Sub-cellular accumulation of magnetic nanoparticles in breast tumors and metastases

In this study, the sub-cellular accumulation of superparamagnetic iron oxide nanoparticles (SPIONs) in breast tumors and peripheral organs were investigated. MNPs were conjugated with luteinizing hormone releasing hormone (LHRH), whose receptors are expressed by most types of breast cancer cells. After the nanoparticles were injected into female nude mice bearing MDA-MB-435S.luc tumors, the mice were sacrificed to collect tumors and peripheral organs for biological and TEM analyses. LHRH conjugated SPIONs (LHRH- SPIONs) were found to accumulate in cancer cells, mainly in the primary tumors and the metastatic lungs, where they aggregated to form clusters. In contrast, most of the unconjugated SPIONs were collected in the liver cells. The results suggest that LHRH- SPIONs can be used to target cancer cells in the primary breast tumors and the lung metastases. TEM is also shown to be a useful tool for the studies of sub-cellular distributions of SPIONs in tumors and tissues.     

Cellular senescence in the glaucomatous outflow pathway

The mechanisms responsible for the progressive malfunction of the trabecular meshwork (TM)-Schlemm's canal (SC) conventional outflow pathway tissue in primary open angle glaucoma (POAG) are still not fully understood. To determine whether POAG is characterized by an accumulation of senescent cells, similar to what has been described in other diseases, we have compared the levels of the senescence marker senescence-associated-beta-galactosidase (SA-beta-gal) in the outflow pathway cells of POAG and age-matched control donors. POAG donors demonstrated a statistically significant fourfold increase in the percentage of SA-beta-gal positive cells. These results suggest a potential role for cellular senescence in the pathophysiology of the outflow pathway.     

A morphologic study of the vasculature of malignant gliomas using thick celloidin sections and alkaline phosphatase stain

The combination of 100 microm thick celloidin sections and alkaline phosphatase (AP) enzyme histochemistry of the vascular endothelium offers a greatly enhanced, 3D morphologic perspective and reveals intricate details of the vasculature of brain. A study of tumor specimens obtained at craniotomy from 6 patients with glioblastomas, 1 with anaplastic oligodendroglioma and 1 with juvenile pilocytic astrocytoma was undertaken using this technique. Five of the 6 glioblastomas, the anaplastic oligodendroglioma and the low-grade astrocytoma specimen showed uniform staining of afferent tumor blood vessels. In the glioblastomas, newly formed vessels formed dense, festooned networks at the advancing edges of the tumor. Feeding arteries entered the tumor at the junction between the edge of the tumor and adjacent brain or meninges and proceeded to form striking, coiled vessels and smaller branches. The density of both small arteries and veins was greatly increased within the tumor although there was much variability. Disordered arborization, arteriole to venous and arteriole to arteriole shunts were observed, leading to a situation where arteries connected directly to veins. In necrotic areas, there were often no AP-stained vessels. In many places, arterioles and capillaries were lacking. Numerous AP-negative veins of various sizes drained the tumors. Glomeruloid proliferations were presumptively identified as focal stain smudges or clusters of capillaries arising from nearby vascular channels. Increased alkaline phosphatase staining and/or focal new vessels were seen outside necrotic areas. The pilocytic astrocytoma and the oligodendroglioma showed less dense vascularity and no formation of the focal festoons of vessels shown by the glioblastomas. This technique may be useful for the study of tumor angiogenesis and to evaluate vascularity in experimental and human brain tumors after various therapies.     

A combined hematoxylin-eosin, alkaline phosphatase and high-resolution microradiographic study of lacunes.

Lacunar infarcts (lacunes) are small, cystic lesions of the brain in patients with hypertension and/or diabetes. In order to improve our understanding of the relationship between lacunes and their blood vessels, the alkaline phosphatase (AP) technique of microvascular staining and high-resolution microradiography were employed in a three-dimensional study of 31 lacunes from 15 hypertensive subjects. A second aim was to compare the usefulness of the techniques with that of routine hematoxylin-eosin (HE) stain employed by previous investigators. Arteries were traced throughout their course. The lesions identified included intimal hyperplasia, hyalinization and atherosclerosis with variable narrowing and occasional occlusions. The small arterioles in the lacune cavities supplied adjacent intact brain. The AP technique clearly distinguished true lacunar infarcts from dilated perivascular spaces. AP and microradiography were superior to HE in showing the three dimensional details with far fewer sections. Four different types of relationships were observed between nutrient arteries and their lacunes, indicating that patterns of vascular involvement can be elucidated in brains of subjects dying with lacunar syndromes by using special techniques such as AP. Such patterns can be correlated with clinical risk factors such as hypercholesterolemia, hypertension etc., singly and in combination. Our data suggest that the natural history of lacunar infarcts may be changing in two ways--the number of lacunes per patient may be diminishing and white matter involvement may be increasing. Possible explanations for these changes are suggested.     

External argon laser choroidotomy for subretinal fluid drainage

Purpose: To evaluate the efficacy and safety of external argon laser choroidotomy for drainage of subretinal fluid (SRF) during scleral buckling procedures for the repair of rhegmatogenous retinal detachments. Methods: Fifty eyes of 50 consecutive patients presenting to a hospital-based retinal outpatient clinic with rhegmatogenous detachments underwent choroidotomy with argon endolaser for SRF drainage. The laser parameters used were 0.5 s duration and 0.8 W power. The primary outcome measures were successful drainage of SRF and incidence of complications. The drainage was considered successful if it was sufficient to complete the planned scleral buckling procedure. The extent of subretinal haemorrhage was graded. Results: The mean age of patients was 55 years (range 16–80 years). Successful drainage of SRF was obtained in 47 eyes (94%). The complications observed at the drainage site included subretinal haemorrhage of less than I disc diameter in six eyes (12%) and retinal perforation in one eye (2%). Conclusion: External argon laser choroidotomy appears to be an effective method of draining SRF in rhegmatogenous retinal detachments.     

Red cell phosphate metabolism in preterm infants with idiopathic respiratory distress syndrome

Phosphate metabolism was studied in twenty-one preterm infants with idiopathic respiratory distress syndrome during and after oxygen (O2) therapy using a hood. Plasma, red cell inorganic phosphate (Pi) and the red cell concentrations of organic phosphate metabolites ATP and 2,3-diphosphoglycerate were significantly lower in the sick infants when compared to controls of similar age and birthweight, and remained low even 24 h after cessation of therapy. Plasma cortisol levels were elevated at the onset of the disease and decreased to almost control levels by the end of O2 therapy while the values of plasma calcitonin did not show any difference from controls. Plasma creatinine phosphokinase and blood lactic acid levels followed the pattern of the control group with a small increase at the beginning of the study and decreasing thereafter. Several factors may be implicated in the cause of hypophosphatemia in these infants such as inadequate feeding, acidosis and hypercortisolaemia due to stress leading to phosphaturia.