Angiotensin II and insulin induce growth of ciliary artery smooth muscle: effects of AT1/AT2 antagonists

PURPOSE: Abnormal growth of smooth muscle cells (SMCs) in small arteries of the eye is associated with hypertension and diabetes, and the complications that they induce. Migration and proliferation of SMCs into the intima are primary mechanisms involved in neointima formation. In aortic SMCs, angiotensin II (AII)-induced proliferation is inhibited by angiotensin type 1 (AT1) receptor antagonist. However, in small artery SMCs, in particular in the circulation of the eye, the effects of AII on migration and proliferation are unknown. METHODS: The effects of AII (10(-6) to 10(-10) M) on migration and proliferation of growth-arrested SMCs of porcine ciliary arteries were studied in the presence and absence of insulin (5 x 10(-10) M) by assaying DNA synthesis (3H-thymidine incorporation), cell number, and movement of SMCs across the membrane of a modified Boyden chamber. RESULTS: In the absence of insulin, only high concentrations (10(-6) to 10(-8) M) of AII induced DNA synthesis and increased cell number (P < 0.05); however, in the presence of insulin (5 x 10(-10) M), AII induced DNA synthesis and cell number at low concentrations (10(-10) M) and in a concentration-dependent manner (P < 0.05). In contrast to proliferation, AII induced SMC migration in a concentration-dependent manner in the absence of insulin (P < 0.05). The AT1 antagonist CGP48933 (10(-8) to 10(-12) M), but not the AT2 antagonist CGP42112 (10(-8) to 10(-12) M), inhibited AII (10(-8) M)-induced proliferation and migration in a concentration-dependent manner (P < 0.05). CONCLUSIONS: Our results suggest that AII is a potent mitogen for SMCs of ophthalmic arteries, an effect that is enhanced in the presence of insulin, and that it may be an important contributor to structural vascular changes in the ophthalmic circulation in hypertension associated with non-insulin dependent diabetes. The inhibition of AII-induced growth by an AT1 antagonist suggests that these drugs may be important therapeutic tools to prevent structural vascular changes in the ophthalmic vasculature under these conditions.     

Substance abuse issues in cancer patients. Part 2: Evaluation and treatment

The relationship between the therapeutic use of potentially abusable drugs for symptom control and the multifaceted nature of abuse and addiction is extremely complex. Research is only beginning to elucidate the nature of this relationship and its clinical implications. At present, practical management is based primarily on clinical experience and anecdotal observations. In part I of this two-part series (published last month), the authors explored the epidemiology of substance abuse in the cancer population, provided definitions of addiction and abuse appropriate for the oncology setting, and offered guidelines for the assessment of aberrant drug-taking behavior. In this second part, the authors provide recommendations for the evaluation and treatment of patients with cancer who have a history of substance abuse. Suggested therapeutic goals are outlined, and plans for inpatient and outpatient management and detailed.     

A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils

Digestion of blood within the mosquito midgut is mediated primarily by a series of proteases, and several previous studies have described protease activity within homogenates of the midgut of the malaria vector Anopheles stephensi. We have expanded on these previous data by resolving protease isoforms from the midgut as well as the hemolymph of adult An. stephensi mosquitoes via gel electrophoresis and zymography. Using this procedure, we have been able to identify multiple isozymes of trypsin, chymotrypsin, and aminopeptidase. We were able to detect an increase in the intensity of some of these protease bands plus the appearance of new bands 24 hr after mosquitoes had taken a blood meal. Furthermore, we detected 2 endogenous trypsin isozymes within the hemolymph. There was no upregulation of these hemolymph isozymes after a blood meal, thus suggesting that they may not be involved in digestion of the blood meal by the mosquito.     

Essential Oil of <Emphasis Type="Italic">Artemisia scoparia</Emphasis> Inhibits Plant Growth by Generating Reactive Oxygen Species and Causing Oxidative Damage

We investigated the chemical composition and phytotoxicity of the essential oil extracted from leaves of Artemisia scoparia Waldst. et Kit. (red stem wormwood, Asteraceae). GC/GC-MS analyses revealed 33 chemical constituents representing 99.83% of the oil. The oil, in general, was rich in monoterpenes that constitute 71.6%, with β-myrcene (29.27%) as the major constituent followed by (+)-limonene (13.3%), (Z)-β-ocimene (13.37%), and γ-terpinene (9.51%). The oil and β-myrcene were evaluated in a dose–response bioassay under laboratory conditions for phytotoxicity against three weeds—Avena fatua, Cyperus rotundus, and Phalaris minor. A significant reduction in germination, seedling growth, and dry matter accumulation was observed in the test weeds. At the lowest treatment of 0.07 mg/ml Artemisia oil, germination was reduced by 39%, 19%, and 10.6% in C. rotundus, P. minor, and A. fatua, respectively. However, the inhibitory effect of β-myrcene was less. In general, a dose-dependent effect was observed and the growth declined with increasing concentration. Among the three weeds, the inhibitory effect was greatest on C. rotundus, so it was selected for further studies. We explored the explanation for observed growth inhibition in terms of reactive oxygen species (ROS: lipid peroxidation, membrane integrity, and amounts of conjugated dienes and hydrogen peroxide)-induced oxidative stress. Exposure of C. rotundus to Artemisia oil or β-myrcene enhanced solute leakage, indicating membrane disintegration. There were increased levels of malondialdehyde and hydrogen peroxide, indicating lipid peroxidation and induction of oxidative stress. We conclude that Artemisia oil inhibits plant root growth through generation of ROS-induced oxidative damage.     

Correlation of Mechanical Properties with Diameter and Cooling Rate of 1080 Wire-Rod

More than 540 heats of 1080 wire-rod were statistically analyzed by regression analyses to see whether tensile strength and percent reduction in area (%RA) relate to wire-rod diameter and composition. As diameter increases from 5.6 to 12.7 mm, the trend in %RA shows a decrease with negligible effect on the trend of the tensile strength. It was found that the estimated cooling rate at 700 °C during controlled cooling is responsible for the “diameter effect.” The effect of composition on %RA is minor when contrasted to the “diameter effect.” In particular, the effect of the concentrations of the residual elements on %RA within the compositional range studied is negligible.     

Robust Higher Order Potentials for Enforcing Label Consistency

This paper proposes a novel framework for labelling problems which is able to combine multiple segmentations in a principled manner. Our method is based on higher order conditional random fields and uses potentials defined on sets of pixels (image segments) generated using unsupervised segmentation algorithms. These potentials enforce label consistency in image regions and can be seen as a generalization of the commonly used pairwise contrast sensitive smoothness potentials. The higher order potential functions used in our framework take the form of the Robust P ⁿ model and are more general than the P ⁿ Potts model recently proposed by Kohli et al. We prove that the optimal swap and expansion moves for energy functions composed of these potentials can be computed by solving a st-mincut problem. This enables the use of powerful graph cut based move making algorithms for performing inference in the framework. We test our method on the problem of multi-class object segmentation by augmenting the conventional crf used for object segmentation with higher order potentials defined on image regions. Experiments on challenging data sets show that integration of higher order potentials quantitatively and qualitatively improves results leading to much better definition of object boundaries. We believe that this method can be used to yield similar improvements for many other labelling problems.     

Some relationships between skills in word-category recall and factors in adults' aphasia

It has long been recognized that a basic dimension to the lexical organization of the brain is semantic, and some brain mapping studies have indicated that the brain fields are distinctly different from some grammatical classes. Findings from the present investigation showed consistent relationships between 29 aphasic adults' performances on tasks involving graphic and gestural skills and those involving sequential recall of spoken words from different word categories. Each adult received the Porch Index of Communication Abilities which relies upon the physical manipulation of objects to assess verbal, gestural, and graphic abilities. Scores on a test requiring recall of word strings of nouns, verbs, adverbs, adjectives, or prepositions were used to predict the subscale scores from the Graphic and Gestural factors of the index. Recall scores for verb and preposition were predictive of the aphasic subjects' performances on the Graphic subscale, and noun and preposition scores were predictors of subjects' scores on the Gestural subscale. The results are related to other research showing that verb and preposition skills are predictive of fine motor abilities of children with communication disorders and brain-mapping studies. Some discussion centers on possible overlapping functions of brain activity involving word categories, language, and fine motor skills.