We studied the integrity of the rotator cuff in both dominant and non-dominant shoulders of 90 asymptomatic adults between the ages of 30 and 99 years using ultrasound. The criteria for diagnosis had been validated on unembalmed cadaver specimens. We found no statistically significant difference in the incidence of impingement findings between dominant and non-dominant arms or between genders. The prevalence of partial-or full-thickness tears increased markedly after 50 years of age: these were present in over 50% of dominant shoulders in the seventh decade and in 80% of subjects over 80 years of age. Our results indicate that rotator-cuff lesions are a natural correlate of ageing, and are often present with no clinical symptoms. Treatment should be based on clinical findings and not on the results of imaging. J Bone Joint Surg [Br] l995:77-B:296-8.

Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment.We administered 198 Au-radio-labelled monodisperse, negatively charged GNP of five different sizes (1.4, 5, 18, 80, 200nm) and 2.8nm GNP with opposite surface charges by intravenous injection into rats. After 24 h the biodistribution of the GNP was quantitatively measured by gamma-spectrometry.The size and surface charge of GNP strongly determine the biodistribution. Most GNP accumulated in the liver increased from 50% of 1.4nm GNP to > 99% of 200nm GNP. In contrast, there was little size dependent accumulation of 18nm to 200nm GNP in most other organs. However, for GNP between 1.4nm and 5nm the accumulation increased sharply with decreasing size; i.e. a linear increase with the volumetric specific surface area. The differently charged 2.8nm GNP led to significantly different accumulations in several organs.We conclude that the alterations of accumulation in the various organs and tissues, depending on GNP size and surface charge, are mediated by dynamic protein binding and exchange. A better understanding of these mechanisms will improve drug delivery and dose estimates used in risk assessment.

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ.

Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of 198Au-radio-labelled monodisperse, well-characterized, negatively-charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1-h, 3-h, and 24-h the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows, as AuNP get smaller, they are more likely to cross the air-blood-barrier (ABB) depending strongly on the inverse diameter d−1 of their gold core; i.e. their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d−1 relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP which had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood and excretion via urine further declined with d−1 of AuNP core. Translocation of 5, 18 and 80 nm AuNP is virtually complete after 1-h, while 1.4 nm AuNP continue to translocate until 3-h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge.

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and V-radiolabeled [V]TiO nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [V]TiO-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [V]TiO-nanoparticle doses in the range of 30-80 μg•kg bodyweight, making use of the high sensitivity of the radiotracer technique. The [V]TiO-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for V-ions not bound to TiO-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [V]TiO-nanoparticle organ concentrations present in liver (0.09 ng•g), lungs (0.10 ng•g), kidneys (0.29 ng•g), brain (0.36 ng•g), spleen (0.45 ng•g), uterus (0.55 ng•g) and skeleton (0.98 ng•g). Since chronic, oral uptake of TiO particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [V]TiO-nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ largely, IV-injection is not an adequate surrogate for assessing the biokinetics after oral exposure to TiO nanoparticles.