T cell epitope immunotherapy ameliorates allergic responses in a murine model of shrimp allergy.

BACKGROUND: Shellfish allergy is one of the most common food hypersensitivities worldwide but allergen-specific immunotherapy for shellfish allergy is not yet available. We believe that T cell peptide-based immunotherapy holds the potential for modulating allergic responses without IgE cross-linking. OBJECTIVE: We sought to identify the immunodominant T cell epitopes of tropomyosin, the major shrimp allergen of Metapenaeus ensis (Met e 1), and to evaluate their therapeutic effects in a Balb/c mouse model of Met e 1 hypersensitivity. METHODS: T cell epitopes of Met e 1 were first identified based on the proliferation and cytokine responses of splenocytes isolated from Met e 1-sensitized Balb/c mice upon stimulation by 18 synthetic peptides that span the full-length Met e 1. The immunodominant T cell peptides identified were then fed orally to Met e 1-sensitized Balb/c mice twice a week for four weeks. Allergic responses, serological antibody levels, intestinal histology and systemic and local cytokine profiles were compared between the treated and the untreated groups. RESULTS: Six major Met e 1 T cell epitopes were identified. Mice treated with the T cell epitope peptide mixture demonstrated an amelioration of systemic allergic symptoms and a significant reduction in Th2-associated antibody and cytokine responses. These benefits were accompanied by a shift to a balanced Th1/Th2 response, induction of IgG2a antibodies possessing in vitro and in vivo blocking activities and the induction of regulatory T cell responses. CONCLUSIONS AND CLINICAL RELEVANCE: T cell epitope-based oral immunotherapy is effective in reducing allergic responses towards shrimp tropomyosin. This is a novel strategy for clinical management of shellfish allergy and is a model for mechanistic studies of oral immunotherapy.

Effect of periurethral denervation on function of the female urethra.

OBJECTIVE: The purpose of this study was to determine the effect of periurethral denervation on contractile function of the female rat urethra. STUDY DESIGN: Periurethral nerve transection or sham operation was performed in 16 young female rats. After 2 weeks, contractile function of the external urethra sphincter (EUS) and longitudinal smooth muscle was determined. Inhibitors of nitric oxide (NO) signaling were used to evaluate the role of nitric oxide in nerve-mediated relaxation. Statistical comparisons were conducted by Student t test. RESULTS: Periurethral nerve transection resulted in gross evidence of urinary retention and bladder distention. In normal and sham-operated rats, nerve-mediated relaxation of urethral smooth muscle was inhibited by L-nitroarginine and oxadiazolo quinoxalin-1-one (ODQ), and this relaxation response was impaired significantly after periurethral nerve injury. Relaxation responses to the NO donor sodium nitroprusside remained intact. Contractile function of the EUS was not altered by periurethral nerve injury. CONCLUSION: Neurons surrounding the urethra contain NO and innervate smooth muscle of the inner urethra. Periurethral denervation results in impaired urethral smooth muscle relaxation with no appreciable effect on contractility of the external striated sphincter.

Septate uterus with double cervix and longitudinal vaginal septum. A case report.

BACKGROUND: Congenital uterine anomalies in the general population are estimated to have an incidence of 0.001-10%. The septate uterus, the most common form of structural uterine anomaly, has the highest reproductive failure rate. A rare developmental variant is a septate uterus with cervical duplication and a complete longitudinal vaginal septum. The existence of this anomaly challenges classical müllerian developmental theory. Traditional transabdominal metroplasty has been replaced by operative hysteroscopy in the surgical correction of a septate uterus, with laparoscopy aiding in the diagnosis and contributing to the safety and efficiency of the procedure. CASE: A 28-year-old, nulliparous woman with a septate uterus with cervical duplication and complete longitudinal vaginal septum was diagnosed by combined laparoscopy and hysteroscopy. Excision of the complete longitudinal vaginal septum followed by hysteroscopic partial resection of a thick uterine septum with laparoscopic assistance was performed. However, because of the septum's broad base and the rigidity of the operative resectoscope, we opted to proceed with transabdominal metroplasty. CONCLUSION: Only six cases of septate uterus with cervical duplication and complete longitudinal vaginal septum have been reported. Although its counterpart, the septate uterus, has effects on preterm labor, fetal presentation, infertility and spontaneous abortion, its reproductive outcome has not been assessed. Review of the literature suggests that surgical correction in the setting of poor reproductive outcome has been beneficial. Laparoscopically assisted hysteroscopic resection of the uterine septum is a safe, effective surgical technique of uterine reunification and is preferable to transabdominal methods. However, in certain cases, conventional transabdominal metroplasty may still be required.