Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.     

Rabies surveillance in the United States during 1997

In 1997, 49 states, the District of Columbia, and Puerto Rico reported 8,509 cases of rabies in nonhuman animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 93% (7,899) were wild animals, whereas 7% (610) were domestic species. The total number of reported cases increased 19.4% from that of 1996 (7,128 cases). Increases were apparent in each of the major species groups, with the exception of cattle. The relative contributions of these groups to the total reported for 1997 were as follows: raccoons (50.5%; 4,300 cases), skunks (24.0%; 2,040), bats (11.3%; 958), foxes (5.3%; 448), cats (3.5%; 300), dogs (1.5%; 126), and cattle (1.4%; 122). The 958 cases of rabies reported in bats represented a 29.3% increase over the total reported for 1996 and the greatest number reported since 1984, with cases reported by 46 of the 48 contiguous states. The epizootic of rabies in raccoons expanded into Ohio in 1997 and now includes 19 states and the District of Columbia. Thirteen states, where rabies in raccoons is enzootic, reported increases over 1996 in total numbers of reported cases. New York (1,264 cases), North Carolina (879), Virginia (690), and Maryland (619) reported the greatest numbers of cases [corrected]. Five states reported increases that exceeded 50%, compared with cases reported in 1996: Ohio (673.3%; 15 cases in 1996 to 116 in 1997). Massachusetts (144.3%; 115 to 281), South Carolina (97.9%; 96 to 190), Connecticut (97.4%; 274 to 541), and Maine (86.3%; 131 to 244). Cases of rabies associated with foci of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas continued to decline, with this state reporting 78.3% fewer rabid foxes (13 cases), 26.7% fewer rabid dogs (11), and 63.2% fewer rabid coyotes (7) during 1997, compared with 1996. Reported cases of rabies in cats (300) and dogs (126) increased 12.8% and 13.5%, respectively, whereas cases in cattle (122) decreased by 6.9%. Thirty states, the District of Columbia, and Puerto Rico reported increases in rabies in animals during 1997, compared with decreases reported by 31 states and the District of Columbia in 1996. One state (Mississippi; 5 cases) remained unchanged. Hawaii was the only state that did not report a case of rabies in 1997. Four indigenously acquired cases of rabies reported in human beings were the result of infection with rabies virus variants associated with bats.     

Angioplasty and primary stenting of the subclavian, innominate, and common carotid arteries in 83 patients

A new macrocyclic of the bis(benzylisoquinoline) alkaloid family, d-(+)-tubocurarine chloride (DTC), has been evaluated as a chiral selector for the separation of optical isomers of organic carboxylates using capillary electrophoresis (CE). The pertinent physicochemical properties, such as absorption spectrum, isoionic point, and solution conformation, of DTC were determined. The effects of varying such experimental parameters as DTC concentration, pH, and methanol content in the running buffer were assessed. CE separation of the enantiomers of 18 different compounds was achieved using DTC as the chiral selector under optimized background electrolytic conditions.     

Assessing the forms and functions of aggression using self-report: Factor structure and invariance of the Peer Conflict Scale in youths.

This study examined the structure of a self-report measure of the forms and functions of aggression in 855 adolescents (582 boys, 266 girls) aged 12 to 19 years recruited from high school, detained, and residential settings. The Peer Conflict Scale (PCS) is a 40-item measure that was developed to improve upon existing measures and provide an efficient, reliable, and valid assessment of four dimensions of aggression (i.e., reactive overt, reactive relational, proactive overt, and proactive relational) in youths. Confirmatory factor analyses showed that a 4-factor model represented a satisfactory solution for the data. The factor structure fit well for both boys and girls and across high school, detained, and residential samples. Internal consistency estimates were good for the 4 factors, and they showed expected associations with externalizing variables (i.e., arrest history, callous-unemotional traits, and delinquency). Reactive and proactive subtypes showed unique associations consistent with previous literature. Implications for the use of the PCS to assess aggression and inform intervention decisions in diverse samples of youths are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of acute progesterone administration upon responses to acute psychosocial stress in men.

Animal studies suggest that neuroactive steroids, in particular progesterone and its metabolites, have stress-dampening effects. However, few studies have explored these effects in humans. In this study, we investigated the effects of acute progesterone administration on responses to the Trier Social Stress Test (TSST). Healthy men participated in the TSST 3.5 hrs after intramuscular injection of 0, 50, or 100 mg progesterone (N = 16, 14, and 14). We measured cardiovascular (heart rate, blood pressure), hormonal (plasma adrenocorticotrophic hormone, cortisol, and noradrenaline), and subjective (e.g., anxiety, arousal) responses to stress in the three groups. Before the TSST, progesterone injections increased plasma levels without altering physiological or subjective states. Stress produced its expected physiological and subjective effects among placebo-treated individuals. Progesterone 50 mg attenuated peak increases in plasma cortisol and reduced changes in negative mood and alertness after stress, yet it increased plasma noradrenaline and systolic blood pressure. Progesterone 100 mg also attenuated stress-induced increases in alertness and arousal, yet it potentiated stress-induced increases in diastolic pressure. Thus, progesterone dampened some of the psychological effects of stress but produced inconsistent effects on physiological stress responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversible simulation of bipartite product Hamiltonians

Consider two quantum systems A and B interacting according to a product Hamiltonian H=H/sub A//spl ominus/H/sub B/. We show that any two such Hamiltonians can be used to simulate each other reversibly (i.e., without efficiency losses) with the help of local unitary operations and local ancillas. Accordingly, all nonlocal features of a product Hamiltonian - including the rate at which it can be used to produce entanglement, transmit classical or quantum information, or simulate other Hamiltonians - depend only upon a single parameter. We identify this parameter and use it to obtain an explicit expression for the entanglement capacity of all product Hamiltonians. Finally, we show how the notion of simulation leads to a natural formulation of measures of the strength of a nonlocal Hamiltonian.     

Differentiation of the surface topographies of pharmaceutical excipient compacts

The comparison of conventional surface metrology and area-scale fractal parameters to differentiate the surface topography of pharmaceutical excipient compacts and preliminary investigation of scale-based correlations with excipient properties were performed. The determination and selection of the most appropriate surface topography parameters is important in optimizing the design and quality of industrial processes and products. The surfaces of three types of excipient compacts (microcrystalline cellulose (MCC), spray dried lactose (SDL), and dibasic calcium phosphate dihydrate (DCPD)) were characterized with a non-contact optical surface profilometer. A statistical F-test matrix was used to rank and quantify the ability of conventional surface texture parameters: Sa, Sq, St, Ssk, Sku, and the fractal parameters: relative area, Asfc (complexity) and SRC (smooth–rough crossover), to differentiate the surfaces of the compacts. Based on this statistical analysis and area-scale plots generated from profilometer data, it was found that most of the conventional parameters were suitable for distinguishing the surfaces. The F-test applied to the relative areas as a function of scale also indicated the ranges of scales over which the differentiation was possible. MCC–SDL and DCPD–SDL material pairs were able to be differentiated between scales of 10 and 10,000 μm², however, MCC–DCPD pairs were only differentiable between 300 and 2000 μm². A new method was established for illustrating the scale-based correlations, using the product of the regression coefficient and the normalized slope. The correlations between the fractal parameters and the properties of the excipients, including brittle fracture and indentation hardness, gave plausible explanations for the similarities between certain excipients, supporting a phenomenological understanding of the behavior of excipient compacts and their surfaces.     

Regulation of expression of epidermal growth factor receptors in gonadotropes by epidermal growth factor and estradiol: studies in cycling female rats

Changes in expression of epidermal growth factor (EGF) receptors by gonadotropes parallel those of GnRH receptors. Gonadotropes increase their expression of EGF receptors (EGFR) during diestrus to reach a peak on the morning of proestrus. This is followed by a decline in expression to reach a nadir by estrus. We hypothesized that regulatory factors that stimulate changes in GnRH receptors might mediate the same changes in EGFR. To test this hypothesis, pituitary cells were collected from cycling rats and grown overnight in media with or without serum, 100 pM estradiol, or 60 ng/ml activin. On the next day, some of the cultures were further stimulated with 1 nM GnRH (4 h). The cells were then dual-labeled for EGFR and LHbeta or FSHbeta antigens and analyzed for their content of EGFR and gonadotropins. Neither activin nor estradiol increased percentages of cells with gonadotropin antigens and EGFR. Estradiol decreased percentages of cells with EGFR and LH in proestrous rats and those with EGFR and FSH in diestrous rats. The estradiol-mediated decline in EGFR expression during proestrus is similar to that seen when GnRH receptors are studied. Serum containing media alone increased percentages of LH and FSH cells with EGFR in populations from estrous or metestrous rats. Therefore, further experiments were conducted to learn if serum factors or EGF might be a regulator. Removal of serum from the growth media did not prevent the increase in percentages of LH cells with EGFR over the 18-h growth period. However, removal of serum did prevent the increased percentages of FSH cells with EGFR. Similarly, adding 1:100 anti-EGF to the serum containing media did not affect expression of EGFR by LH cells. However, it did cause a 27% decrease in percentages of FSH cells with EGFR. Finally, when 10 ng/ml EGF was added to metestrous populations in serum-free media there was a 1.4-1.5-fold increase in percentages of LH or FSH cells with EGFR. Collectively, these studies show that EGF receptors are not stimulated in gonadotropes by the same hormones that up-regulate GnRH receptors. Furthermore, EGF itself may be among the factors that up regulate EGFR in gonadotropes. EGF receptors may be down-regulated by estradiol during proestrus, but the effect is limited to LH cells. Finally, EGF's differential effects on LH and FSH cells suggests that it may selectively act on monohormonal gonadotropes. EGF receptors may be a marker for a unique subset of developing gonadotropes.