A versatile and tunable coating strategy allows control of nanocrystal delivery to cell types in the liver.

There are many liver diseases that could be treated with delivery of therapeutics such as DNA, proteins, or small molecules. Nanoparticles are often proposed as delivery vectors for such therapeutics; however, achieving nanoparticle accumulations in the therapeutically relevant hepatocytes is challenging. In order to address this issue, we have synthesized polymer coated, fluorescent iron oxide nanoparticles that bind and deliver DNA, as well as produce contrast for magnetic resonance imaging (MRI), fluorescence imaging, and transmission electron microscopy (TEM). The composition of the coating can be varied in a facile manner to increase the quantity of poly(ethylene glycol) (PEG) from 0% to 5%, 10%, or 25%, with the aim of reducing opsonization but maintaining DNA binding. We investigated the effect of the nanoparticle coating on DNA binding, cell uptake, cell transfection, and opsonization in vitro. Furthermore, we exploited MRI, fluorescence imaging, and TEM to investigate the distribution of the different formulations in the liver of mice. While MRI and fluorescence imaging showed that each formulation was heavily taken up in the liver at 24 h, the 10% PEG formulation was taken up by the therapeutically relevant hepatocytes more extensively than either the 0% PEG or the 5% PEG, indicating its potential for delivery of therapeutics to the liver.

Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.

Context: Tight glycemic control throughout pregnancy in women with type 1 diabetes is crucial, and knowledge about which factors that affect insulin sensitivity could improve the outcome for both mother and offspring. Objective: To evaluate insulin requirements in women with type 1 diabetes during pregnancy and test whether parity affects insulin requirements. Design: Observational cohort study consisting of women with type 1 diabetes who gave birth at Aarhus University Hospital, Denmark, from 2004 to 2014. Main Outcome Measure: Daily insulin requirement (the hypothesis that parity could affect insulin resistance was formulated before data collection). Results: A total of 380 women with a total of 536 pregnancies were included in the study. Mean age was 31.1 years, and prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1, 40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of 70% (P < 0.0005) at weeks 33 to 36. Overall, insulin requirements increased significantly with parity. The unadjusted differences between P0 and P1, P2, and P3+4 were 9% (P < 0.0005), 12% (P < 0.0005), and 23% (P < 0.0011), respectively. After adjustment for confounders, differences were 13% (P < 0.0005), 20% (P < 0.0005), and 36% (P < 0.0005). We also observed an adjusted difference between P1 and P3+4 of 20% (P < 0.0012). Conclusions: The data show changes in insulin requirements from week to week in pregnancy and indicate that insulin requirements increase with parity. This suggests that the patient's parity probably should be considered in choosing insulin dosages for pregnant women with type 1 diabetes.

Poor pregnancy outcome after octreotide treatment during pregnancy for familial hyperinsulinemic hypoglycemia: a case report.

BACKGROUND: Late familial hyperinsulinemic hypoglycemia is characterized by recurrent episodes of hypoglycemia and an inappropriate insulinemic response. Treatment with octreotide (somatostatin analogue) reduces the prevalence of clinical significant hypoglycemia and might be beneficial during pregnancy. To our knowledge this is the first report of a woman with late familial hyperinsulinemic hypoglycemia experiencing pregnancies with and without octreotide treatment. CASE PRESENTATION: A 35-year-old Caucasian woman known to suffer from late familial hyperinsulinemic hypoglycemia due to a well-known mutation in the insulin receptor gene has been pregnant 6 times. The patient was treated with injections of Sandostatin LAR® (octreotide) during the first four pregnancies. Her first pregnancy in 1999 was unknown until approximately 25th gestational weeks with fatal intrauterine growth retardation. The following two pregnancies were terminated on parental request after a chorion villus biopsy revealed the mutation causing late familial hyperinsulinemic hypoglycemia. During the fourth pregnancy, in which the fetus also had the mutation, serial ultrasound examinations showed a small fetus with appropriate growth. At birth the girl was small for gestational age. She was admitted to the neonatal special care unit due to low blood glucose and intravenous glucose and early feeding was initiated. One day old, her condition deteriorated with signs of an abdominal catastrophe indicating necrotizing enterocolitis. After two laparotomies - both confirming necrotizing enterocolitis - the child died 8 days after birth.In the following two pregnancies Sandostatin LAR® was stopped before pregnancy and the patient was treated only with diet restriction and intensive glucose monitoring. Both pregnancies ended successfully. One child carried the mutation and was small for gestational age at birth while the other child did not carry the mutation and had normal birth weight. CONCLUSION: In a woman with late familial hyperinsulinemic hypoglycemia octreotide was given during the first four pregnancies resulting in 2 cases of early termination of pregnancy on parental request and 2 cases of inappropriate fetal growth and unviable outcome. The following two pregnancies treated with diet only had a successful outcome.