Targeted delivery of therapeutics through the use of nanoparticles (NPs) has emerged as a promising method that increases their efficacy and reduces their side effects. NPs can be tailored to localize to selective tissues through conjugation to ligands that bind cell-specific receptors. Although the vast majority of nanodelivery platforms have focused on cancer therapy, efforts have begun to introduce nanotherapeutics to the fields of immunology as well as transplantation. In this review, we provide an overview from a clinician’s perspective of current nanotherapeutic strategies to treat solid organ transplants with NPs during the time interval between organ harvest from the donor and placement into the recipient, an innovative technology that can provide major benefits to transplant patients. The use of ex vivo normothermic machine perfusion (NMP), which is associated with preserving the function of the organ following transplantation, also provides an ideal opportunity for a localized, sustained, and controlled delivery of nanotherapeutics to the organ during this critical time period. Here, we summarize previous endeavors to improve transplantation outcomes by treating the organ with NPs prior to placement in the recipient. Investigations in this burgeoning field of research are promising, but more extensive studies are needed to overcome the physiological challenges to achieving effective nanotherapeutic delivery to transplanted organs discussed in this review.
Oral cancer prevalence is increasing at an alarming rate worldwide, especially in developing countries which lack the medical infrastructure to manage it. For example, the oral cancer burden in India has been identified as a public health crisis. The high expense and logistical barriers to obtaining treatment with surgery, radiotherapy and chemotherapy often result in progression to unmanageable late stage disease with high morbidity. Even when curative, these approaches can be cosmetically and functionally disfiguring with extensive side effects. An alternate effective therapy for oral cancer is a light based spatially-targeted cytotoxic therapy called photodynamic therapy (PDT). Despite excellent healing of the oral mucosa in PDT, a lack of robust enabling technology for intraoral light delivery has limited its broader implementation. Leveraging advances in 3D printing, we have developed an intraoral light delivery system consisting of modular 3D printed light applicators with pre-calibrated dosimetry and mouth props that can be utilized to perform PDT in conscious subjects without the need of extensive infrastructure or manual positioning of an optical fiber. To evaluate the stability of the light applicators, we utilized an endoscope in lieu of the optical fiber to monitor motion in the fiducial markers. Here we showcase the stability (less than 2 mm deviation in both horizontal and vertical axis) and ergonomics of our applicators in delivering light precisely to the target location in ten healthy volunteers. We also demonstrate in five subjects with T1N0M0 oral lesions that our applicators coupled with a low-cost fiber coupled LED-based light source served as a complete platform for intraoral light delivery achieving complete tumor response with no residual disease at initial histopathology follow up in these patients. Overall, our approach potentiates PDT as a viable therapeutic option for early stage oral lesions that can be delivered in low resource settings.
Heart failure (HF) is associated with pathological remodeling of the myocardium, including the initiation of fibrosis and scar formation by activated cardiac fibroblasts (CFs). Although early CF-dependent scar formation helps prevent cardiac rupture by maintaining the heart’s structural integrity, ongoing deposition of the extracellular matrix in the remote and infarct regions can reduce tissue compliance, impair cardiac function, and accelerate progression to HF. In our study, we conducted mass spectrometry (MS) analysis to identify differentially altered proteins and signaling pathways between CFs isolated from 7 day sham and infarcted murine hearts. Surprisingly, CFs from both the remote and infarct regions of injured hearts had a wide number of similarly altered proteins and signaling pathways that were consistent with fibrosis and activation into pathological myofibroblasts. Specifically, proteins enriched in CFs isolated from MI hearts were involved in pathways pertaining to cell–cell and cell–matrix adhesion, chaperone-mediated protein folding, and collagen fibril organization. These results, together with principal component analyses, provided evidence of global CF activation postinjury. Interestingly, however, direct comparisons between CFs from the remote and infarct regions of injured hearts identified 15 differentially expressed proteins between MI remote and MI infarct CFs. Eleven of these proteins (Gpc1, Cthrc1, Vmac, Nexn, Znf185, Sprr1a, Specc1, Emb, Limd2, Pawr, and Mcam) were higher in MI infarct CFs, whereas four proteins (Gstt1, Gstm1, Tceal3, and Inmt) were higher in MI remote CFs. Collectively, our study shows that MI injury induced global changes to the CF proteome, with the magnitude of change reflecting their relative proximity to the site of injury.
The ability of drug-eluting stent (DES) to inhibit intimal proliferation has resulted in a massive increase in their usage over the years. However, it is known that the application of DES can alter the normal cascade of vascular healing, resulting in delayed endothelialisation with risk of vascular complications. Coronary artery aneurysms (CAN) are defined as more than 50% dilatation of the coronary artery compared to the reference vessel diameter with the reported incidence after percutaneous intervention (PCI) being only around 0.35 to 6.0%. Previously, CAN had been reported with the use of bare metal stent secondary to stretch, stent fracture and dissection. However, recently, increasing number of cases have been reported describing CAN after DES implantation. To the best of the authors' knowledge, they present the first case from Pakistan of a left anterior descending coronary artery aneurysm after DES implantation treated successfully with stenting under intravascular ultrasound guidance.
With the scientific advancements in the management of malignant diseases, the treatment is expensive and bears high morbidity in term of oral mucositis. It is a debilitating condition and has been researched extensively for its pathogenesis and treatment. Various treatment options include barrier forming, mucosal protectants, mouth rinses, growth factors, lasers and midline-sparing procedures. Some agents are used locally while others are administered systemically. Despite the availability of a wide range of treatment options for mucositis, a cost-effective treatment is yet to be evolved.
Objective: To study the outcomes of left main percutaneous coronary artery (LMCA) revascularisation. Study Design: A descriptive study. Place and Duration of Study: The Aga Khan University Hospital (AKUH), Karachi, from February till July 2016. Methodology:The study included all adult patients aged 18 years or more, who underwent percutaneous LMCA revascularisation at study centre from April 2006 till April 2015. In-hospital outcomes were ascertained of patients via charts along with telephonic follow-up for outcome ascertainment at 1-year and 5-year. Results were expressed in terms of means and standard deviation for quantitative variables and percentages for qualitative variables. Results: Of the 86 patients, the mean age was 66.05 ±12.6 years and 69% (59 cases, n=86) of them were males. Sixteen (18.6%) patients presented with cardiogenic shock and 17.4% (15 cases, n=86) required mechanical ventilation upon arrival. Among the 86 patients, 23.3% (20 patients, n=86) underwent PCI because of unstable condition for CABG and refusal by the surgeons. Mean follow up time for participants was 40.5 ±25.7 months with mean length of hospital stay of 4.36 ±2.4 days. In-hospital mortality was 12.8%, while mortality at 1-year and at mean follow-up was 7.3% and 6.9%, respectively. Conclusion: LM percutaneous coronary intervention is a viable option for patients who are hemodynamicaly unstable and require urgent revascularisation or for patients denying bypass surgery due to other reasons in Pakistan. Prospective studies in future may be required to evaluate the role of PCI for LM lesions in elective setting in contrast to existing treatment options.
Please cite this article: Hussain B, Sultan F. A rare cardiac manifestation of Brucellosis. J Rare Cardiovasc Dis. 2017; 3(4): xx-xx; doi: http://dx
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