Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice.

HIV-1 infections are generally initiated at mucosal sites. Thus, IgA antibody, which plays pivotal roles in mucosal immunity, might efficiently prevent HIV infection. However, mounting a highly effective HIV-specific mucosal IgA response by conventional immunization has been challenging and the potency of HIV-specific IgA against infection needs to be addressed in vivo. Here we show that the polymeric IgA form of anti-HIV antibody inhibits HIV mucosal transmission more effectively than the monomeric IgA or IgG1 form in a comparable range of concentrations in humanized mice. To deliver anti-HIV IgA in a continual manner, we devised a hematopoietic stem/progenitor cell (HSPC)-based genetic approach using an IgA gene. We transplanted human HSPCs transduced with a lentiviral construct encoding a class-switched anti-HIV IgA (b12-IgA) into the humanized bone marrow-liver-thymus (BLT) mice. The transgene was expressed specifically in B cells and plasma cells in lymphoid organs and mucosal sites. After vaginal HIV-1 challenge, mucosal CD4(+) T cells in the b12-IgA-producing mice were protected from virus-mediated depletion. Similar results were also obtained in a second humanized model, "human immune system mice." Our study demonstrates the potential of anti-HIV IgA in immunoprophylaxis in vivo, emphasizing the importance of the mucosal IgA response in defense against HIV/AIDS.

Maternal and fetal factors that contribute to the localization of T regulatory cells during pregnancy.

PROBLEM: To determine the interplay between fetal antigenicity and local maternal factors in determining reproductive tract T regulatory (Treg) cell accumulation during pregnancy. METHOD OF STUDY: Examination of maternal Treg composition in the uterus, cervix, and uteroplacental interface (UPI) of murine syngeneic and allogeneic pregnancies and non-pregnant controls by flow cytometry. The impact of fetal antigenicity was defined by either fetal gender in syngeneic pregnancies or by allogeneic paternity. Impact of IL-6 on local Treg composition was determined using syngeneic pregnancies in IL-6(-/-) females. RESULTS: An increased fraction of CD4(+) T cells in the pregnant uterine lymphocytic infiltrate and draining pelvic lymph nodes are Tregs. Maternal IL-6 decreases Treg accumulation within the uterus and to a greater extent in the cervix in syngeneic pregnancy. Fetal antigenicity is matched by accumulation of Tregs to the UPI. Treg accumulation at the UPI of non-antigenic female fetuses is determined by the intrauterine position relative to male siblings. CONCLUSION: Reproductive tract tissue Treg composition during pregnancy is influenced by maternal IL-6 and fetal antigenicity.

Intrathecal lidocaine and sufentanil shorten postoperative recovery after outpatient rectal surgery.

PURPOSE: A short recovery time for same day surgery is important to the patient and the hospital. A prospective, randomized, double-blinded study in the postanesthetic care unit was designed to compare the recovery time from spinal anesthesia with low-dose intrathecal (IT) lidocaine and sufentanil to that with IT lidocaine alone. The incidence of adverse effects was also assessed. METHODS: Forty-nine patients (ASA I-III, age 20-69 yr) underwent spinal anesthesia for rectal surgery. The patients were randomized into two groups. One group (n = 28) received low-dose IT lidocaine (15 mg) and sufentanil (10 microg) and the other group (n = 21) received IT lidocaine (50 mg). The time to ambulation, the incidence of pruritus, and other variables were recorded. Statistical difference was assumed if P < 0.05. RESULTS: Our results show a significantly shorter ambulation time (120 +/- 26 min) after IT low-dose lidocaine (15 mg) and 10 microg sufentanil vs 50 mg IT lidocaine (162 +/- 32 min, P < 0.0001). Patients who received IT lidocaine and sufentanil recovered faster. Fifty percent of the patients who received IT sufentanil suffered from pruritus. CONCLUSION: IT lidocaine (15 mg) and sufentanil resulted in a shorter time to ambulation compared to IT lidocaine (50 mg) alone and provided excellent anesthesia despite its disadvantage of pruritus.

Prophylactic ondansetron does not reduce the incidence of itching induced by intrathecal sufentanil.

PURPOSE: Postoperative itching after intrathecal (IT) narcotics may be a difficult and important problem for both the anesthesiologist and the patient in the postanesthetic care unit. Since some studies have reported success in preventing itching with ondansetron, we designed a prospective, randomized, double-blinded, and controlled study to test whether prophylactic iv ondansetron effectively reduces the incidence of IT sufentanil-induced pruritus. METHODS: Thirty-four patients (ASA I-III, age 18-74 yr) underwent ambulatory surgery after spinal anesthesia with IT lidocaine (15-100 mg) and IT sufentanil (10 microg). The patients were randomized into two groups to receive iv either 4 mL saline (n = 13) or 8 mg ondansetron (n = 21) before the IT injection. The incidence of pruritus and other variables was recorded. Pruritus scores were obtained with a verbal analogue score with 0 meaning none and 10 the worst itching that the patient could imagine. Statistical difference was assumed if P < 0.05. RESULTS: Ondansetron did not reduce the incidence of pruritus (77 vs 81%) compared to placebo (P = 1.000). The pruritus scores (4.4 vs 3.6) of the two groups were not significantly different (P = 0.670). CONCLUSIONS: There are contradictory findings in the literature regarding the effectiveness of ondansetron in preventing narcotic-induced itching. Although some studies have indicated that ondansetron could prevent this side effect of IT narcotics, a recent report suggested that ondansetron is not effective in preventing narcotic-induced itching (sufentanil-morphine) after a Cesarean section. In the present study we obtained similar, negative results.