Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Immunol Invest ; 53(3): 295-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38206610

RESUMO

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.


Assuntos
Nanopartículas , Doenças Respiratórias , Idoso , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Imunomodulação , Pulmão
2.
Cell Mol Neurobiol ; 43(6): 2491-2523, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36847930

RESUMO

The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Proteínas tau , Diagnóstico Precoce , Biomarcadores
3.
Arch Pharm (Weinheim) ; 351(3-4): e1700349, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29522645

RESUMO

A series of 2-oxo-2-phenylethylidene linked 2-oxo-benzo[1,4]oxazine analogues 17a-x and 18a-o, incorporated with a variety of electron-withdrawing as well as electron-donating groups at ring A and ring C, were synthesized under greener conditions in excellent yields (up to 98%). These analogues 17a-x and 18a-o were evaluated for their arachidonic acid (AA)-induced platelet aggregation inhibitory activities in comparison with the standard reference aspirin (IC50 = 21.34 ± 1.09 µg/mL). Among all the screened compounds, eight analogues, 17i, 17x, 18f, 18g, 18h, 18i, 18l, and 18o, were identified as promising platelet aggregation inhibitors as compared to aspirin. In addition, cytotoxic studies in 3T3 fibroblast cell lines by MTT assay of the promising compounds (17i, 17x, 18f-18i, 18l, and 18o) were also performed and the compounds were found to be non-toxic in nature. Furthermore, the results on the AA-induced platelet aggregation inhibitory activities of these compounds (17i, 17x, 18f-18i, 18l, and 18o) were validated via in silico molecular docking simulation studies. To the best of our knowledge, this is the first report of the identification of non-peptide-based functionalized 2-oxo-benzo[1,4]oxazines as platelet aggregation inhibitors.


Assuntos
Benzoxazinas/farmacologia , Desenho de Fármacos , Simulação de Acoplamento Molecular , Oxazinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Células 3T3 , Animais , Benzoxazinas/síntese química , Benzoxazinas/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Oxazinas/síntese química , Oxazinas/química , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Relação Estrutura-Atividade
4.
Bioorg Med Chem Lett ; 27(18): 4288-4293, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28838699

RESUMO

This study reports the simultaneous delivery of EGFP siRNA and the chemotherapeutic drug, doxorubicin by means of the composition that results from the electrostatic interaction between positively charged siRNA-complexes of gold nanoparticles (AuNPs) capped with PEI, 25kDa (P25-AuNPs) and negatively charged carboxymethyl cellulose formulated PLGA nanoparticles loaded with doxorubicin. The nanoparticles and their facile interaction were studied by means of dynamic light scattering (DLS), zeta potential, transmission electron microscopic (TEM) measurements. The flow cytometric and confocal microscopic analysis evidenced the simultaneous internalization of both labelled siRNA and doxorubin into around 55% of the HeLa cancer cell population. Fluorescence microscopic studies enabled the visual analysis of EGFP expressing HeLa cells which suggested that the composition mediated codelivery resulted in a substantial downregulation of EGFP expression and intracellular accumulation of doxorubicin. Interestingly, codelivery treatment resulted in an increased cellular delivery of doxorubicin when compared to PLGA-DOX alone treatment. On the other hand, the activity of siRNA complexes of PEI-AuNPs was completely retained even when they were part of composition. The results suggest that this formulation can serve as promising tool for delivery applications in combinatorial anticancer therapy.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Ouro/química , Ácido Láctico/química , Nanopartículas Metálicas/química , Polietilenoimina/química , Ácido Poliglicólico/química , RNA Interferente Pequeno/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Fluorescência Verde/química , Células HeLa , Humanos , Estrutura Molecular , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , RNA Interferente Pequeno/química , Relação Estrutura-Atividade , Propriedades de Superfície
5.
Bioorg Med Chem Lett ; 27(18): 4393-4398, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28835348

RESUMO

A new series of functionalized (Z)-3-(2-oxo-2-substituted ethylidene)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-ones 23-26, incorporating pharmaceutically privileged substructures such as cyclopropyl, naphthyl, biphenyl and cyclohexylphenyl were synthesized in excellent yields. All the synthesized compounds were screened for their in vitro antibacterial activity against gram-(+)ve and gram-(-)ve bacterial species i.e. S. griseus, S. aureus, B. subtillis and E. coli as well as in vitro antifungal activity against fungal species i.e. F. oxysporium, A. niger, P. funiculosum and T. reesei, respectively. In this study, compounds containing cyclopropyl and cyclohexylphenyl substructures were identified as promising antimicrobial agents than standard drugs, ampicillin and chloramphenicol as well as ketoconazole. SAR study illustrates that electron-withdrawing groups increases the antibacterial as well as antifungal activity of 2-oxo-benzo[1,4]oxazines and vice versa. Compounds 23e and 26e, the most active compounds of the series, displayed promising antibacterial activity than Ampicillin and Chloramphenicol. Moreover, compound 26d showed promising antifungal potency as compared to Ketoconazole. Cytotoxic studies of the active compounds i.e. 23c-e, 24e, 25d and 26d-e found to be non-toxic in nature in 3T3 fibroblast cell lines using MTT assay.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Benzoxazinas/farmacologia , Fungos/efeitos dos fármacos , Células 3T3 , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Benzoxazinas/síntese química , Benzoxazinas/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
6.
Acta Chim Slov ; 64(4): 988-1004, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29318312

RESUMO

A microwave-assisted, environmentally benign green protocol for the synthesis of functionalized (Z)-3-(2-oxo-2-phenylethylidene)-3, 4-dihydro-2H-benzo[b][1,4]oxazin-2-ones (11a-n) in excellent yields (upto 97%) and (Z)-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-ones (14a-h) (upto 96% yield) are reported. The practical applicability of developed methodology were also confirmed by the gram scale synthesis of 11a, 14c and 14e; synthesis of anticancer alkaloid Cephalandole A 16 (89% yield). All the synthesized compounds 11a-n, 14a-h and 16 were assessed for their in vitro antioxidant activities in DPPH radical scavenging and FRAP assay. In DPPH assay, compounds 11a, 14c and 14e, the most active compounds of the series, were found to show IC50 value of 10.20 ± 0.08 µg/mL, 9.89 ± 0.15 µg/mL and 8.97 ± 0.13 µg/mL, respectively in comparison with standard reference (ascorbic acid, IC50 = 4.57 µg/mL). Whereas, in FRAP antioxidant assay seven compounds (11c, 11e, 11i, 11k, 11l, 14d and 14h) displayed higher antioxidant activity in comparison to the reference standard BHT (C0.5FRAP = 546.2 µM). Moreover, the cytotoxic studies of the compounds 11a, 14c, 14e and 14h were found to be non-toxic in nature in 3T3 fibroblast cell lines using MTT assay.


Assuntos
Antineoplásicos/síntese química , Antioxidantes/síntese química , Oxazinas/síntese química , Quinoxalinas/síntese química , Células 3T3 , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Camundongos , Micro-Ondas , Oxazinas/farmacologia , Quinoxalinas/farmacologia , Relação Estrutura-Atividade
7.
Vasc Endovascular Surg ; : 15385744241276607, 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155150

RESUMO

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare and aggressive mesenchymal tumor, with less than 400 reported cases to date. Complete resection of the tumor with clear margins is the only proven curative treatment, providing survival benefits. Nonetheless, leiomyosarcomas in the middle segment or those extending up to it within the inferior vena cava (IVC) frequently necessitate renal reimplantation or nephrectomy, with rates varying between 56% and 75%. In this case report, we present a 65-year-old female with lower segment IVC leiomyosarcoma with middle segment extension, successfully resected and reconstructed while avoiding associated renal reimplantation or nephrectomy morbidity.

8.
Clin Case Rep ; 12(1): e8382, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38161645

RESUMO

Key Clinical Message: Primary hepatic neuroendocrine tumor, an exceptionally rare subtype, poses a diagnostic challenge. Oncological resections should be considered, even in elderly patients after following protocolized pre-operative optimizations. Abstract: Neuroendocrine tumors (NETs) are rare tumors that primarily develop in the gastrointestinal and respiratory tracts. While the liver is commonly affected by NET metastases, primary hepatic neuroendocrine tumors (PHNETs) are an exceptionally rare subtype. The characteristic slow growth and nonfunctional nature of PHNETs pose challenges in their diagnosis. Furthermore, PHNETs often exhibit a lack of unique radiological characteristics that differentiate them from other liver tumors, leading to frequent misdiagnosis as hepatocellular carcinoma. We performed left hepatectomy for PHNET in an elderly lady with prolonged stormy postoperative course. This case report of a PHNET highlights the importance of histopathology and immunohistochemistry in the diagnosis and emphasizes that oncological resection, if feasible, is the preferred treatment even in the elderly population.

9.
Cureus ; 16(7): e64205, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39130894

RESUMO

Introduction With the use of advanced instruments and techniques, the reported incidence of bile duct injury is low; however, the actual frequency might be slightly higher than reported. Most surgeons might encounter bile duct injury or bile duct-related complications in their early training days. Nevertheless, with newer techniques and technologies, cases of bile duct injuries have been mostly observed in open cholecystectomy. The predominant cause of injury is the misinterpretation of the anatomy of the bile duct, cystic duct, or aberrant right sectoral hepatic duct. Laparoscopic cholecystectomy is currently the gold standard of therapy for cholecystitis. Materials and methods The study was conducted in the Department of General Surgery at the Indira Gandhi Institute of Medical Sciences in Patna, after obtaining clearance from the ethics committee. The duration of the study was one year. Results A total of 50 patients were enrolled in the study, whose ages ranged from 20 to 55 years. They were predominantly female. The mean operative time was 68.5 ± 8.7 minutes. There were no cases of conversion to an open procedure, bile duct injury, or biliary stricture. Conclusion The injection of methylene blue into the gallbladder fundus during laparoscopic cholecystectomy is a practical, affordable, and simple procedure that does not require any special equipment or radiation exposure for the improved delineation of the gallbladder and biliary system. The use of intraoperative methylene blue could be a low-cost and simple alternative for safe laparoscopic cholecystectomy.

10.
Cureus ; 16(3): e55417, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567232

RESUMO

AIM AND OBJECTIVES: To assess the effect of gallstone disease on liver parenchyma and the prevalence and extent of liver pathology in cholelithiasis in our population at the Department of General Surgery, Indira Gandhi Institute of Medical Science (IGIMS), Patna. MATERIAL AND METHODS: The present prospective observational study was conducted on 100 either-sex patients scheduled for open or laparoscopic cholecystectomy. In all the patients, laboratory and radiological investigations were performed. An undamaged portion of the liver edge around the gallbladder fossa was selected and held by atraumatic forceps. Using sharp scissors, around 1 cm of the liver edge was taken out and sent for histopathological examination. RESULTS: The mean age of the patients was 39.28 ± 13.73 years. The majority of patients were females (69%). Pain was the predominant clinical feature in 51% of the patients, followed by vomiting (21%), nausea (18%), and indigestion (10%). In 36% of cases, the liver histology was abnormal, including steatosis, fibrosis, cholestasis, portal tract infiltration, and lobular parenchymal infiltration. A significant association was found between the duration of symptoms and abnormal histology findings (P<0.0001). CONCLUSION: Gallstone disease is associated with notable alterations in liver histology, and these changes tend to be more prevalent in individuals with a prolonged duration of symptoms.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38305340

RESUMO

Pharmaceutical development of cancer therapeutics is a dynamic area of research. Even after decades of intensive work, cancer continues to be a dreadful disease with an ever-increasing global incidence. The progress of nanotechnology in cancer research has overcome inherent limitations in conventional cancer chemotherapy and fulfilled the need for target-specific drug carriers. Nanotechnology uses the altered patho-physiological microenvironment of malignant cells and offers various advantages like improved solubility, reduced toxicity, prolonged drug circulation with controlled release, circumventing multidrug resistance, and enhanced biodistribution. Early cancer detection has a crucial role in selecting the best drug regime, thus, diagnosis and therapeutics go hand in hand. Furthermore, nanobots are an amazing possibility and promising innovation with numerous significant applications, particularly in fighting cancer and cleaning out blood vessels. Nanobots are tiny robots, ranging in size from 1 to 100 nm. Moreover, the nanobots would work similarly to white blood cells, watching the bloodstream and searching for indications of distress. This review articulates the evolution of various organic and inorganic nanoparticles and nanobots used as therapeutics, along with their pros and cons. It also highlights the shift in diagnostics from conventional methods to more advanced techniques. This rapidly growing domain is providing more space for engineering desired nanoparticles that can show miraculous results in therapeutic and diagnostic trials.


Assuntos
Nanopartículas , Neoplasias , Humanos , Distribuição Tecidual , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/uso terapêutico , Microambiente Tumoral
12.
Org Biomol Chem ; 11(48): 8410-8, 2013 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-24189837

RESUMO

A simple, mild, green, catalytic and general procedure for the direct synthesis of highly functionalized 1-methoxycarbonyl-2-aryl/alkyl-3-nitro-9H-carbazoles has been achieved in water medium via a one-pot domino Michael-Henry/aromatization reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetates with aryl/alky-substituted ß-nitroolefins under air using DABCO (30 mol%) as an organocatalyst. In addition, the bench scale synthesis can be performed without using toxic organic solvents and a biologically important new fused carbazole has been prepared.


Assuntos
Carbazóis/síntese química , Água/química , Carbazóis/química , Catálise , Química Verde , Piperazinas/química
13.
Org Biomol Chem ; 11(41): 7084-7, 2013 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-24057205

RESUMO

A simple, mild and robust method for the stereoselective synthesis of (E)-methyl α-(3-formyl-1H-indol-2-yl)-ß-aryl/alkyl-substituted acrylates via a condensation reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetate with several alkyl or aryl aldehydes using L-proline (25 mol%) as a catalyst is presented for the first time. In addition, completely metal free based high yielding methods for the syntheses of highly substituted biologically important carbazoles, γ-carbolines and the marine alkaloid prenostodione have been developed through our methodology.


Assuntos
Acrilatos/síntese química , Carbazóis/síntese química , Carbolinas/síntese química , Indóis/síntese química , Prolina/química , Acrilatos/química , Carbazóis/química , Carbolinas/química , Catálise , Indóis/química , Estrutura Molecular , Estereoisomerismo
14.
J Cancer Res Ther ; 19(3): 675-683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37470593

RESUMO

Objective: This single institutional study compared neoadjuvant concurrent chemo-radiotherapy (NACCRT) and neoadjuvant chemotherapy (NACT) followed by surgery in locally advanced middle and lower-1/3 carcinoma esophagus patients in terms of toxicity, clinical response, operative complications, disease downstaging, resection rates, pathological response, recurrence, and survival. Methods: This randomized prospective comparative study comprised 40 consecutive patients divided equally between two study arms NACCRT (n = 20; 41.4 Gy radiation dose; carboplatin area under the curve (AUC) 2/paclitaxel 50 mg/m2; 5 cycles) and NACT (n = 20; carboplatin AUC 5/paclitaxel 175 mg/m2; 2 cycles) from March 2014 to December 2016. Follow-up was done for 4 years. Chi-square test, Fischer's-exact test were used for comparative analysis and Kaplan-Meier analysis for survival. Results: Statistically significant esophagitis in NACCRT and peripheral-neuropathy in NACT was observed (P < 0.001). NACCRT recorded more postoperative complications, higher complete resection (R0) rates, and pathologically complete response (pCR). Tumor downstaging was significant in both study groups (n < 0.001). Four-year median disease-free survival (DFS) and overall survival (OS) were 28.50 months and 38 months in NACCRT versus 28 months and 35.5 months in NACT, respectively. In both NACCRT and NACT, pCR cases showed improved median DFS and OS compared to pathological partial response (pPR) (n < 0.001). Conclusion: This study demonstrated significant activity and tolerable toxicity of taxane-based therapy in NACCRT and NACT. Both groups recorded no survival benefit over each other, although pCR cases resulted in statistically significant survival advantage compared to clinical partial response. NACCRT resulted in lesser toxicity, numerically higher R0-resection, pCRs, median DFS, and OS compared to NACT.


Assuntos
Carcinoma , Neoplasias Esofágicas , Humanos , Terapia Neoadjuvante/métodos , Carboplatina , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/etiologia , Neoplasias Esofágicas/terapia , Paclitaxel , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias
15.
Indian J Otolaryngol Head Neck Surg ; 75(3): 1799-1805, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37636652

RESUMO

Conventional staging paradigm with clinical examination or imaging invariably leads to underestimation of occult metastatic neck disease in oral cavity carcinoma. The advantage of 18F-FDG PET/CT is in its ability to identify lymph nodes without morphological changes yet harboring occult metastases. We present findings of our study to evaluate diagnostic accuracy of 18F-FDG PET/CT, in detecting occult cervical lymph node metastasis in carcinoma oral cavity. In a single institution prospective study, 51 consecutive patients with histologically proven (cT1/T2) oral cavity carcinoma and clinically node negative neck (cNo), underwent 18F-FDG PET/CT before elective neck dissection of 58 neck sides. 18F-FDG PET/CT findings were compared with histopathology of dissected nodes, to calculate diagnostic accuracy. 18F-FDG PET/CT correctly characterized the occult lymph node metastasis status (true positive + true negative) in 51 of 58 neck sides, yielding diagnostic accuracy of 87.93%. Sensitivity of 18F-FDG PET/CT was 90% and specificity was 87.5%. While a positive 18F-FDG PET/CT accurately predicted the disease in only 60% (positive predictive value), a negative 18F-FDG PET/CT reasonably ruled out occult metastases in 97.67% (negative predictive value). If a decision regarding the need for neck dissection had been based solely on 18F-FDG PET/CT, the number of neck dissections would have been reduced by 74.13%. Based on diagnostic accuracy and high negative predictive value, incorporating 18F-FDG PET/CT in preoperative staging paradigm of cT1/T2 carcinoma oral cavity will guide in selection of patients in which cN0 neck can be safely observed.

16.
Cureus ; 15(5): e39420, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37362494

RESUMO

BACKGROUND AND AIM: To find the superiority of extended total extraperitoneal (E-TEP) repair and trans-abdominal pre-peritoneal (TAPP) mesh repair in inguinal hernia repair. MATERIAL AND METHODS: A total of 30 patients with a unilateral or bilateral inguinal hernia (IH), and recurrent IH, following open repair were studied. Out of 30 patients, laparoscopic TAPP or E-TEP mesh repair was performed in an equal number of inguinal hernia patients. The patient's demographic parameters, duration of surgery, postoperative hospital stay, and complications were compared. RESULTS:  In the E-TEP group, 33.33% of patients had left inguinal hernia (LIH), 60% of patients were diagnosed with right inguinal hernia (RIH) and 6.67% of patients had right inguinal and right direct hernia (RDH). In the TAPP group, 33.33% of patients had LIH and 53.33% of patients were suffering from RIH. Moreover, 6.67% of patients were diagnosed with a left inguinal direct hernia, and a similar proportion of patients had a right inguinal direct hernia. The mean duration of surgery was found to be significantly higher in the TAPP group (P<0.0000). The mean postoperative hospital stay was 2.07±0.59 and 2.80±1.32 days in E-TEP and TAPP groups, respectively (P=0.044). CONCLUSION: In the present study, E-TEP mesh repair is a superior technique in the management of inguinal hernia as compared with TAPP repair.

17.
Mol Neurobiol ; 60(3): 1690-1720, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36562884

RESUMO

A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3ß) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease. Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Tauopatias , Humanos , Proteínas tau/metabolismo , Doenças Neurodegenerativas/terapia , Tauopatias/tratamento farmacológico , Tauopatias/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fosforilação , Nanotecnologia
18.
Eur J Med Res ; 28(1): 307, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649125

RESUMO

BACKGROUND: Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood-brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. AIM: The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain-Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed. MAIN BODY: There have been reports that the SARS-CoV-2 virus can cross the blood-brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain. CONCLUSIONS: SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicações , Sistema Nervoso Central , Encéfalo , Barreira Hematoencefálica
19.
Cureus ; 14(9): e29767, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36324345

RESUMO

BACKGROUND: Out of all anorectal diseases, haemorrhoids are the most common benign disease. Haemorrhoids can be treated by various treatment modalities like medical, surgical, and instrumental. Instrumental treatment comprises rubber band ligation, sclerotherapy, and infrared and laser therapy. Out of these modalities, the rubber band ligation technique is the least invasive with a reduced rate of complications and without the need for hospitalization. Hence, the current study was conducted to evaluate the outcomes with respect to the effectiveness of rubber band ligation in grade II and III internal haemorrhoids along with the magnitude and pattern of post-procedural complications. METHODS: This is a prospective observational study, conducted on a sample of 100 patients who presented to our outdoor patient's department and were diagnosed with haemorrhoids, either grade II or III. All enrolled study patients having haemorrhoids were banded with rubber band by Barron Ligator (Precise, Canada) with local anaesthetic agent xylocaine jelly in a single session. All patients were followed on the 10th day, 1st month, and 6th month after the procedure to assess symptomatic improvement. The endpoint of this study is to know the effectiveness of rubber band ligation in different clinical parameters such as post-ligation pain or discomfort, the requirement of analgesic, any complication, and time off work. RESULTS: Out of 100 patients 17 patients had grade II and 83 patients had grade III haemorrhoids. Among them, 89% were symptomatically relieved after rubber band ligation whereas the rest 11% of patients had residual symptoms. CONCLUSION: Thus, we conclude that rubber band ligation for grade II and III haemorrhoids is simple, safer, easy-to-perform daycare procedure with lesser requirements of analgesics and without any need for anaesthesia.

20.
Maedica (Bucur) ; 17(2): 329-335, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36032608

RESUMO

Introduction:The field of abdominal wall hernias has undergone many innovations. Ventral hernias have conventionally been treated by open on-lay mesh hernioplasty, open retromuscular mesh hernioplasty (Rives-Stoppa procedure) and laparoscopic intraperitoneal mesh hernioplasty. Objective: To develop an alternative strategy where a mesh is placed in retromuscular space by minimal access technique of the laparoscopic extended view totally extraperitoneal approach (e-TEP). Methodology: This was an interventional and prospective study on series of 25 cases of either sex with age ≥18 years and ≤65 years presenting with umbilical hernia with abdominal wall defect. Laparoscopic e-TEP (extended view totally extraperitoneal repair) for umbilical hernia was performed and patients were usually discharged within 48.72 hours of the procedure. Follow-up surveillance for complications and recurrence of hernia was performed in an outpatient clinic the sixth week after surgery and by telephonic conversation every sixth months. Demographic profile, medical history, preoperative (comorbidities), perioperative and postoperative (during hospital stay) clinical profile of each patient was documented. Results:Among our study participants there was a female preponderance, with a male to female ratio of 0.47:1. Patients' ages ranged from 27 to 61 years, with a mean (SD) of 41.7 (11.4) years. Average defect size was 4.2 cm². One hernia involved divarication of recti muscles. A polypropylene mesh of size 15 x 15 cm was placed. The mean operative times were 94 minutes, ranging from 60 to 120 minutes. The average hospital stay was three days. The mean follow-up period was 12.6 months. Two patients developed seroma at umbilicus with discharge from suture site which resolved in two weeks with regular dressing. Prolonged ileus was noted in two patients, which resolved spontaneously by the fourth day. None of the patients developed surgical site infection, skin necrosis, wound dehiscence, bowel obstruction, urinary complications, or deep vein thrombosis. Also, none of the patients required conversion to open surgery. Conclusion:The current study generates evidence in support of this technique to be adapted in centers with advanced laparoscopic skills.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA