Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Venous Lake of the Lip Treated With a Sclerosing Agent: Report of Two Cases

BACKGROUND: A venous lake is a venous ectasia that appears mostly on the lower lip and other sun-exposed areas of an older person. Treatment of lip venous lake includes surgical excision, laser therapy, infrared coagulation, and cryotherapy. Although the use of sclerotherapy on varicose veins, leg telangiectasia, hemorrhoids, and hemangiomas is well established, the use of sclerotherapy for lip venous lake has not been reported. OBJECTIVE: We present two cases of lip venous lake treated with intralesional injection of 1% polidocanol. METHOD: Two cases are reported, and literature is reviewed. RESULT: The lesions virtually disappeared, leaving an inconspicuous scar, with two sessions of sclerotherapy. Side effects were not observed. CONCLUSION: Sclerotherapy with polidocanol is effective in the treatment of lip venous lake and offers an alternative to conventional methods.     

Sympathoadrenal excitation and inhibition by lower brainstem stimulation in cats

Effects of stimulation of brainstem sites on hemodynamics and plasma catecholamine levels were assessed in cats under chloralose-urethane anesthesia. Pressor areas of the dorsal medulla (DM) and ventrolateral medulla (VLM) and the depressor area of the paramedian reticular nucleus (PRN) were stimulated electrically using a monopolar electrode, or chemically using sodium glutamate microinjection. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in caval blood above the adrenal veins. Electrical stimulation of the DM and VLM produced increases in blood pressure and in plasma NE and EPI levels that were enhanced after acute vagotomies. The NE and EPI responses were attenuated after acute, bilateral adrenalectomies, confirming augmented adrenomedullary secretion, whereas the pressor responses were intact. Injection of sodium glutamate into the same pressor regions of the DM or VLM also produced pressor responses and elevated plasma catecholamine levels, indicating that the responses resulted from activation of neuronal perikarya. Stimulation of the PRN attenuated pressor and catecholamine responses during stimulation of the DM and VLM. The results indicate that pressor responses during stimulation of the DM and VLM are due at least partly to activation of perikarya in these regions, are associated with but not dependent on adrenomedullary activation, and are enhanced after vagotomy; and that neurons of the PRN exert inhibitory modulation of the pressor and adrenomedullary responses during stimulation of VLM and DM.