Rituximab Therapy for Insulin Allergy in Type-1 Diabetes Mellitus.

Background/Objective: Allergic reactions to insulin have decreased significantly since the introduction of human insulin preparation, but up to 2.4% of insulin-treated patients can still be affected. Rituximab is a monoclonal antibody against the surface antigen CD20 on B lymphocytes, and it is largely used to treat lymphoproliferative and rheumatological conditions. In a very few published case reports, rituximab has been used as an investigational drug to treat severe insulin allergy refractory to conventional therapy. Here, we present an unusual case of a 40-year-old woman with T1DM and severe insulin allergy that was successfully treated with rituximab. Case Report: The patient was diagnosed with T1DM at age 37. Three years later, skin reactions developed at insulin administration sites. These consisted of pruritic and painful erythema and wheals that appeared within 1 to 4 h of insulin administration, followed by induration, subcutaneous nodules, and surrounding lipodystrophy that lasted several days with spontaneous resolution in 1 to 2 weeks. Extensive immunologic evaluation suggested the reaction was related to insulin allergy. Skin biopsy revealed sublobular panniculitis. After failed conventional treatment with antihistamines, glucocorticoid, and various insulins, rituximab infusion as an investigational approach was initiated. This was very successful, leading to prolonged remission of her insulin allergy. Discussion: First-line management of insulin allergy should focus on second-generation antihistamines and switching insulin preparation. In refractory cases, systemic immunotherapy with rituximab can be a viable option. Conclusion: Practitioners should be aware that in patients with insulin allergy who fail conventional treatment, immunotherapy with rituximab can be a viable option.

Imaging and Diagnostic Challenges in a Patient With Refractory Hypoglycemia Caused by Insulinomas Related to Multiple Endocrine Neoplasia Type 1.

Insulinoma is a rare neuroendocrine tumor. It may occur sporadically or as part of the genetic tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Diagnosis is challenging because of the small size of insulin producing tumors that lead to hyperinsulinemia. Advances in imaging modalities may provide more accurate diagnosis of primary tumors, metastasis, and tumor functional status. Advances allow for improved medical and surgical management with new tools for research of neuroendocrine tumors. Surgical excision of the primary tumor is often curative; however, insulinomas in MEN1 syndrome are often multifocal with a high rate of recurrence presenting unique challenges in management. Here, we present the case of a 34-year-old male with recurrent hypoglycemic episodes and hyperparathyroidism diagnosed with multiple pancreatic insulinomas secondary to MEN1. Furthermore, we provide a brief review of the literature and discuss the approach to diagnosis and management in patients with MEN1 syndrome and future areas of investigation.

Preliminary investigation of honey-doped electrospun scaffolds to delay wound closure.

Manuka honey is an ancient remedy to improve wound healing; however, an effective delivery system is needed to facilitate extended release of honey into wounds. We developed an electrospun dermal regeneration template consisting of a poly (ε-caprolactone) (PCL) scaffold embedded with 1%, 5%, 10%, or 20% manuka honey. In vitro studies demonstrated that honey PCL scaffolds were not toxic to macrophages, and they allowed for macrophage infiltration into the scaffolds. Vascular endothelial growth factor (VEGF), a marker of angiogenesis, was released by macrophages cultured with scaffolds and macrophage/scaffold conditioned media promoted endothelial cell tube formation in an angiogenesis assay. In a full thickness murine wound model, the scaffolds prevented rapid wound contraction. In vivo, cells infiltrated the scaffolds by post-wounding day 7, but the honey scaffolds did not affect collagen deposition at that time. In summary, preliminary studies investigating the effect of honey on tissue repair show that scaffolds prevent rapid wound contraction, allow for cell infiltration, and promote angiogenesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2620-2628, 2019.

Absence of Endothelial ERα Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice.

The role of estrogen receptor-α (ERα) signaling in the vasculature of females has been described under different experimental conditions and our group recently reported that lack of endothelial cell (EC) ERα in female mice fed a Western diet (WD) results in amelioration of vascular stiffness. Conversely, the role of ERα in the male vasculature in this setting has not been explored. In conditions of overnutrition and insulin resistance, augmented arterial stiffness, endothelial dysfunction, and arterial remodeling contribute to the development of cardiovascular disease. Here, we used a rodent model of decreased ERα expression in ECs [endothelial cell estrogen receptor-α knockout (EC-ERαKO)] to test the hypothesis that, similar to our findings in females, loss of ERα signaling in the endothelium of insulin-resistant males would result in decreased arterial stiffness. EC-ERαKO male mice and same-sex littermates were fed a WD (high in fructose and fat) for 20 weeks and then assessed for vascular function and stiffness. EC-ERαKO mice were heavier than littermates but exhibited decreased vascular stiffness without differences in endothelial-dependent vasodilatory responses. Mesenteric arteries from EC-ERαKO mice had significantly increased diameters, wall cross-sectional areas, and mean wall thicknesses, indicative of outward hypertrophic remodeling. This remodeling paralleled an increased vessel wall content of collagen and elastin, inhibition of matrix metalloproteinase activation and a decrease of the incremental modulus of elasticity. In addition, internal elastic lamina fenestrae were more abundant in the EC-ERαKO mice. In conclusion, loss of endothelial ERα reduces vascular stiffness in male mice fed a WD with an associated outward hypertrophic remodeling of resistance arteries.