demographic, clinical, radiological and follow-up data were reviewed. Statistical analysis was performed to analyse the influence of early diagnosis and treatment on the final outcome. RESULTS: There was an increased occurrence of primary pelvic pyomyositis in the last two years. Of cases identified, 85% fulfilled Kocher's criteria for hip septic arthritis. The mean time to diagnosis was 2.8 ± 0.8 days. The most common muscle affected was obturator internus (65.85%) and multifocal involvement was common (46.34%). Early diagnosis and antibiotic treatment within seven days from the time of onset of symptoms was the only factor that influenced final outcome (p < 0.001). DISCUSSION AND CONCLUSION: Pyomyositis is no longer restricted to tropical countries. The time from onset of symptoms to start of antibiotic treatment influences the final outcome. Clinical examination and inflammatory markers have low specificity in distinguishing between pyomyositis, septic arthritis, osteomyelitis or other infections. MRI is more sensitive and can diagnose pyomyositis in its early stages. Every suspected case of septic arthritis of the hip should undergo an ultrasound. MRI scan may be performed if the ultrasound shows inconclusive evidence of an effusion. Early identification will facilitate early antibiotic treatment which will improve the final outcome. CLINICAL RELEVANCE: There is an increasing occurrence of this tropical disease in temperate countries. Early diagnosis with an MRI scan and early antibiotic use results in good outcomes.


Assuntos
Músculo Esquelético/patologia , Pelve/patologia , Piomiosite/epidemiologia , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Músculo Esquelético/microbiologia , Prognóstico , Estudos Prospectivos , Piomiosite/diagnóstico , Piomiosite/terapia , Reino Unido/epidemiologia
6.
Chin J Traumatol ; 21(1): 34-37, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29402719

RESUMO

PURPOSE: The aim of this study is to discuss the results of different intramedullary devices used in the management of paediatric radial neck fractures and to suggest methods to avoid the pitfalls of the technique. METHODS: Thirty patients with isolated Judet III and IV fractures were included in this prospective study. Judet I and II fractures and radial neck fractures associated with other injuries were excluded. The final results were graded using the Metaizeau functional scoring system and Oxford Elbow Score. RESULTS: The functional result was good to excellent in 24 of 30 cases (80%). The mean Oxford Elbow Score was 44.32. The mean follow-up was 40.11 months. The complications seen were radiocapitellar joint penetration - 6 cases at mean 4.87 weeks, redisplacement - 6, radial epiphyseal sclerosis - 5, and heterotopic ossification - 1 case. CONCLUSION: Intramedullary K wires may result in radiocapitellar joint penetration. Titanium Elastic Nail System should not be used as purely fixation devices as they may not prevent redisplacement. Regular follow-up until at least 6 weeks is essential. Patients who have a Judet IV fracture and need open reduction should be given a guarded prognosis. The paper highlights the pitfalls of the technique and makes recommendations regarding the type of implant, follow-up and patient counselling in Judet IV fractures.


Assuntos
Fios Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Rádio/cirurgia , Criança , Pré-Escolar , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Masculino , Estudos Prospectivos
7.
Angew Chem Int Ed Engl ; 57(42): 13805-13809, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30168889

RESUMO

While metabolites derived from gut microbiota metabolism have been linked to disease development in the human host, the chemical tools required for their detailed analysis and the discovery of biomarkers are limited. A unique and multifunctional chemical probe for mass spectrometric analysis, which contains p-nitrocinnamyloxycarbonyl as a new bioorthogonal cleavage site has been designed and synthesized. Coupled to magnetic beads, this chemical probe allows for straightforward extraction of metabolites from human samples and release under mild conditions. This isolation from the sample matrix results in significantly reduced ion suppression, an increased mass spectrometric sensitivity, and facilitates the detection of metabolites in femtomole quantities. The chemoselective probe was applied to the analysis of human fecal samples, resulting in the discovery of four metabolites previously unreported in this sample type and confirmation of the presence of medically relevant gut microbiota-derived metabolites.


Assuntos
Microbioma Gastrointestinal , Sondas Moleculares/química , Cromatografia Líquida/métodos , Humanos , Magnetismo , Espectrometria de Massas/métodos
8.
Mol Pharm ; 14(6): 1883-1897, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28402673

RESUMO

The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL was calculated as 85-90% and 10-12%, respectively. The coumarin-6 LPHNP formulations showed rapid internalization within 2 h incubation with MCF-7 and MDA-MB-231 cells. With 8-10 times, greater bioavailability of drug-loaded LPHNPs than free MTX and ACL was obtained. Also, antitumor efficacy of MTX- and ACL-loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse model. This model showed better control over tumor growth with MTX- and ACL-loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs showed prophylactic and anticancer activity in DMBA-induced mouse model at higher dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when administered in combination with MTX. In conclusion, ACL enhances the therapeutic and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs, as confirmed by cell viability and serum angiogenesis (IL-6, TNF-α, IL-1ß, COX2, and MMP1) at both transcript and proteome level.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Diclofenaco/análogos & derivados , Lipídeos/química , Metotrexato/administração & dosagem , Metotrexato/farmacocinética , Nanopartículas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Diclofenaco/administração & dosagem , Diclofenaco/química , Diclofenaco/farmacocinética , Diclofenaco/farmacologia , Feminino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Células MCF-7 , Metaloproteinase 1 da Matriz/metabolismo , Metotrexato/química , Metotrexato/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismo
9.
Nanomedicine ; 12(7): 2043-2060, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27234306

RESUMO

The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ligantes , Neoplasias Mamárias Experimentais/tratamento farmacológico , Metotrexato/administração & dosagem , Animais , Apoptose , Sobrevivência Celular , Humanos
10.
Drug Dev Ind Pharm ; 42(6): 897-905, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26577703

RESUMO

The present study documents the fabrication and characterization of a topically applicable gel loaded with nanostructured lipid carriers (NLCs) of adapalene (ADA) and vitamin C (ascorbyl-6-palmitate [AP]). The NLCs were prepared by high pressure homogenization (HPH) method followed by incorporation into AP loaded gel. The fabricated system was characterized for size, poly dispersity index, entrapment efficiency (EE) and in vitro drug release properties, and was further investigated for skin compliance, skin transport characteristics (skin permeation and bio-distribution), rheological behavior, texture profile analysis and anti-acne therapeutic potential against testosterone-induced acne in male Wistar rats. The NLC-based formulation improved targeting of the skin epidermal layer and reducing systemic penetration. The co-administration of vitamin C led to an adjunct effect in acne therapy in physiological conditions. In brief, the present results suggest the potential of NLCs as a novel carrier for the dermal delivery of ADA and also the synergistic effect of vitamin C in topical therapeutics.


Assuntos
Acne Vulgar/tratamento farmacológico , Adapaleno/administração & dosagem , Ácido Ascórbico/administração & dosagem , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/administração & dosagem , Adapaleno/química , Administração Cutânea , Animais , Ácido Ascórbico/química , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Géis/administração & dosagem , Géis/química , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanoestruturas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Absorção Cutânea
11.
Transfus Apher Sci ; 50(3): 415-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24797241

RESUMO

OBJECTIVES: To evaluate the prevalence of the anti-red blood cell antibodies among healthy blood donors. MATERIAL AND METHODS: Antibody screening of all voluntary blood donor serum was performed as routine immunohematological procedure. Positive sera were further investigated to identify the specificity of irregular erythrocyte antibody by commercially available red cell panel (ID-Dia Panel, Diamed-ID Microtyping System). RESULT: A total of 47,450 donors were screened for the presence of irregular erythrocyte antibodies. A total of forty-six donors showed presence of alloantibodies in their serum (46/47,450%, 0.09%), yielding a prevalence of 0.09%. Most frequent alloantibodies identified were of MNS blood group system. The results showed statistically a higher prevalence of RBC alloantibodies in females than in males. CONCLUSION: Screening for presence of alloantibodies in donor blood is important to provide compatible blood products and to avoid transfusion reactions.


Assuntos
Doadores de Sangue , Antígenos de Grupos Sanguíneos/sangue , Seleção do Doador , Isoanticorpos/sangue , Adolescente , Adulto , Antígenos de Grupos Sanguíneos/imunologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Feminino , Humanos , Índia , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
12.
Transfus Apher Sci ; 50(1): 75-80, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24314713

RESUMO

BACKGROUND: Regional Blood Transfusion Centre (RBTC), GTB Hospital, Delhi is providing safe and quality blood to one third of Delhi population. A discrepancy exists when reactions in forward grouping do not match with reverse grouping or if the previous and current results do not match. AIM: To analyze ABO blood group discrepancies in an algorithmic manner, and to access the incidence and causes of ABO discrepancies among blood donors. MATERIAL AND METHODS: Retrospective data of blood donors with blood group discrepancies was recorded in Regional Blood Transfusion Centre (East) Delhi, during a period of 3years from January 2010 to May 2013. DiaMed-ID Card Micro Typing System using Gel Cards (Cressier sur Morat, Switzerland) were used for determination of the ABO/Rh blood groups combined with reverse grouping. A detailed serological workup of these cases was studied for recognition and resolution of the blood group discrepancy. RESULTS: Total number of donors during the study period were 104,010 (30,120; 31,117; 32,173 and 10,600 respectively). Blood group discrepancies were found in 51 cases (0.04%). There were 30 (58.8%) cases with low avidity anti-B Antibodies, 10 (19.6%) cases with weaker expression or subgroups of A, 2 (3.9%) cases with weaker expression or subgroups of B, 5(9.8%) cases with unexpected alloantibodies (Anti-N and Anti-M, Anti-Lea) and one(1.9%) case of Bombay blood group. In 3 cases, discrepancy could not be resolved and were referred to reference laboratory for confirmation by molecular analysis. The most frequent cause of discrepancy in forward grouping was found to be weak A or B antigen expressions and in reverse grouping decreased anti-B titers was most common. CONCLUSION: All discrepancies reported on ABO cell and serum grouping must be investigated further, so that correct blood group is reported, minimizing the chances of transfusion reaction. A note of caution should be mentioned on the blood group card to prevent ABO incompatibility in case of transfusion.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Doadores de Sangue , Transfusão de Sangue/métodos , Algoritmos , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Tipagem e Reações Cruzadas Sanguíneas , Humanos , Índia , Isoanticorpos/sangue , Erros Médicos , Estudos Retrospectivos
13.
Adv Drug Deliv Rev ; 205: 115174, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38161056

RESUMO

Onychomycosis continues to be the most challenging disease condition for pharmaceutical scientists to develop an effective drug delivery system. Treatment challenges lie in incomplete cure and high relapse rate. Present compilation provides cumulative information on pathophysiology, diagnostic techniques, and conventional treatment strategies to manage onychomycosis. Novel technologies developed for successful delivery of antifungal molecules are also discussed in brief. Multidirectional information offered by this article also unlocks the panoramic view of leading patented technologies and clinical trials. The obtained clinical landscape recommends the use of advanced technology driven approaches, as a promising way-out for treatment of onychomycosis. Collectively, present review warrants the application of novel technologies for the successful management of onychomycosis. This review will assist readers to envision a better understanding about the technologies available for combating onychomycosis. We also trust that these contributions address and certainly will encourage the design and development of nanocarriers-based delivery vehicles for effective management of onychomycosis.


Assuntos
Onicomicose , Humanos , Onicomicose/diagnóstico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Administração Tópica , Antifúngicos/uso terapêutico , Sistemas de Liberação de Medicamentos
14.
Int J Nanomedicine ; 19: 2149-2177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482519

RESUMO

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Diclofenaco/análogos & derivados , Nanopartículas , Humanos , Ratos , Animais , Metotrexato , Ratos Wistar , Artrite Reumatoide/patologia , Nanopartículas/química , Inflamação/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Lipídeos/química
16.
Biomed Res Int ; 2022: 1012684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832854

RESUMO

Microsatellites are small, repetitive sequences found all across the human genome. Microsatellite instability is the phenomenon of variations in the length of microsatellites induced by the insertion or deletion of repeat units in tumor tissue (MSI). MSI-type stomach malignancy has distinct genetic phenotypes and clinic pathological characteristics, and the stability of microsatellites influences whether or not patients with gastric mesothelioma react to immunotherapy. As a result, determining MSI status prior to surgery is critical for developing treatment options for individuals with gastric cancer. Traditional MSI detection approaches need immunological histochemistry and genetic analysis, which adds to the expense and makes it difficult to apply to every patient in clinical practice. In this study, to predict the MSI status of gastric cancer patients, researchers used image feature extraction technology and a machine learning algorithm to evaluate high-resolution histopathology pictures of patients. 279 cases of raw data were obtained from the TCGA database, 442 samples were obtained after preprocessing and upsampling, and 445 quantitative image features, including first-order statistics of impressions, texture features, and wavelet features, were extracted from the histopathological images of each sample. To filter the characteristics and provide a prediction label (risk score) for MSI status of gastric cancer, Lasso regression was utilized. The predictive label's classification performance was evaluated using a logistic classification model, which was then coupled with the clinical data of each patient to create a customized nomogram for MSI status prediction using multivariate analysis.


Assuntos
Mesotelioma Maligno , Neoplasias Gástricas , Humanos , Instabilidade de Microssatélites , Repetições de Microssatélites , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
17.
Nat Cancer ; 3(2): 156-172, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35228749

RESUMO

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.


Assuntos
Aminoidrolases , Leucemia Mieloide Aguda , Aminoidrolases/genética , Humanos , Hidrolases , Leucemia Mieloide Aguda/tratamento farmacológico , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Enzimas Multifuncionais/genética , Timidina
18.
Proc Natl Acad Sci U S A ; 105(2): 663-7, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18160532

RESUMO

Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.


Assuntos
Anilidas/farmacologia , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Coração/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Adolescente , Adulto , Anilidas/química , Método Duplo-Cego , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Placebos , Fatores de Risco , Tiazolidinedionas/farmacologia
19.
Front Pharmacol ; 12: 713616, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616297

RESUMO

Aceclofenac (ACE), a cyclooxygenase-2 inhibitor, is the derivative of the diclofenac group that has been in use for the symptomatic treatment of systemic inflammatory autoimmune disease, rheumatoid arthritis (RA). Partial solubility, high lipophilic nature, and stability challenge its use in developing topical formulations. Hence, we developed and characterized nanostructured lipid carrier (NLC)-based ACE (ACE-NLC) hydrogel for an efficient transdermal delivery. NLC microemulsion was prepared using different lipids by various methods and was characterized with respect to particle size, zeta potential, surface morphology, and drug encapsulation efficiency. The optimized NLC formulation was incorporated into Carbopol® 940 gel, and this arrangement was characterized and compared with the existing marketed gel (Mkt-gel) formulation to assess in vitro drug release, rheology, texture profile, in vivo skin retention and permeation, and stability. Furthermore, prepared and characterized ACE-loaded NLC formulation was evaluated for skin integrity and fitted in a dermatokinetic model. The results of this study confirmed the spherical shape; smooth morphology and nanometric size attested by Zetasizer and scanning and transmission electron microcopy; and stability of the ACE-NLC formulation. The ACE-NLC-gel formulation showed good rheological and texture characteristics, and better skin distribution in the epidermis and dermis. Moreover, ACE-NLC permeated deeper in the skin layers and kept the skin integrity intact. Overall, NLC-based gel formulation of ACE might be a promising nanoscale lipid carrier for topical application when compared with the conventional Mkt-gel formulation.

20.
Asian J Neurosurg ; 16(3): 623-625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660383

RESUMO

Primary CNS lymphoma (PCNSL) is rare malignant B cell lymphoid tumor of brain which predominantly occurs in supratentorial region in periventricular location. Majority of PCNSL are of DLBCL type and idiopathic in etiology. Here we are reporting a case of primary CNS lymphoma, DLBCL involving extremely uncommon intraventricular location. Central neurocytoma, subependymal giant cell astrocytoma, choroid plexus tumors and meningiomas are the common diagnosis at this site. Aim of reporting this case is to bring awareness of unusual intraventricular location of primary CNS lymphoma which should be kept in mind before considering gross total excision of lesion.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA