RESUMO
This case report presents the findings of colon adenocarcinoma in a young adult male who presented with vague abdominal pain as his only complaint, suspicious of appendicitis. The patient underwent abdominal computed tomography (CT) imaging for further evaluation of his abdominal pain. CT findings showed pericecal fat stranding and prominent lymph nodes concerning for acute appendicitis, but the appendix could not be adequately visualized; due to the indeterminate CT findings, general surgery proceeded to perform an exploratory laparotomy on the patient and removed an appendiceal mass-like structure that was revealed to be invasive adenocarcinoma of the colon per pathology. This case report details the radiological and pathological findings of colorectal adenocarcinoma presenting similarly to acute appendicitis and demonstrates that colorectal adenocarcinoma must be considered on the list of differentials in young adults presenting with abdominal pain and unclear CT imaging.
RESUMO
BACKGROUND: Although various treatment options are available for spinoglenoid cyst, including conservative and surgical methods, there is no standard guideline for its surgical decompression. Thus, the purpose of the study was to correlate the size of the spinoglenoid notch ganglion cyst (GC) as revealed by magnetic resonance imaging (MRI) with electrophysiological alterations, muscle power, and pain severity, and to estimate a cut-off value of cyst size to perform a decompression. METHODS: Between January 2010 and January 2018, the patients with a GC at the spinoglenoid notch diagnosed on MRI, and who had a minimum follow-up of 2 years after the decompression were included. Maximum cyst diameter as measured on MRI was used for comparison. Electromyography (EMG) and nerve conduction velocity (NCV) studies were performed before the surgery. Peak torque deficit (PTD) percentage compared to opposite shoulder was calculated preoperatively and at 1 year after surgery. Pain severity was estimated using visual analogue scale (VAS) preoperatively. RESULTS: Ten (50%) of 20 patients with GC > 2.2 cm and 1 (5.9%) of 17 patients with GC < 2.2 cm showed EMG/NCV abnormalities (p = 0.019). There was a correlation between the cyst size and the positive EMG/NCV findings (Correlation coefficient (CC) = 0.535, p < 0.001). The preoperative peak torque deficit on the external rotation was correlated with the positive EMG/NCV findings (CC = 0.373, p = 0.021). The PTD was improved significantly at 1 year postoperatively in patients with a GC size >2.2 cm (p = 0.029). The cyst size was not related to the preoperative pain VAS and muscle power. CONCLUSIONS: The spinoglenoid cyst size >2.2 cm, but not pain severity or muscle power, correlates with the positive finding of EMG for compressive suprascapular neuropathy. The GC size >2.2 cm can be a reference to decide the need of decompression surgery. LEVEL OF EVIDENCE: IV, case series.
RESUMO
Total Knee Arthroplasty (TKA) has seen many advancements over the years. One such advancement is development of locking mechanism for polyethylene insert in modular implants. It aims to reduce micro motion and wear problems. Disengagement of locking pin from insert after primary TKA without trauma is rare complication. The author describes a rare case of disengagement of the polyethylene insert locking pin in primary total knee arthroplasty. Disengagement of the locking clip was observed 8 months after index operation without any trauma.
RESUMO
Carcinoma arising in ectopic breast tissue is a rare entity, especially in males, in whom the diagnosis is often delayed due to a low index of suspicion. Conventional imaging techniques fail to characterize the tumor, adding further to the diagnostic dilemma. We report the first case in our knowledge of an extramammary primary breast carcinoma arising in the inguinal region in a male. Our patient, a 69-year-old male, presented with a swelling in the left inguinal region, which was excised and diagnosed as luminal A type invasive ductal carcinoma. He received adjuvant external beam radiotherapy (50 Gy administered in 25 fractions) and tamoxifen. A follow-up examination performed 6 months after the completion of the last dose of radiotherapy showed no residual disease. The modalities of treatment for such tumors have been discussed, with emphasis on surgery and radiotherapy, given the aggressive nature of the disease.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Idoso , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/terapia , Humanos , Masculino , Neoplasia Residual , Tamoxifeno/uso terapêuticoRESUMO
BACKGROUND Diagnosing cerebral venous thrombosis (CVT) poses significant challenges owing to a nonspecific clinical presentation, poorly correlated laboratory biomarkers, and low sensitivity of non-contrast head computed tomography (CT). We describe a case of missed CVT diagnosis, due to low clinical suspicion and nonrecognition of anemia as a prothrombotic factor, especially during an ulcerative colitis (UC) flare. A recently proposed CVT clinical probability score can guide clinicians in pursuing further neurovascular imaging. CASE REPORT A 35-year-old man, with treatment-naive UC, presented to the Emergency Department (ED) with new-onset diffuse headache, 4 weeks of bloody diarrhea, and weight loss. Initial ED laboratory studies revealed severe anemia and unremarkable non-contrast head CT. Two days later, the patient returned to the ED for worsening headache. Non-contrast head CT revealed a left temporal hypodensity. This was later confirmed as acute ischemia on magnetic resonance imaging (MRI). MR venogram revealed thrombosis of the left transverse and sigmoid sinuses, leading to initiation of therapeutic subcutaneous anticoagulation. Repeat MRI, secondary to worsening headache, revealed the development of petechial hemorrhages within the core of venous ischemia in the left temporal lobe. Therapeutic anticoagulation, along with symptomatic management of UC, led to clinical stabilization. CONCLUSIONS CVT should be suspected in patients with UC, especially in the context of anemia, presenting with new-onset or worsening headaches. Recognizing anemia as a thrombogenic factor is crucial. Diagnosis of CVT is challenging due to non-focal symptoms and poorly correlating diagnostic tests. We endorse implementing the CVT clinical probability score into AHA/ASA CVT guidelines to enhance diagnostic accuracy.
Assuntos
Trombose Intracraniana , Trombose Venosa , Adulto , Cefaleia/etiologia , Humanos , Trombose Intracraniana/diagnóstico , Masculino , Neuroimagem , Flebografia , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Stroke is one of the top contributors to burden of disability-adjusted life-years worldwide. Family physicians have key role in optimising secondary prevention following stroke by managing clinical risk factors and promoting overall control in accordance with clinical practice guidelines. METHODS: Our objectives were: (i) to examine level of overall risk factor control together with control of singular risk factors one-year after an index-stroke event in individuals attending primary care facility and (ii) to describe factors associated with satisfactory risk factors control in individuals following stroke. STUDY DESIGN: Retrospective cohort study. We conducted a study looking retrospectively at records from our electronic chronic disease database. Our study included individuals following stroke who visited primary care setting in Singapore between January 2012 to December 2016. RESULTS: There were 24,240 individuals in our study. Overall control was better in individuals without diabetes following stroke (49.2%) as compared to those with diabetes (28.1%). Among individuals without diabetes following stroke, factors significantly associated with overall control were sex (male) [OR (reference: female): 1.23, 95% CI: 1.10, 1.39], ethnicity (Malay) [OR (reference: Chinese): 0.72, 95% CI: 0.58, 0.90], BMI (high risk) [OR (reference: low risk): 0.72, 95% CI: 0.62, 0.84) and atrial fibrillation [OR: 1.47, 95% CI: 1.21, 1.78]. Among individuals with diabetes following stroke, factors significantly associated with overall control were sex (male) [OR (reference: female): 1.28, 95% CI: 1.12, 1.46], ethnicity (Malay) [OR (reference: Chinese): 0.81, 95% CI: 0.65, 0.99], ethnicity (Indian) [OR (reference: Chinese): 0.70, 95% CI: 0.55, 0.88], BMI (high risk) [OR (reference: low risk): 0.71, 95% CI: 0.59, 0.84), BMI (moderate risk) [OR (reference: low risk): 0.84, 95% CI: 0.72, 0.98), atrial fibrillation [OR: 1.24; 95% CI: 1.02, 1.51], chronic kidney disease [OR: 0.63, 95% CI: 0.54, 0.72] and smoking status [OR: 0.68, 95% CI: 0.54, 0.88]. CONCLUSION: We reported sub-optimal level of overall control. Among individuals following stroke, those with diabetes had higher proportion of sub-optimal control as compared to those without diabetes. Irrespective of diabetic status, being female, having high BMI, and of Malay ethnicity as compared to Chinese ethnicity were associated with poorer overall risk factor control.
Assuntos
Atenção Primária à Saúde , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND Wernicke's encephalopathy (WE), a commonly misdiagnosed and underdiagnosed pathology, presents with altered mental status, ataxia, and ophthalmoplegia. WE is most commonly caused by excessive alcohol use, but also has diverse nonalcoholic etiologies. Here we describe 2 cases of nonalcoholic WE with different etiologies that were initially misdiagnosed due to lack of correlation of magnetic resonance imaging (MRI) findings with clinical information. CASE REPORT Patient A, a 50-year-old woman with recent gastric sleeve surgery, presented with horizontal gaze-evoked nystagmus, ataxia, and altered mental status. MRI fluid-attenuated inversion recovery (FLAIR) revealed isolated bilateral, symmetrical, thalamic hyperintensities, initially diagnosed as variant Creutzfeldt-Jakob disease. A review of imaging and clinical presentation provided an alternate diagnosis of nonalcoholic WE secondary to nutritional deficiency. Intravenous (IV) thiamine improved symptoms with resolution of MRI findings 6 months later. Patient B, a 64-year-old woman, presented with nausea, vomiting, dizziness, altered mental status, and weight loss. MRI FLAIR revealed isolated bilateral, symmetrical, thalamic hyperintensities, initially determined to be ischemia, prompting stroke management. A diagnosis of nonalcoholic WE was suggested, given the patient's low thiamine levels and history of malnutrition, and was confirmed by her excellent therapeutic response to IV thiamine. CONCLUSIONS Nonalcoholic WE remains a challenging diagnosis because of the variable clinical presentation, myriad of underlying etiologies, and lack of standardized diagnostic laboratory tests. A multidisciplinary approach with close collaboration between the radiologist and clinical care team is critical to narrow down the differential and initiate correct management. WE is a reversible disease with catastrophic consequences if it is not recognized and treated promptly.
Assuntos
Hóquei , Pulvinar , Encefalopatia de Wernicke , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tiamina/uso terapêutico , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico , Encefalopatia de Wernicke/etiologiaRESUMO
PURPOSE: A mobile-bearing (MB) posterior-stabilized total knee arthroplasty (TKA) system with ball and socket post-cam mechanism has been developed with the aims of better prosthesis fit and enhanced stability. However, the data are limited to compare its clinical outcomes with an already established fixed-bearing (FB) implant design. METHODS: This is a prospective randomized study comparing 260 patients in the MB group and 133 patients in FB group with a minimum 2 years of follow-up. Intraoperative variables, post-operative functional outcomes and incidence of adverse events were compared. RESULTS: MB group showed better prosthesis fit as the incidence of over-hang of femoral component at junction (medial: 1% vs. 5% and lateral: 2% vs 4%, p < 0.001) and trochlea (medial: 2% vs 30%, p = 0.042 and lateral: 13% vs 21%, p = 0.015) was less than FB group. MB group also showed better gap balancing as the incidence of medio-lateral gap difference more than 2 mm was less in flexion (2.3% vs. 16%, p < 0.001) and extension (3.1% vs. 9.8%, p = 0.005). Post-operative functional outcomes and incidence of adverse events showed no difference between the two groups at 2 years. CONCLUSIONS: New MB design offers similar functional outcomes and stability along with better intraoperative prosthesis fit and gap balancing compared to an established fixed-bearing design. Hence, this new MB design could be an alternative prosthesis of choice for posterior-stabilized TKA. LEVEL OF EVIDENCE: I.
Assuntos
Artroplastia do Joelho/instrumentação , Prótese do Joelho/estatística & dados numéricos , Idoso , Artroplastia do Joelho/reabilitação , Feminino , Seguimentos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Desenho de Prótese , Amplitude de Movimento Articular , Recuperação de Função FisiológicaRESUMO
BACKGROUND: Pelvic fractures represent one of the most challenging clinical problems in which an urgent multidisciplinary approach is required. The early management in a suspected pelvic fracture starts with the good radiological evaluation. The standard radiographic view includes the anteroposterior, inlet and outlet views. The inlet and outlet views are taken with 45° tilt from anteroposterior plane. However, recent studies have shown that there is significant individual variation within the population and these values should be redefined. MATERIAL AND METHODS: This is a retrospective study carried out in a tertiary care teaching institute. Total 110 patients (including 42 female and 68 male patients) of age older than 18 years, who had a routine pelvic Computed Tomography (CT) scan performed for any indications unrelated to pelvic pathologies were included. STATISTICAL ANALYSIS: Mean and standard deviation were calculated. For each angle measured, the effect of age was determined and a comparison was made between male and female patients, p value <0.05 is considered significant. RESULTS: The mean angle of caudal tilt for the ideal screening inlet view was 33° +/-8 (16.3-31.3) and the mean angle of cephalic tilt for the ideal screening outlet view was 56° +/-9 (51.6-81.8). CONCLUSION: This study re-evaluated the optimal inlet and outlet angles in Indians and demonstrated that the mean angles needed to create an ideal pelvic inlet and outlet views are 33° and 56° respectively.
RESUMO
OBJECTIVE: We compared the cost-effectiveness of two inpatient diabetes care models: one offered by a specialized diabetes team (SDT) versus a primary service team (PST). RESEARCH DESIGN AND METHODS: We retrospectively evaluated 756 hospital admissions of patients with diabetes to non-critical care units over 6 months. Out of 392 patients who met the eligibility criteria, 262 were matched 1:1 based on the mean of the initial four blood glucose (BG) values after admission. Primary outcomes were 30-day readmission rate and frequency, hospital length of stay (LOS) and estimated hospital cost. Secondary outcomes included glycemic control and BG variability. RESULTS: Diabetes complexity and in-hospital complications were significantly higher among patients treated by SDT versus PST. Thirty-day readmission rate to medical services was lower by 30.5% in the SDT group versus the PST group (P<0.001), while 30-day readmission rate to surgical services was 5% higher in the SDT group versus the PST group (P<0.05), but frequency of 30-day readmissions was lower (1.1 vs 1.6 times, P<0.05). LOS in medical services was not different between the two groups, but it was significantly longer in surgical services in SDT (P<0.05). However, LOS was significantly lower in patients who were seen by SDT during the first 24 hours of admission compared with those who were seen after that (4.7 vs 6.1 days, P<0.001). Compliance to follow-up was higher in the SDT group. These changes were translated into considerable cost saving. CONCLUSIONS: Inpatient diabetes management by an SDT significantly reduces 30-day readmission rate to medical services, reduces inpatient diabetes cost, and improves transition of care and adherence to follow-up. SDT consultation during the first 24 hours of admission was associated with a significantly shorter hospital LOS.
RESUMO
CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.
Assuntos
Anticorpos Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sistemas de Liberação de Medicamentos/métodos , Pontos Quânticos/química , Receptor ErbB-2/antagonistas & inibidores , Ácido 3-Mercaptopropiônico/química , Animais , Compostos de Cádmio/química , Feminino , Ácido Fólico/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Receptor ErbB-2/química , Receptor ErbB-2/metabolismo , Compostos de Selênio/química , Succinatos/química , Sulfetos/química , Telúrio/química , Compostos de Zinco/químicaRESUMO
Radioactive iodine (RAI) ablation is a beneficial, adjuvant therapy for the management of differentiated thyroid cancer (DTC) after thyroidectomy. The goal of RAI is to destroy remnant thyroid and microscopic cancerous tissue. Radioactive iodine uptake is enhanced by elevating TSH levels and initiating a low iodine diet (LID) prior to ablation. An ideal LID should preferably not exceed 50 mcg/day of dietary iodine for 1-2 weeks, although the duration may be shortened to a week with a structured patient education programme. A pre-ablation spot urinary iodine concentration (UIC) of <100 mcg/l and/or a urinary iodine to creatinine ratio (UICR) of <100 mcg/gCr would support an adequate LID preparation. Hyponatraemia, most likely due to iatrogenic hypothyroidism, is a potential side effect associated with LID and occurs during and a few days after the LID. Although the overall incidence of hyponatraemia is low, patients at high risk (older age, female sex, use of thiazide diuretics) may benefit from serum sodium monitoring. The existing evidence on the impact of LID on RAI ablation has been largely inconsistent due to retrospective study designs and the lack of an objective measurement of urinary iodine levels. Future large prospective randomized control trials are needed to elucidate and confirm the crucial role of LID in achieving successful RAI ablation and greater disease-free survival in DTC.
Assuntos
Dieta , Radioisótopos do Iodo/uso terapêutico , Iodo/administração & dosagem , Neoplasias da Glândula Tireoide/dietoterapia , Neoplasias da Glândula Tireoide/radioterapia , Terapia Combinada , Humanos , Iodo/urina , Guias de Prática Clínica como Assunto , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do TratamentoRESUMO
CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.
Assuntos
Anticorpos Monoclonais/química , Neoplasias da Mama/diagnóstico por imagem , Ácido Fólico/química , Pontos Quânticos/química , Receptor ErbB-2/antagonistas & inibidores , Ácido 3-Mercaptopropiônico , Compostos de Cádmio/química , Fluorescência , Humanos , Microscopia Confocal , Coloração e Rotulagem , SulfetosRESUMO
Delivery of antigen through admixture formulation containing poly caprolactone (PCL) and aluminum phosphate was studied as a promising strategy to generate antigen specific immune response. The present study demonstrates the synergistic effect of admixture formulation of PCL with reduced aluminum (PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT) as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. On evaluation of the magnitude of efficacy for the proposed formulation by ELISA as well as challenge method, persistent and strong antibody response was obtained throughout the 180 day study period on storage at 5 ± 3 °C. In comparison to the aluminum phosphate based conventional tetanus vaccine, higher levels of IFN-γ and IL-4 were obtained with PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT, indicating the presence of cell mediated as well as humoral immune responses. Histopathology and serum biochemistry profile in mice further indicated the suitability of the proposed formulation. Percent adsorption/encapsulation of the antigen also increased to nearly 95% in the admixture formulation compared to 55% adsorption in the conventional tetanus vaccine. The present study established a useful baseline for designing biocompatible and effective delivery system for toxoid vaccines through judicious use of PCL based biodegradable nanoparticles in combination with aluminum phosphate.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Alumínio/química , Portadores de Fármacos , Poliésteres/química , Toxoide Tetânico/administração & dosagem , Animais , Imunidade Celular , Imunidade Humoral , Interferon gama/imunologia , Interleucina-4/imunologia , Camundongos , Nanopartículas/química , Potência de VacinaRESUMO
Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone-secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.
Assuntos
Síndrome de Cushing/diagnóstico , Síndrome de Cushing/metabolismo , Gerenciamento Clínico , Biomarcadores/análise , Biomarcadores/metabolismo , Diagnóstico Diferencial , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Saliva/química , Saliva/metabolismoRESUMO
Delivering peptides into cells targeting the undruggable oncoproteins is an emerging area in cancer therapeutics. Here we report a novel nanoparticle-based delivery system that can transport therapeutic cargos to the intracellular sites without the need for a cell transduction or penetration domain (CPP). In the present study, we have used iron oxide nanoparticles to deliver an oncopeptide, NuBCP-9, targeting the BCL-2 BH3 domain. Citric acid/2-bromo 2-methylpropanoic acid (CA/BMPA)-capped SPIONs were used to immobilize and deliver the NuBCP-9 peptide to the cancer cells without any noticeable off-target effects. Our results have demonstrated that NuBCP-9-SPIONs efficiently penetrate into cancer cells and bind to its intracellular target protein BCL-2. Moreover, significant inhibition of proliferation and substantial induction of cell death were observed when cancer cells were treated with NuBCP-9-SPIONs at different time intervals. Importantly, the IC50 values for killing of breast cancer cells with NuBCP-9-SPIONs were much lower compared to cells treated with the NuBCP-9 peptide linked with a CPP (Arg-8; NuBCP-9-R8). Molecular and biochemical analyses further supported that NuBCP-9-SPIONs killed breast cancer cells by apoptosis-mediated mechanisms. Furthermore, our data demonstrated that administration of NuBCP-9-SPIONs to mice bearing Ehrlich ascites tumors (EAT) was associated with loss of tumorigenicity and extensive apoptosis in tumor tissues. Taken together, these findings show that a non-CPP-tagged peptide can be successfully delivered to undruggable intracellular oncotargets using SPIONs.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Compostos Férricos , Nanopartículas/química , Oligopeptídeos , Animais , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Portadores de Fármacos , Feminino , Compostos Férricos/química , Compostos Férricos/farmacologia , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination.
Assuntos
Adjuvantes Farmacêuticos/química , Compostos de Alumínio/química , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Lactatos/química , Nanopartículas/química , Fosfatos/química , Polietilenoglicóis/química , Toxoide Tetânico/administração & dosagem , Animais , Anticorpos/sangue , Composição de Medicamentos , Sinergismo Farmacológico , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Tamanho da Partícula , Propriedades de Superfície , Toxoide Tetânico/efeitos adversos , Toxoide Tetânico/imunologiaRESUMO
BACKGROUND: Scarring represents a significant biomedical burden in clinical medicine. Mechanomodulation has been linked to scarring through inflammation, but until now a systematic approach to attenuate mechanical force and reduce scarring has not been possible. METHODS: The authors conducted a 12-month, prospective, open-label, randomized, multicenter clinical trial to evaluate abdominoplasty scar appearance following postoperative treatment with the embrace Advanced Scar Therapy device to reduce mechanical forces on healing surgical incisions. Incisions from 65 healthy adult subjects were randomized to receive embrace treatment on one half of an abdominoplasty incision and control treatment (surgeon's optimal care methods) on the other half. The primary endpoint for this study was the difference between assessments of scar appearance for the treated and control sides using the visual analogue scale scar score. RESULTS: Final 12-month study photographs were obtained from 36 subjects who completed at least 5 weeks of dressing application. The mean visual analogue scale score for embrace-treated scars (2.90) was significantly improved compared with control-treated scars (3.29) at 12 months (difference, 0.39; 95 percent confidence interval, 0.14 to 0.66; p = 0.027). Both subjects and investigators found that embrace-treated scars demonstrated significant improvements in overall appearance at 12 months using the Patient and Observer Scar Assessment Scale evaluation (p = 0.02 and p < 0.001, respectively). No serious adverse events were reported. CONCLUSIONS: These results demonstrate that the embrace device significantly reduces scarring following abdominoplasty surgery. To the authors' knowledge, this represents the first level I evidence for postoperative scar reduction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
Assuntos
Abdominoplastia , Bandagens , Cicatriz/prevenção & controle , Cuidados Pós-Operatórios/instrumentação , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Cicatriz/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fotografação , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Resultado do Tratamento , Escala Visual Analógica , Cicatrização , Adulto JovemRESUMO
A digital micromirror device (DMD) is an array of individually switchable mirrors that can be used in many advanced optical systems as a rapid spatial light modulator. With a DMD, several implementations of confocal microscopy, hyperspectral imaging, and fluorescence lifetime imaging can be realized. The DMD can also be used as a real-time optical processor for applications such as the programmable array microscope and compressive sensing. Advantages and disadvantages of the DMD for these applications as well as methods to overcome some of the limitations will be discussed in this article. Practical considerations when designing with the DMD and sample optical layouts of a completely DMD-based imaging system and one in which acousto-optic deflectors (AODs) are used in the illumination pathway are also provided.