Medial arterial calcification (MAC) is a common outcome in diabetes and chronic kidney disease (CKD). It occurs as linear mineral deposits along the degraded elastin lamellae and is responsible for increased aortic stiffness and subsequent cardiovascular events. Current treatments for calcification, particularly in CKD, are predominantly focused on regulating the mineral disturbance and other risk factors. Ethylene diamine tetraacetic acid (EDTA), a chelating agent, can resorb mineral deposits, but the systemic delivery of EDTA may cause side effects such as hypocalcemia and bone resorption. We have developed elastin antibody conjugated albumin nanoparticles that target only degraded elastin in vasculature while sparing healthy tissues. In this study, we tested a targeted nanoparticle-based EDTA chelation therapy to reverse CKD-associated MAC. Renal failure was induced in Sprague-Dawley rats by a high adenine diet supplemented by high P and Ca for 28 days that led to MAC. Intravenous delivery of DiR dye-loaded nanoparticles confirmed targeting to vascular degraded elastin and calcification sites within 24 hours. Next, EDTA-loaded albumin nanoparticles conjugated with an anti-elastin antibody were intravenously injected twice a week for two weeks. The targeted nanoparticles delivered EDTA at the site of vascular calcification and reversed mineral deposits without any untoward effects. Systemic EDTA injections or blank nanoparticles were ineffective in reversing MAC. Reversal of calcification seems to be stable as it did not return after the treatment was stopped for an additional four weeks. Targeted EDTA chelation therapy successfully reversed calcification in this adenine rat model of CKD. We consider that targeted NP therapy will provide an attractive option to reverse calcification and has a high potential for clinical translation.
Objectives Since the first known hieroglyphics showing the war trophy taking of the penis, the capacity of anatomical amputation has always been a nightmarish aspect of wars. War trophies were a prodigious aspect of war in preliterate societies and ancient Greece. Herodotus wrote that Scythian warriors would present to their king the heads of enemies to claim their share of plunder. We performed a literature search to identify instances of war-associated phallotomy in its historical perspective. Methods A review of the literature from primary military and secondary sources was undertaken to assess the aspects of warfare specific to trophy taken, its origins, and impact. Results Egyptian warriors were famed for collecting as many enemy phalluses as possible in the battle of Khesef-Tamahu. There is some evidence that they spared those enemies who were circumcised. Anthropological studies point to the practice of phallotomy in some indigenous peoples of the Americas. There are biblical accounts of phallotomy that specify foreskin status which themselves were also used for royal presentation. Phallotomy also appears to have been documented in African, Arabian, and Meospotomian cultures but continued in some form into the Second World War. Conclusions The barbarity of war may be eclipsed by additional atrocities inflicted by victor over the defeated with the collection of anatomical relics. Such war ‘trophies’ included the penis as an ultimate attempt to humiliate the vanquished
While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.
Primary renal angiosarcoma (AS) encompasses only 1% of soft tissue sarcomas, and it is seldom seen in literature. Because of its rarity, few risk factors for its development have been established. Due to lack of screening guidelines for kidney cancer, it is often found late when patients become symptomatic. We present the case of a male patient who presented with gross hematuria and flank pain and was discovered to have a large renal mass. Following successful resection, pathology showed it to be AS. The patient had a post-operative course complicated by two separate COVID-19 infections and expired 200 days after surgery. This case not only highlights an extremely rare renal cancer but also illustrates the challenges patients with complex medical issues faced in the era of COVID-19.
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