Immunosuppression in Uterus Transplantation: Experience From the Dallas Uterus Transplant Study.

BACKGROUND: Uterus transplantation is a temporary transplant allowing women with absolute uterine factor infertility to experience pregnancy and childbirth. The degree of immunosuppression (IS) required to prevent rejection while minimizing toxicity to the recipient and fetus remains an area of investigation. METHODS: In this article, we describe immunosuppressive therapy, rejection episodes, infections, and adverse events in 14 uterus transplant recipients. Induction consisted of antithymocyte globulin and methylprednisolone. Ten recipients (71%) received no steroids postoperatively, and 4 (29%) had steroids tapered off at 42 d. All received oral tacrolimus, either immediate release (n = 2, 14%) or extended release (n = 12, 86%). Mycophenolate was used in 4 cases (29%), de novo azathioprine in 9 (64%), and de novo everolimus in 1 (7%). RESULTS: Sixteen clinically silent, treatment-responsive rejection episodes occurred in 10 recipients. Five recipients (36%) experienced acute kidney injury. In 3 recipients, IS was discontinued due to renal dysfunction. Eleven infection episodes were noted in 7 recipients. No babies had congenital abnormalities. CONCLUSIONS: Our experience demonstrates that safe IS regimens can be used for uterus transplant recipients before and during pregnancy.

The Role of Feral Swine in Human Aortic Infection With Brucella Species.

Brucellosis is one of the most common zoonotic infections in the world. Human infections are the result of direct exposure to infected animals or ingestion of unprocessed dairy products. While Brucella sp. infection has largely been eliminated from commercial cattle and swine with aggressive vaccination, there is a significant prevalence of Brucella sp. infection in the expanding population of feral swine in the US. We report the surgical treatment of a ruptured mycotic aneurysm of the abdominal aorta due to Brucella suis in a woman living in a rural community with a large population of feral swine. Vascular surgeons should be aware that brucellosis can result in arterial infection and should be considered in the differential diagnosis in patients with a history of exposure to feral swine or the ingestion of unprocessed dairy products.

Role of conserved cysteines in the alphavirus E3 protein.

Alphavirus particles are covered by 80 glycoprotein spikes that are essential for viral entry. Spikes consist of the E2 receptor binding protein and the E1 fusion protein. Spike assembly occurs in the endoplasmic reticulum, where E1 associates with pE2, a precursor containing E3 and E2 proteins. E3 is a small, cysteine-rich, extracellular glycoprotein that mediates proper folding of pE2 and its subsequent association with E1. In addition, cleavage of E3 from the assembled spike is required to make the virus particles efficiently fusion competent. We have found that the E3 protein in Sindbis virus contains one disulfide bond between residues Cys19 and Cys25. Replacing either of these two critical cysteines resulted in mutants with attenuated titers. Replacing both cysteines with either alanine or serine resulted in double mutants that were lethal. Insertion of additional cysteines based on E3 proteins from other alphaviruses resulted in either sequential or nested disulfide bond patterns. E3 sequences that formed sequential disulfides yielded virus with near-wild-type titers, while those that contained nested disulfide bonds had attenuated activity. Our data indicate that the role of the cysteine residues in E3 is not primarily structural. We hypothesize that E3 has an enzymatic or functional role in virus assembly, and these possibilities are further discussed.

Maternal cardiac messenger RNA expression of extracellular matrix proteins in mice during pregnancy and the postpartum period.

IMPACT STATEMENT: This study provides the first comprehensive analysis of extracellular matrix protein (ECM) gene expression combined with echocardiographic analyses of heart functional parameters in the murine heart during pregnancy and the early postpartum period. Our findings show regulation of all Timp, selected Mmps, and Col1a1, Col3a1, and Col8a1 mRNA levels with reproductive status, with the greatest number of significant changes occurring in the early postpartum period. Left ventricle cardiac diastolic parameters were the first to change during pregnancy and remained elevated postpartum, whereas systolic parameters were increased in late pregnancy and began to recover during the first week postpartum. These novel findings indicate that although some ECM genes are elevated during late pregnancy, that the postpartum period is a time of robust altered ECM gene expression. These studies provide a basis for examining ECM proteins and their activities in the normal pregnant and postpartum heart and in models of postpartum cardiomyopathy.

Bioactivity of anacardic acid against colorado potato beetle (Leptinotarsa decemlineata) larvae.

Anacardic acid (2-hydroxy-6-alkylbenzoic acid) produced and secreted from glandular trichomes of zonal geranium (Pelargonium x hortorum; Geraniaceae family) provides resistance to small pests (aphids and spider mites). To assess the potential bioactivity of anacardic acid against larger insect pests and to determine if an alternate mode of application (ingestion rather than the topical application) could impart resistance to pests, the effects of anacardic acid consumption on the development of Colorado potato beetle larvae were tested. Analysis of dose-response curves indicated a significant effect on weight gain and mortality. Assessment of food preference (treated versus untreated) indicated larvae avoid food containing anacardic acid and have a lower feeding rate on food containing anacardic acid. On the basis of these results, it is suggested that anacardic acid, applied as a chemical spray or through bioengineering production in crop plants, may provide a new tool in the arsenal to minimize damage to plants caused by pests.