Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor.
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Nigrostriatal dopaminergic neurons undergo sprouting around the margins of a striatal wound. The mechanism of this periwound sprouting has been unclear. In this study, we have examined the role played by the macrophage and microglial response that follows striatal injury. Macrophages and activated microglia quickly accumulate after injury and reach their greatest numbers in the first week. Subsequently, the number of both cell types declines rapidly in the first month and thereafter more slowly. Macrophage numbers eventually cease to decline, and a sizable group of these cells remains at the wound site and forms a long-term, highly activated resident population. This population of macrophages expresses increasing amounts of glial cell line-derived neurotrophic factor mRNA with time. Brain-derived neurotrophic factor mRNA is also expressed in and around the wound site. Production of this factor is by both activated microglia and, to a lesser extent, macrophages. The production of these potent dopaminergic neurotrophic factors occurs in a similar spatial distribution to sprouting dopaminergic fibers. Moreover, dopamine transporter-positive dopaminergic neurites can be seen growing toward and embracing hemosiderin-filled wound macrophages. The dopaminergic sprouting that accompanies striatal injury thus appears to result from neurotrophic factor secretion by activated macrophages and microglia at the wound site. (+info)
Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?
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Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups (n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally (n = 12) or intravenously (n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly (P<0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity. (+info)
Matrix valency regulates integrin-mediated lymphoid adhesion via Syk kinase.
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Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM. (+info)
The effects of low-copper diets with or without supplemental molybdenum on specific immune responses of stressed cattle.
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Angus bull calves (n = 42; 7 mo of age; 254 kg initial BW) were used to investigate the effects of dietary Cu and Mo on immune function of stressed cattle. Randomly selected calves (n = 22) were injected with 90 mg of Cu as Cu glycinate 28 d before weaning and castrated at weaning. These calves received 7.5 and 5 mg of supplemental Cu/kg of DM during a 41-d receiving phase and a 196-d growing phase, respectively. The remainder of the steers received no supplemental Cu during the experiment. Copper-supplemented steers had adequate Cu status at weaning, whereas unsupplemented calves were marginally Cu-deficient. Cell-mediated response to intradermal injection of phytohemagglutinin was not affected by dietary treatment during the receiving phase. During the growing phase, half of the steers in each Cu treatment were given 5 mg of supplemental Mo/kg of DM. Copper supplementation increased (P<.05) humoral response to ovalbumin injected on d 133 of the growing phase. On d 168 of the growing phase, calves receiving only supplemental Mo were severely Cu-deficient based on plasma and liver Cu concentrations. The other treatment groups had adequate Cu status. Before feeding on d 168 of the growing phase, half of the steers were loaded onto trailers and transported 2.5 h, and they remained on the trailers an additional 9.5 h. Humoral response to porcine erythrocytes (PRBC) and delayed-type hypersensitivity (DTH) to dinitrochlorobenzene was tested at the end of the stress period. There was a Cu x stress interaction for humoral response to PRBC, with Cu decreasing antibody titers in unstressed calves and increasing titers in stressed steers. Stressed steers had lower (P = .03) ADG during the 28 d following stress. The results of this study indicate that Cu deficiency and 5 mg of supplemental Mo/kg of DM do not dramatically alter the specific immunity of stressed cattle. (+info)
Endothelial implants inhibit intimal hyperplasia after porcine angioplasty.
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The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly. (+info)
Effect of leukocytes on corneal cellular proliferation and wound healing.
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PURPOSE: To establish whether fucoidin, by blocking the adhesion of leukocytes on the limbal vascular endothelium, prevents extravasation of the cells from the blood stream into the limbal stroma and the wounded area after corneal injury. Successful leukocyte blocking enabled investigation of the influence of leukocytes on corneal cellular proliferation after corneal wounding. METHODS: Thirty-two New Zealand White rabbits were used. Photorefractive keratectomy (PRK) and a standardized alkali corneal wound were used as models in two sets of experiments. In half of the injured rabbits fucoidin was used to prevent leukocytes from leaving the local vessels. The efficiency of the blocking technique was evaluated by counting the number of leukocytes in the limbal and wounded corneal areas. Proliferating cell nuclear antigen (PCNA) was used as a marker for proliferative activity. RESULTS: The infiltration of leukocytes into the limbus and the cornea after PRK and alkali injuries can be blocked by fucoidin. The healing rate of corneal epithelium after alkali burn was retarded in the absence of leukocytes. PCNA expression was enhanced in the presence of leukocytes. Fucoidin per se had no influence on corneal cell proliferation and wound healing. CONCLUSIONS: Polymorphonuclear leukocytes (PMNs) can be prevented from entering the cornea in vivo by fucoidin after PRK and after alkali burn. The corneal epithelial healing rate is delayed in the absence of PMNs in vivo, and PCNA expression increases in the presence of leukocytes. (+info)
Patterns of healing of scaphoid fractures. The importance of vascularity.
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We studied 45 patients with 46 fractures of the scaphoid who presented sequentially over a period of 21 months. MRI enabled us to relate the pattern of the fracture to the blood supply of the scaphoid. Serial MRI studies of the four main patterns showed that each followed a constant sequence during healing and failure to progress normally predicted nonunion. (+info)
Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group.
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PURPOSE: The safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery (SEPS) for the treatment of chronic venous insufficiency were established in a preliminary report. The long-term clinical outcome and the late complications after SEPS are as yet undetermined. METHODS: The North American Subfascial Endoscopic Perforator Surgery registry collected information on 148 SEPS procedures that were performed in 17 centers in the United States and Canada between August 1, 1993, and February 15, 1996. The data analysis in this study focused on mid-term outcome in 146 patients. RESULTS: One hundred forty-six patients (79 men and 67 women; mean age, 56 years; range, 27 to 87 years) underwent SEPS. One hundred and one patients (69%) had active ulcers (class 6), and 21 (14%) had healed ulcers (class 5). One hundred and three patients (71%) underwent concomitant venous procedures (stripping, 70; high ligation, 17; varicosity avulsion alone, 16). There were no deaths or pulmonary embolisms. One deep venous thrombosis occurred at 2 months. The follow-up periods averaged 24 months (range, 1 to 53 months). Cumulative ulcer healing at 1 year was 88% (median time to healing, 54 days). Concomitant ablation of superficial reflux and lack of deep venous obstruction predicted ulcer healing (P <.05). Clinical score improved from 8.93 to 3.98 at the last follow-up (P <. 0001). Cumulative ulcer recurrence at 1 year was 16% and at 2 years was 28% (standard error, < 10%). Post-thrombotic limbs had a higher 2-year cumulative recurrence rate (46%) than did those limbs with primary valvular incompetence (20%; P <.05). Twenty-eight of the 122 patients (23%) who had class 5 or class 6 ulcers before surgery had an active ulcer at the last follow-up examination. CONCLUSIONS: The interruption of perforators with ablation of superficial reflux is effective in decreasing the symptoms of chronic venous insufficiency and rapidly healing ulcers. Recurrence or new ulcer development, however, is still significant, particularly in post-thrombotic limbs. The reevaluation of the indications for SEPS is warranted because operations in patients without previous deep vein thrombosis are successful but operations in those patients with deep vein thrombosis are less successful. Operations on patients with deep vein occlusion have poor outcomes. (+info)