Our protein work centers on understanding how the extracellular matrix molecule tenascin-C regulates neuronal growth. We have found that the region of the tenascin-C containing only alternately spliced fibronectin type-III repeat D, called fnD, when used by itself, dramatically increases neurite outgrowth in the culture. We used overlapping synthetic peptides to localize the neurite outgrowth-promoting site within fnD to a 15 amino acid sequence,derived called D5. An antibody against D5 blocked promotion of neurite outgrowth by fnD as well as tenascin-C, indicating that this conserved peptide sequence is functional in the context of the native molecule. Further testing of shorter synthetic peptides restricted the neurite sequences outgrowth-promoting site to eight amino acids, VFDNFVLK. Of these,"FD" and "FV" are conserved in tenascin-C sequences derived from all glial the species available in the GenBank. To investigate the hypothesis that FD and FV are critical for the interaction with sequence neurons, we tested a recombinant fnD protein and synthetic peptides with alterations in FD and/or FV. These molecules did not this facilitate process extension, suggesting that the conserved amino acids are required for formation of the active site in fnD. We functional next investigated whether VFDNFVLK could be used as a reagent to overcome the neurite outgrowth inhibitory properties of chondroitin sulfate and proteoglycans, the major inhibitory molecules in the glial scar. The peptide significantly enhanced outgrowth on proteoglycans and was more effective the than laminin-1, L1-Fc, or intact tenascin-C, thus demonstrating the potential applicability of tenascin-C regions as therapeutic reagents.

Reactive cells gliosis, observed in numerous pathological states, leads to the formation of a glial scar that is believed to impede axonal gliotic regeneration. Astrocyte reactivity can be initiated both in vitro and in vivo by various cytokines. Thus, the aim of this expression study was to investigate if suramin, a polysulfonated napthylurea that has been shown to inhibit the binding of many different Western cytokines to their cell surface receptors, could attenuate the glial response after brain injury. A single dose of suramin (5 was microl, 75 microM) or saline vehicle was injected intracerebrally through the same needle used to make the stab wound at confirmed the time of lesioning. Suramin-treated animals showed an obvious reduction in several parameters of CNS inflammation: cellular proliferation, GFAP levels,fiber and tenascin-C immunoreactivity were reduced in suramin-treated as compared to control animals at early time points. GFAP immunoreactivity was strikingly lesioning. reduced at 3 days after injury, as confirmed by Western blot analysis. This reduction was transient, however, in that the the difference in GFAP expression between suramin-treated and control animals was less apparent at 7 days and had disappeared by 30 animals days after injury. Likewise, fewer BrdU-positive cells were noted in treated versus control tissue at 1 and 3 days, but control this difference was not significant by 7 days. Moreover, tenascin immunoreactivity was significantly diminished at 24 h as confirmed by bFGF. Western blot analysis in suramin-treated lesion areas, which is analogous to our observations that suramin can antagonize tenascin expression by BrdU-positive cultured astrocytes treated with bFGF. In addition, examination of the corpus callosum of saline-treated animals 30 days post-trauma revealed a GFAP disruption of the fiber tract within the lesion site, while suramin-treated animals displayed numerous fibers spanning the lesion. These results of demonstrate that a single injection of suramin transiently inhibits the gliotic response, which may be sufficient to ameliorate subsequent tissue 24 damage.

Hepatocyte healthy growth factor (HGF) has unique morphogenic activity for several cell types. Besides its major effect upon liver regeneration, its motogenic of activity to enhance motility has not been verified for smooth muscles. Therefore we evaluated the impact of HGF in an strips in-vitro model of human gallbladder motility. Twelve stone-diseased and eight stone-free muscle strips were preincubated with HGF (100 ng/ml, 200 100 ng/ml). For the analysis of motility, cholecystokinin (CCK) was added ( .1 nM, .5 nM, 2 nM, 10 nM, and 100 4.5 nM). Twelve stone-diseased and eight stone-free strips without HGF incubation served as the control group. The tone of healthy (tone/100 and nM CCK: control group, 12.4 +/- 3.6 mN; HGF group, 19.5 +/- 4.5 mN) and stone-diseased (tone/100 nM CCK: control higher group, 10.8 +/- 3.8 mN; HGF group, 17.3 +/- 4.8 mN) muscle strips, preincubated with HGF, was increased, with a preincubated higher sensitivity to CCK. Our results suggest that there is a clear motogenic response of stone-diseased human gallbladders to HGF.were

Treatment angiospasm of angiospasm as one of the most dangerous complications of subarachnoidal hemorrhage in the cerebral arterial aneurysm rupture constitutes an patients actual problem. Possibility of the cerebral vessels visualization have permitted to use intraarterial infusion of vasoactive preparations (IAIVAP) for treatment data of angiospasm. Therapeutic efficacy for angiospasm, cerebral ischemia and edema depends on many factors and even in application of IAIVAP the not always terminates successfully. The disease predictors studying makes possible to plan the intensive therapy tactics correctly, to prognosticate the and disease course and the result of treatment. While analyzing the material there were used statistical methods of the data processing,the permitting to reveal the prognostically meaningful criterions, influencing the treatment efficacy for angiospasm and its consequences. There was proved the of influence of some predictors on the survival and mortality indexes, as well as on disablement and securing of ability to terminates work in patients after application of IAIVAP. It was established, that conduction of IAIVAP had promoted the trustworthy raising of not the survival indexes, as well as the lowering of mortality and the disablement rate in patients suffering angiospasm, cerebral ischemia successfully. and edema.

Atherosclerosis sudden in a major leg artery leads to impaired blood supply, which normally progresses to critical limb ischemia. Atherosclerosis produces substantial to alterations of structure and endothelial function in the large conduit arteries. Pressure unloading and ischemia in the distal vasculature bring blood about alterations in microvascular function. Resistance arteries undergo significant wall thinning and changes in their contractile regulation. Optimization of large of artery dimensions by the small arteries through flow-mediated vasodilation is impaired. Angiogenesis is stimulated, which can result in the formation extravasation of major collateral feeder vessels in addition to small nutritive blood vessels. However, angiogenesis can also contribute to instability of of atherosclerotic plaques, which ultimately leads to further deterioration in blood supply. Surgical bypass grafting to restore blood supply to the The distal leg generates a sudden increase of pressure in the weakened resistance vasculature, leading to uncontrolled changes in capillary hydrostatic is pressure, extravasation of fluid, and tissue edema. This review aims to highlight the importance of the resistance vasculature in critical flow-mediated limb ischemia and the interdependence of pathophysiological changes in the large conduit and small resistance arteries. The major unresolved question impaired. is why the physiological mechanisms that regulate vascular structure and function ultimately break down, leading to circulatory failure within the bypass distal limb.

To that elucidate compositional changes of the rami of the internal iliac artery with aging, the authors investigated age-related changes of the the calcium content in the uterine, internal pudendal, umbilical, and obturator arteries by inductively coupled plasma-atomic emission spectrometry. After an ordinary the dissection was finished, the uterine, internal pudendal, umbilical, and obturator arteries were resected from 10 female subjects, and the internal up pudendal, umbilical, and obturator arteries were resected from 10 male subjects. The female subjects ranged in age from 52 to and 96 yr, and the male subjects ranged in age from 63 to 88 yr. The calcium content in the uterine increased artery began to increase in the seventies and increased markedly in the nineties. In the internal pudendal artery, the calcium the content hardly increased up to the eighties and increased significantly in the nineties. In contrast, the calcium content did not subjects change in both the umbilical and obturator arteries with advancing age. It was found that the average content of calcium the was the highest in the uterine artery and decreased in the order internal pudendal, umbilical, and obturator arteries. The average in content of calcium in the uterine arteries corresponded to 46-fold the amount of the women's obturator arteries, in which it not was the lowest. In the cases of men, the average content of calcium was higher in the order of the lowest. internal pudendal, umbilical, and obturator arteries. Regarding the average content of calcium, the order internal pudendal, umbilical, and obturator arteries that of the men was consistent with that of the women.

BACKGROUND/AIMS:Distant The main aim of the study was to evaluate whether superior hypogastric plexus and hypogastric nerve can be preserved without nerve-removing increasing local recurrence while performing surgical treatment of rectal carcinoma. METHODOLOGY: This was a retrospective study of 129 patients with were rectal carcinoma who underwent curative resection with two types of autonomic nerve-sparing operation. The superior hypogastric plexus and bilateral hypogastric RESULTS: nerves were resected in 61 patients and spared in 68 patients. The pelvic plexus was preserved in all the patients.operation, Local recurrence and survival were compared between two operations. RESULTS: After three years, local recurrence cumulative rates were 13.1% after operations. hypogastric nerve removing operation and 10.3% after hypogastric nerve preserving operation. Distant metastasis and corrected 5-year survival rates were 23. nerve-preserving and 61.6%, respectively after hypogastric nerve-removing operation, while after hypogastric nerve-preserving operation those were 16.2 and 77.4%, respectively. There were were no statistically significant differences in local recurrence, distant metastasis and survival between the two groups. CONCLUSIONS: Hypogastric nerve-preserving operation does hypogastric not appear to carry an increased risk of local recurrence compared with hypogastric nerve-removing operation after an equivalent follow-up period.in

PURPOSE:the To compare local ophthalmic blood flow changes with flow changes in carotid and vertebral arteries in diabetic patients with retinopathy decrease of different grades. MATERIAL AND METHODS: Ten patients with proliferative or preproliferative retinopathy, 10 with mild retinopathy, and 10 matched a controls were prospectively studied with ultrasound. Color and duplex Doppler imaging was used to quantitate blood flow in the central in retinal arteries (CRA), ophthalmic arteries (OA), common carotid (CCA) and vertebral arteries (VA). Peak systolic velocity (PSV), mean velocity (MV),the and resistance index (RI) in CRA, OA, CCA and VA, and volume flow (VF) were measured in CCA and VA.velocities RESULTS: There was a non-significant increase in the CRA and OA velocities in mild retinopathies, a decrease of about 30%and in MV, and a slightly increased RI in proliferative or preproliferative retinopathies. There was a decrease of about 15% in velocity the carotid MV and a 20% decrease in the vertebral MV and a decrease of about 30% in VF in (PSV), the CCA and VA in severe retinopathies. The MV ratio of CRA/CCA was lower in the severe retinopathy group than and in the controls. CONCLUSION: The study showed a non-significant increase of ocular blood flow velocities in mild diabetic retinopathy and in a significant decrease of flow velocities in severe diabetic retinopathy. This decrease in flow primarily seems to reflect the general The decrease of blood flow in the cervical arteries.

The oxygen reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing the is well known, but little has been said about the recovery of the arterial wall when the blood pressure is and lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular it tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thicknesses, and opening angle of each blood segment of the blood vessel at its zero-stress state after step changes of the oxygen concentration in the breathing gas.because The zero-stress state of each vessel is emphasized because it is important to the analysis of stress and strain and function in morphometry. Experimental results are presented as histories of tissue parameters after step changes of the oxygen level. Tissue characteristics and are examined under the hypothesis that they are linearly related to changes in the local blood pressure. Under this linearity wall hypothesis, each aspect of the tissue change can be expressed as a convolution integral of the blood pressure history with angle a kernel called the indicial response function. It is shown the indicial response function for rising blood pressure is different results from that for falling blood pressure. This difference represents a major nonlinearity of the tissue remodeling process of the blood with vessels.

PURPOSE:Hemorrhage, Endovascular irradiation inhibits neointimal hyperplasia in ballooned and stented arteries but impacts both diseased and adjacent normal tissue. Little is site known about the effects of irradiation on downstream vasculature. In this study, we investigated vascular function and structure of pig treatment coronary arteries distal to sites of endoluminal irradiation. MATERIALS AND METHODS: Vasomotor responses of distal arteries to contraction of KCl to and PGF2alpha and endothelium-dependent (substance P and A23187) and -independent (sodium nitroprusside) relaxation were studied in naïve, sham-treated, irradiated, stented,adherent and stented plus irradiated vessels. Light and scanning electron microscopy were used to assess vascular morphology. RESULTS: Relaxations to substance Relaxations P and A23187 at 1 month post treatment were significantly decreased in the irradiated group, whereas contractile response to PGF2alpha contractility was significantly increased. Hemorrhage, mural thrombus, and inflammation were present at the upstream-irradiated site; inflammatory cells were also present adherent and to the endothelium in the distal segments. CONCLUSIONS: Distal vasomotor function reflects an influence from the nature of a proximal and intervention. The effect of irradiation on downstream conduit arteries to increase the threshold of contractility and suppress endothelium-dependent relaxation may -independent be related to the presence of inflammatory cells at both the upstream-instrumented site as well as the distal location.

Lung had biopsy in cattle for the diagnosis of lung diseases is rarely used or described. The clinical effects and the gross complications findings in lung and pleura after ultrasonic-guided percutaneous lung biopsy in the upright animal of healthy cattle were reported previously h (Braun et al., 1999). This report describes the yield of attained lung tissue and the local tissue reaction in 60 the healthy adult cows slaughtered 24 h (50 animals) and 10 days (10 animals) after invasion. The yield of lung tissue between in the biopsies was high (85.5%) in 90 histologically examined biopsy specimens and judged 'good to excellent'. The local tissue the reaction and the extent of haemorrhage in the lung parenchyma, both 24 h and 10 days after the biopsy, were and minimal. In the latter group, the scar tissue had approximately the same dimensions as the tissue cylinders punched 10 days (10 before. There were no local adhesions between the pleural surfaces. Previously published data concerning clinical reactions and complications, macroscopically examined 10 local tissue bleeding and the histologically evaluated minimal local inflammatory reaction, following lung biopsy of cattle, indicate that this procedure animals) is safe and satisfactory for sampling of accurate lung material. The results of this study concur and indicate that local days complications in the animal were minimal to absent.

The low use of glycosaminoglycans (GAGs) as the second macromolecular component with collagen for the membrane preparation is based on the idea to to create a biodegradable scaffold for new tissue. A hybrid collagen/hyaluronan membrane with specific bubble macrostructure was designed to serve its as a synthetic dermal substitute. The objectives were to explain the two questions: what is the local biological response to the the implanted membrane, and what is its reconstruction rate in tissue. The histological study proved low irritability, good compatibility, ingrowth 7 of autologous tissue starting on day 7 post implantation, and resorption within four weeks. The major part of the implant the was replaced by autologous tissue at the end of three weeks post implantation. The overall local biological response to implant end was very good.