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1.
Aging Male ; 24(1): 92-94, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34319201

RESUMO

Digital rectal examination (DRE) is routinely performed as part of a urology clinical assessment in patients with a clinical suspicion of prostate cancer. An abnormal DRE or a raised prostate specific antigen (PSA) level are part of the criteria for primary care referral to secondary care due to a suspicion of prostate cancer. The current Coronavirus-19 (COVID-19) pandemic has resulted in the rapid adoption of virtual consultations in the form of telephone or video consultations making clinical examination difficult. In the case of prostate cancer diagnostic pathways, often clinicians now rely on PSA measurements and MRI, where radiological services are available, without the requirement for a DRE. We discuss the limited role DRE has in the modern prostate cancer diagnostic pathway due to the widespread adoption of MRI particularly in the COVID-19 era.


Assuntos
Exame Retal Digital , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , COVID-19 , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , SARS-CoV-2
2.
Artigo em Inglês | MEDLINE | ID: mdl-33539708

RESUMO

Si-based anode materials are considered as potential materials for high-energy lithium-ion batteries (LIBs) with the advantages of high specific capacities and low operating voltages. However, significant initial capacity loss and large volume variations during cycles are the primary restrictions for the practical application of Si-based anodes. Herein, we propose an affordable and scalable synthesis of double-layered SiOx/Mg2SiO4/SiOx composites through the magnesiothermic reduction of micro-sized SiO with Mg metal powder at 750 °C for 2 h. The distinctive morphology and microstructure of the double-layered SiOx/Mg2SiO4/SiOx composite are beneficial as they remarkably improve the reversibility in the first cycle and completely suppress the volume variations during cycling. In our material design, the outermost layer with a highly porous SiOx structure provides abundant active sites by securing a pathway for efficient access to electrons and electrolytes. The inner layer of Mg2SiO4 can constrain the large volume expansion to increase the initial Coulombic efficiency (ICE). Owing to these promising structural features, the composite prepared with a 2:1 molar ratio of SiO to Mg exhibited initial charge and discharge capacities of 1826 and 1381 mA h g-1, respectively, with an ICE of 75.6%. Moreover, it showed a stable cycle performance, maintaining high capacity retention of up to >86.0% even after 300 cycles. The proposed approach provides practical insight into the mass production of advanced anode materials for high-energy LIBs.

3.
Cancer Lett ; 498: 1-18, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931887

RESUMO

Androgen deprivation therapy (ADT) and androgen receptor (AR) signaling inhibitors are front-line treatments for highly aggressive prostate cancer. However, prolonged inhibition of AR triggers a compensatory activation of PI3K pathway, most often due to the genomic loss of tumor suppressor PTEN, driving progression to the castration-resistant prostate cancer (CRPC) stage, which has very poor prognosis. We uncovered a novel mechanism of PTEN downregulation triggered by LIMK2, which contributes significantly to CRPC pathogenesis. LIMK2 is a CRPC-specific target. Its depletion fully reverses tumorigenesis in vivo. LIMK2 phosphorylates PTEN at five sites, degrading and inhibiting its activity, thereby driving highly aggressive oncogenic phenotypes in cells and in vivo. PTEN also degrades LIMK2 in a feedback loop, which was confirmed in prostates from PTEN-/- and PTEN+/+ mice. LIMK2 is also the missing link between hypoxia and PTEN degradation in CRPC. This is the first study to show a feedback loop between PTEN and its regulator. Uncovering the LIMK2-PTEN loop provides a powerful therapeutic opportunity to retain the activity and stability of PTEN protein by inhibiting LIMK2, thereby halting the progression to CRPC, ADT-resistance and drug-resistance.


Assuntos
Quinases Lim/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Animais , Carcinogênese/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo/fisiologia , Células HEK293 , Humanos , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Nus , Células PC-3 , Fosfatidilinositol 3-Quinases/metabolismo , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais/fisiologia
4.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158056

RESUMO

SPOP, an adaptor protein for E3 ubiquitin ligase can function as a tumor-suppressor or a tumor-enhancer. In castration-resistant prostate cancer (CRPC), it inhibits tumorigenesis by degrading many oncogenic targets, including androgen receptor (AR). Expectedly, SPOP is the most commonly mutated gene in CRPC (15%), which closely correlates with poor prognosis. Importantly, 85% of tumors that retain wild-type SPOP show reduced protein levels, indicating that SPOP downregulation is an essential step in CRPC progression. However, the underlying molecular mechanism remains unknown. This study uncovered the first mechanism of SPOP regulation in any type of cancer. We identified SPOP as a direct substrate of Aurora A (AURKA) using an innovative technique. AURKA directly phosphorylates SPOP at three sites, causing its ubiquitylation. SPOP degradation drives highly aggressive oncogenic phenotypes in cells and in vivo including stabilizing AR, ARv7 and c-Myc. Further, SPOP degrades AURKA via a feedback loop. SPOP upregulation is one of the mechanisms by which enzalutamide exerts its efficacy. Consequently, phospho-resistant SPOP fully abrogates tumorigenesis and EMT in vivo, and renders CRPC cells sensitive to enzalutamide. While genomic mutations of SPOP can be treated with gene therapy, identification of AURKA as an upstream regulator of SPOP provides a powerful opportunity for retaining WT-SPOP in a vast majority of CRPC patients using AURKA inhibitors ± enzalutamide, thereby treating the disease and inhibiting its progression.

5.
Bioorg Med Chem Lett ; 30(22): 127544, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32920143

RESUMO

New indole-tethered [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (8a-j) and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) were synthesized using [4+2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with indole-ketenes. All molecular hybrids were structurally characterized by spectroscopic techniques (IR, NMR, and HRMS) and screened for their anti-pancreatic cancer activity in vitro. The [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) showed stronger anti-pancreatic cancer activity than the [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrids (8a-j) against the PANC-1 cell line. Compound 9d bearing an ortho-chlorophenyl moiety emerged as the most potent anti-pancreatic cancer agent with an IC50 value of 7.7 ± 0.4 µM, much superior to the standard drug Gemcitabine (IC50 > 500 µM). The discovery of these [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids elicits their potentials as pursuable candidates for pancreatic cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Oxidiazóis/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Pirimidinas/farmacologia , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/química , Estrutura Molecular , Oxidiazóis/química , Neoplasias Pancreáticas/patologia , Pirimidinas/química , Relação Estrutura-Atividade , Tiadiazóis/química
6.
Nat Rev Urol ; 17(11): 643-649, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32968240

RESUMO

Despite advances in robotic-assisted surgery (RAS) in the past two decades, control of the robotic system currently remains under the command of a human surgeon. Historically, urology has pioneered new surgical techniques and technologies. Now, autonomous RAS is on the horizon and the first data from clinical trials of autonomous RAS in urology are being published. Automation takes control away from the surgeon but promises standardization of techniques, increased efficiency, potentially reduced complication rates and new ways of integrating intra-operative imaging. Preclinical and clinical evidence is emerging that supports the use of autonomous robotic-assisted urological surgery. Use of autonomous technologies in the operating theatre will directly affect the role of the urological surgeon. Integration of autonomous RAS can be viewed as a positive aid, but it might also be perceived as a threat to the future urological surgeon.

7.
Urology ; 146: e17-e19, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32805292

RESUMO

We report a 70-year-old gentleman who attended the emergency department with a 1 day history of sudden onset right-sided flank pain. He was on warfarin due to metallic mitral valve. On presentation, he was hemodynamically stable, but his international normalized ratio was deranged at 4.7. An initial noncontrast computed tomography (CT) scan of abdomen showed a large right retroperitoneal hematoma and subsequent CT renal angiogram revealed evidence of active bleeding. There were dilemmas whether or not to reverse the effect of warfarin, proceed with angioembolization or explore the patient surgically. Here, we have addressed these issues.

8.
Cureus ; 12(5): e8371, 2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32626615

RESUMO

Introduction Organophosphate ingestion is the commonest cause of self-harm encountered at poison control centers in Pakistan. It usually affects a young populous. Organophosphates are found in various forms and formulations that are easily accessible to the general public. These compounds are extremely potent poisons causing rapid clinical deterioration with minimal ingestion or exposure. Signs and symptoms can range from mild or none to severe such as bradycardia, miosis, fasciculations, seizures and altered level of consciousness. Poisoning severity is measured using the Peradeniya Organophosphorus Poisoning (POP) scale. Mortality rates are relatively low for mild to moderate disease. Severe disease as calculated by the POP carries an exceptionally high mortality rate. The National Poisoning Control Centre (NPCC) at Jinnah Postgraduate Medical Centre, Karachi treats an extraordinary number of poisoning cases on a daily basis. Despite this data pertaining specifically to OP ingestion is nearly absent. There have been no studies analyzing the various aspects of organophosphate poisoning in the last 30 years to the best of our knowledge. Here, we look to rectify this. Aims To evaluate the demographics, severity scores and outcomes of organophosphate poisoning cases in the last year from the NPCC, Karachi. Methods This was a retrospective study. It was held from 1st January 2019 to 31st December 2019. All data was recorded from patients admitted to the NPCC with a proven diagnosis of organophosphate poisoning. Results Three thousand and three hundred patients were inducted into this study. Over 3/4th of the patients were teenagers or aged less than 30 years. Almost all referrals were made from within the city. Overall survival rate at 28 days was 89.45%. Most patients presented with mild to moderate disease as calculated by the POP; severe disease had a mortality rate of nearly 50%. Conclusion Organophosphates make up a significant portion of all cases of poisoning treated at the NPCC. The POP is an excellent tool to evaluate disease severity. Overall survival rates are good but mortality rate is high for severe disease even in young patients.

9.
Br J Hosp Med (Lond) ; 81(7): 1-3, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32730162

RESUMO

The COVID-19 pandemic has caused major disruptions to the healthcare system, including increased reliance on virtual services, particularly clinic appointments. This leads to difficulty in obtaining informed consent; the vast majority of patients now need to be consented on the day of the procedure. To reduce problems with this process, the practice of obtaining electronic consent may be the correct way forward.


Assuntos
Infecções por Coronavirus/epidemiologia , Consentimento Livre e Esclarecido , Pneumonia Viral/epidemiologia , Telemedicina , Betacoronavirus , COVID-19 , Humanos , Aplicativos Móveis , Pandemias , SARS-CoV-2
11.
Cancers (Basel) ; 12(3)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178290

RESUMO

Multifunctional protein YBX1 upregulation promotes castration-resistant prostate cancer (CRPC). However, YBX1 protein abundance, but not its DNA status or mRNA levels, predicts CRPC recurrence, although the mechanism remains unknown. Similarly, the mechanism by which YBX1 regulates androgen receptor (AR) signaling remains unclear. We uncovered the first molecular mechanism of YBX1 upregulation at a post-translational level. YBX1 was identified as an Aurora Kinase-A (AURKA) substrate using a chemical screen. AURKA phosphorylates YBX1 at two key residues, which stabilizes it and promotes its nuclear translocation. YBX1 reciprocates and stabilizes AURKA, thereby initiating a synergistic loop. Notably, phospho-resistant YBX1 is dominant-negative and fully inhibits epithelial to mesenchymal transition, chemoresistance, drug-resistance and tumorigenesis in vivo. Unexpectedly, we further observed that YBX1 upregulates AR post-translationally by preventing its ubiquitylation, but not by increasing its transcription as reported before. Uncovering YBX1-mediated AR stabilization is highly significant due to AR's critical role in both androgen-sensitive prostate cancer and CRPC. As YBX1 inhibitors are unknown, AURKA inhibitors provide a potent tool to degrade both YBX1 and AR simultaneously. Finally, this is the first study to show a reciprocal loop between YBX1 and its kinase, indicating that their concomitant inhibition will be act synergistically for CRPC therapy.

13.
Cureus ; 11(7): e5167, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31528517

RESUMO

Introduction The most important function of vitamin D is to maintain normal calcium homeostasis. Various factors play an important role but the most significant aspect of its normal physiological functioning is exposure to sunlight, therefore, it is also known as the sunshine vitamin. In adults, a prolonged deficiency of vitamin D (calcitriol) can lead to osteomalacia while a lower deficiency (insufficiency) is associated with various non-specific symptoms. Vitamin D deficiency has been observed in developed and developing countries, including the Middle East and the subcontinent. Vitamin D is mandatory for the maintenance of health due to the presence of its highly specific receptors, Vitamin D receptors, in all body tissues and its regulatory role in the encoding of more than 200 genes. The deficiency of Vitamin D, therefore, could affect any tissue or body system. Most interventions for this are done through outpatient departments (OPDs). The burden of vitamin D deficiency is affected by seasonal variation in our part of the world as well as internationally; data show a marked variation, however. Generalized body ache is a vague symptom. It is one of the most common complaints seen at the OPD and can be a manifestation of many a disease. But a correlation with low vitamin D levels has been observed previously. Whether this relation is affected by seasonal variation remains unascertained and data on the above-mentioned relationship for Pakistan are scarce. Objective We aim to evaluate the incidence of vitamin D deficiency in different seasons in the adult Karachi population presenting in medical OPDs with a generalized body ache. Materials and methods This study was conducted at Medical Ward 5, Jinnah Postgraduate Medical Center, Karachi, from January 2016 to December 2016. Data were collected from the OPD that was held twice-weekly (Mondays and Fridays). Only patients who exclusively complained of "generalized body ache" were inducted into the study. Patients with minor complaints, such as headache, backache, fatigue, and lethargy, were also seen only if there were no comorbidity at all. Meticulous lab and clinical workup were done to rule out potentially not-so-benign causes of the symptoms. Patients 18 years or older were inducted into the study. Once written consent was taken, Vitamin D levels were carried out via the COBAS (Roche Diagnostics, Mannheim, Germany) method. A vitamin D level of ≤30 ng/ml was considered deficient. Results were obtained within a week, and data were recorded and analyzed. Summer was defined as three months either side of the summer solstice (June 21) and winter was defined as three months either side of the winter solstice (December 21). Results A total of 577 patients were inducted into the study. The mean age of the patients was 39.33 ± 10.23 years. The patients were predominantly female (72.7%) and housewives. Of these, 298 (51.64%) had a vitamin D deficiency; in summer, the incidence was 44.23% and in winter, it was 60.37%. The mean level of vitamin D in deficient patients was 25.06±8.74 ng/dl. Conclusion Vitamin D levels are significantly decreased in patients complaining of generalized body ache even without any comorbidity. These affect predominantly the middle-aged female population. Seasonal variation occurs with most patients presenting during the winter months, along with lower means.

14.
Cell Biol Int ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393067

RESUMO

We previously found that km23-1/DYNLRB1 is required for transforming growth factor-ß (TGFß) production through Ras/ERK pathways in TGFß-sensitive epithelial cells and in human colorectal cancer (CRC) cells. Here we demonstrate that km23-1/DYNLRB1 is required for mitogen-activated protein kinase kinase (MEK) activation in human CRC cells, detected by km23-1/DYNLRB1-siRNA inhibition of phospho-(p)-MEK immunostaining in RKO cells. Furthermore, we show that CRISPR-Cas9 knock-out (KO) of km23-1/DYNLRB1 reduced cell migration in two additional CRC models, HCT116 and DLD-1. Of interest, in contrast to our previous work showing that dynein motor activity was required for TGFß-mediated nuclear translocation of Smad2, in the current report, we demonstrate for the first time that disruption of dynein motor activity did not reduce TGFß-mediated activation of MEK1/2 or c-Jun N-terminal kinase (JNK). Moreover, size exclusion chromatography of RKO cell lysates revealed that B-Raf, extracellular signal-regulated kinase (ERK), and p-ERK were not present in the large molecular weight fractions containing dynein holocomplex components. Furthermore, sucrose gradient fractionation of cell lysates from both HCT116 and CBS CRC cells demonstrated that km23-1/DYNLRB1 co-sedimented with Ras, p-ERK, and ERK in fractions that did not contain components of holo-dynein. Thus, km23-1/DYNLRB1 may be associated with activated Ras/ERK signaling complexes in cell compartments that do not contain the dynein holoprotein complex, suggesting dynein-independent km23-1/DYNLRB1 functions in Ras/ERK signaling. Finally, of the Ras isoforms, R-Ras is most often associated with cell migration, adhesion, and protrusive activity. Here, we show that a significant fraction of km23-1/DYNLRB1 and RRas wase co-localized at the protruding edges of migrating HCT116 cells, suggesting an important role for the km23-1/DYNLRB1-R-Ras complex in CRC invasion.

15.
Biochem Insights ; 12: 1178626418818182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733628

RESUMO

Background: Escherichia coli cytosine deaminase (CD) converts 5-fluorocytosine (5-FC), a prodrug, into 5-fluorouracil (5-FU), a chemotherapeutic drug. However, the poor binding affinity of CD towards 5-FC as compared to the natural substrate cytosine, limits its application towards a successful suicide gene therapy. Although F186W mutant was developed to enhance the effect of wild-type CD, still scope for its improvement remains to further minimize the dose-dependent cytotoxicity of the drugs. Hence, in this study, we employ the anti-tumour attribute of the gap junction forming protein connexin-43 (Cx43) in conjunction with CD or F186W mutant. Methods: Lipofectamine was used to co-transfect CD/F186W-pVITRO2 and Cx43-pEGFP-N1 plasmids construct into MCF-7 cells. Comparative analysis of cell viability was observed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) and trypan blue-based assays. To further confirm the mode of cell death was apoptosis, propidium iodide and annexin V/7-aminoactinomycin D (7-AAD)-based apoptosis assays were performed. Results: Semi-quantitative polymerase chain reaction (PCR) confirmed the expression of both Cx43 and CD/F186W genes after transfection. Furthermore, cell viability assays revealed the enhanced activity of F186W-Cx43 compared with CD-Cx43 and F186W alone. The trend of the reduction in cell viability was also reflected in the flow cytometry-based apoptosis analyses. Overall, F186W-Cx43 combination demonstrated its superiority over the CD-Cx43 and F186W mutant alone. Conclusions: The enhanced cytotoxic activity of F186W mutant was further amplified by gap junction protein Cx43.

16.
J Endourol Case Rep ; 5(3): 113-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32775641

RESUMO

Background: Filariasis is a tropical disease caused by infection with nematode parasites of the Filarioidea family. Filariasis is an endemic disease in parts of India, Sub-Saharan Africa, and Southeast Asia. Filariasis is a progressive disease predominantly affecting the lymphoreticular system, which can result in genitourinary complications (hydrocele, scrotal pain, and infertility), lymphedema, and elephantitis. Retroperitoneal fibrosis has a broad etiology, including secondary to chronic infection. Currently an estimated 25 million men are suffering from lymphatic filariasis with urogenital involvement worldwide. Case Presentation: We present a rare case of a 40-year-old man presenting with fever, groin lymphadenopathy, and a history of infertility. Imaging confirmed significant hydronephrosis and retroperitoneal fibrosis. Filariasis serology was positive. Prior bilateral testicular biopsy demonstrated chronic inflammation and atrophy. Disease course was not improved by empirical eradication and supportive retrograde ureteral stenting. The patient developed elephantitis and progressive retroperitoneal fibrosis leading to a solitary functioning right kidney with nephrostomy. Conclusion: Urologists should be aware of index presentations of filariasis and its associated urological complications, particularly in the travelling adult population in whom the etiology of renal impairment and infertility remains unclear.

17.
Sci Rep ; 8(1): 17357, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478455

RESUMO

To understand the burgeoning challenges of metastasis, a microchannel of 35 µm diameter, constricted to 7 µm for a distance of 200 µm in a total length of 3 mm, was designed and fabricated using a mask aligner made of polydimethylsiloxane (PDMS) to mimic in vivo capillaries. A thin glass cover-slide was mounted on top to monitor the motion of single or aggregated malignant HeLa cells (size 17-30 µm) microscopically through the constricted microchannel at a constant flow rate of 30 µl/h. Quantitative deconvolution of high-speed videographs of a single cell of 30 µm revealed cellular deformation while passing through constriction, having elongation index, average transit velocity and entry time of 2.67, 18 mm/s and 5.1 ms, respectively. Morphological analysis of live and apoptotic cells by dual staining with Acridine Orange/Ethidium Bromide demonstrated retention of a significant viable cell population after exit through the constriction and a viability index of 50% was quantified by dye exclusion assay. The cumulative data for microfluidic parameters, morphology and relevant metastatic MMP2 gene expression efficiency measured by real-time polymerase chain reaction revealed retention of virulence potency that could possibly cause metastasis, would be beneficial in developing futuristic MEMS device for cancer theranostics.


Assuntos
Sobrevivência Celular/fisiologia , Metástase Neoplásica/patologia , Neoplasias do Colo do Útero/patologia , Laranja de Acridina/administração & dosagem , Apoptose/fisiologia , Linhagem Celular Tumoral , Etídio/administração & dosagem , Feminino , Células HeLa , Humanos , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos
18.
Nanomedicine (Lond) ; 13(3): 283-295, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29345211

RESUMO

AIM: To develop methotrexate (MTX) templated luminescent gold nanoclusters (NCs) as a single unit nanotheranostic for cancer therapy and to assess its potential as an alternative to the parent drug, for drug delivery vehicles (DDVs). METHODS: Theranostics were synthesized and extensively characterized. The stability of the theranostic and its bioimaging aptitude were evaluated. The antiproliferative propensity of the theranostic was gauged with cell viability assays and was supplemented with cytometry-based assays. Feasibility of delivering the MTX NCs instead of parent drug on a DDV was also checked. RESULTS: MTX NCs displayed remarkable physical characteristics and augmented cytotoxicity with a robust stability in phosphate-buffered saline and serum. MTX NCs also demonstrated their amenability to being loaded on a DDV (chitosan folic acid nanoparticles) while retaining their physical and cytotoxic profile. CONCLUSION: Generation of next level drug-based theranostics with the potential of replacing the free drug in drug delivery platforms.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas/administração & dosagem , Metotrexato/farmacologia , Neoplasias/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Ouro/química , Células HeLa , Humanos , Nanopartículas Metálicas/química , Metotrexato/química , Neoplasias/patologia , Nanomedicina Teranóstica
19.
J Neurol Surg A Cent Eur Neurosurg ; 79(4): 279-284, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29346831

RESUMO

BACKGROUND/AIMS: The use of single/dual external ventricular drains (EVD) for reducing intraventricular hemorrhage (IVH) is under investigation. A randomized controlled trial was conducted to compare postoperative reduction of IVH volume using single- and dual-catheter drainage in spontaneous IVH patients. We investigated factors that may influence an effective hematoma volume reduction by EVDs. MATERIALS AND METHODS: The average cerebrospinal fluid (CSF) drainage volumes were analyzed. Computed tomography (CT) scans were performed on admission, 24 hours and 48 hours after EVD placement, and then on days 5 and 8. Patient group 1 was treated with a single EVD; patient group 2 was treated with bilateral EVDs. The IVH volume was calculated in all ventricles. A multivariate analysis was conducted to investigate variables that can influence the extent of hematoma volume reduction with a bilateral EVD. Regression followed by a Pearson correlation was performed to observe the strength of association of cofounders with the IVH volume reduction. RESULTS: The percentage of IVH volume change was found to be significantly higher in the dual-catheter group compared with the single-catheter group (p = 0.0034) after 5 days of EVD. The mean reduction in IVH volume was 17.36 (mL) in patients ≤ 45 years of age and 20.50 (mL) in patients > 45 years. The multivariate analysis suggested the following significant predictors for IVH volume reduction: age of the patient (p = 0.011) and longer duration (days) of EVD (p = 0.028). The age of the patient had a weak positive association and duration of EVD had a positive association with the IVH volume reduction. CONCLUSION: Intraventricular drainage via bilateral EVDs may provide a better draining of blood-mixed CSF because it led to faster clot clearance. It is suggested that a longer duration of bilateral EVDs may lead to a greater reduction in IVH volume. Older patients may experience a greater IVH volume reduction by EVD because the volume of CSF increases with cerebral atrophy.


Assuntos
Cateteres , Hemorragia Cerebral/cirurgia , Ventrículos Cerebrais/cirurgia , Drenagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Tempo , Resultado do Tratamento
20.
ACS Appl Mater Interfaces ; 10(4): 3282-3294, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-29278317

RESUMO

Transferrin (Tf)-templated luminescent blue copper nanoclusters (Tf-Cu NCs) are synthesized. They are further formulated into spherical Tf-Cu NC-doxorubicin nanoparticles (Tf-Cu NC-Dox NPs) based on electrostatic interaction with doxorubicin (Dox). The as-synthesized Tf-Cu NC-Dox NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Förster resonance energy transfer (FRET) within the Tf-Cu NC-Dox NPs exhibited striking red luminescence, wherein the blue luminescence of Tf-Cu NCs (donor) is quenched due to absorption by Dox (acceptor). Interestingly, blue luminescence of Tf-Cu NCs is restored in the cytoplasm of cancer cells upon internalization of the NPs through overexpressed transferrin receptor (TfR) present on the cell surface. Finally, gradual release of Dox from the NPs leads to the generation of its red luminescence inside the nucleus. The biocompatible Tf-Cu NC-Dox NPs displayed superior targeting efficiency on TfR overexpressed cells (HeLa and MCF-7) as compared to the cells expressing less TfR (HEK-293 and 3T3-L1). Combination index (CI) revealed synergistic activity of Tf-Cu NCs and Dox in Tf-Cu NC-Dox NPs. In vivo assessment of the NPs on TfR positive Daltons lymphoma ascites (DLA) bearing mice revealed significant inhibition of tumor growth rendering prolonged survival of the mice.


Assuntos
Nanopartículas , Animais , Linhagem Celular , Cobre , Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Nanomedicina Teranóstica , Transferrina
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