Experimental allergic encephalomyelitis in cynomolgus monkeys. Quantitation of T cell responses in peripheral blood.

Chronic relapsing-remitting experimental allergic encephalomyelitis (EAE) was induced in cynomolgus monkeys by a single immunization with a homogenate of human brain white matter (BH) in adjuvant. Proliferative T lymphocyte responses to BH, to myelin basic protein (MBP), but not to proteolipid protein, were detected in peripheral blood mononuclear cells (PBMC) of all animals and persisted until their death or, in surviving animals, for greater than 10 mo postimmunization. Responses of higher magnitude tended to be associated with fatal, compared with nonfatal, episodes of clinical EAE. The frequency of MBP-reactive T cells in PBMC of animals with acute EAE was quantitated with a soft agar colony system; the ratio of T cells that proliferated specifically to MBP was estimated at between 5 and 20 per 10(6) PBMC. A similar frequency of peptide-specific T cells was estimated from PBMC of monkeys immunized with a synthetic 14-mer peptide corresponding to a region near the carboxy terminus of MBP. Thus, autoantigen-reactive T cells can be detected in the circulation throughout the course of chronic EAE, are predictive of disease severity, and occur at a frequency similar to that estimated to be present in humans with multiple sclerosis

Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy

Aim To determine the rate of major congenital anomalies in offspring of a large group of women with diabetes mellitus treated with insulin lispro (Humalog®). Methods This multinational, multicentre, retrospective study included mothers with diabetes mellitus (diagnosed prior to conception) who were treated with insulin lispro for at least 1 month before conception and during at least the first trimester of pregnancy. Anomalies were assessed by two independent dysmorphologists not affiliated with the sponsor. Results The charts of 496 women were reviewed for 533 pregnancies resulting in 542 offspring (500 live births, 31 spontaneous and seven elective abortions, and four stillbirths). Mothers’ characteristics: mean ( ± SD ) age was 29.9 ( ± 5.2) years, 85.6% were Caucasian and 97.2% had Type 1 diabetes mellitus. Insulin lispro continued to be the main mealtime insulin for more than 96% of the women during the second and third trimester. The dysmorphologists determined that 27 (5.4%) offspring had major congenital anomalies and 2 (0.4%) offspring had minor congenital anomalies. Conclusions The rate of major congenital anomalies was 5.4% [95% CI (3.45%, 7.44%)] for offspring of mothers with diabetes mellitus treated with insulin lispro before and during pregnancy. The current published rates of major anomalies in infants born to mothers with diabetes treated with insulin are between 2.1 and 10.9%. This suggests that the anomaly rate with insulin lispro treatment does not differ from the published major congenital anomaly rates for other insulin treatments

Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-City Cohort

Rationale: Stress-elicited disruption of immunity begins in utero

The challenges and future considerations regarding pregnancy-related outcomes in women with pre-existing diabetes

Ineffective management of blood glucose levels during preconception and pregnancy has been associated with severe maternal and fetal complications in women with pre-existing diabetes. Studies have demonstrated that preconception counseling and pre-pregnancy care can dramatically reduce these risks. However, pregnancy-related outcomes in women with diabetes continue to be less than ideal. This review highlights and discusses a variety of patient, provider, and organizational factors that can contribute to these suboptimal outcomes. Based on the findings of studies reviewed and authors’ clinical and research experiences, recommendations have been proposed focusing on various aspects of care provided, including improved accessibility to effective preconception and pregnancy-related care and better organized clinic consultations that are sensitive to women’s diabetes and pregnancy needs