Micro- and macro-viscosity relations in high concentration antibody solutions.

Molecular crowding in highly concentrated monoclonal antibody (mAb) solutions results in significant increases in viscosity, which complicates fill-finish steps and patient administration by subcutaneous injection. As viscosity measurements for optimization of the mAb formulation require significant amounts of material not always available in early development, fluorescence correlation spectroscopy (FCS) is evaluated as a potential ultra-low volume technique for viscosity measurement of high concentration protein solutions assuming the Generalised Stokes Einstein relation (GSE) remains valid. Using like-charge fluorescent tracers of different sizes, FCS provided measurements of microviscosities which were compared to the macroviscosity. After parametrising the protein concentration dependence of the viscosity by the exponential coefficient (k) of a simple exponential model, FCS derived k-values of like-size tracer to the crowder followed the same ordering as the macroviscosity derived k-values with respect to solvent conditions. Furthermore, k and the diffusion-derived protein-protein interaction parameter, kD, are linked, and, attractive conditions for mAbs result in a stronger concentration dependence of the viscosity. For tracers and crowders of like-size, a key result is negative deviations from the GSE relation are observed in presence of strong attractive interactions between crowder molecules. These data demonstrate that FCS has application to the screening of high concentration mAb solutions for formulation selection.

Urinary iodine excretion in pregnant women as an index of the impact of a national iodization programme.

OBJECTIVE: To evaluate the extent to which increase in iodine requirement was achieved in pregnant women who attended the antenatal clinic at Harare Central Hospital. DESIGN: Cross sectional. SETTING: Samples were collected from pregnant women attending antenatal clinic at Harare Central Hospital, and from lactating mothers and their infants. SUBJECTS: 100 pregnant women attending the antenatal clinic at Harare Central hospital, 80 infants, 80 lactating women and 18 non-pregnant women. MAIN OUTCOME MEASURES: Comparison of urinary iodine excretion levels among pregnant women, lactating mothers and their infants. RESULT: The results indicated lower urinary iodine excretion levels for the pregnant women and lactating mothers compared to the urinary iodine excretion of the infants and the breast milk iodine content. The urinary iodine excretion level of the non-pregnant control women was median (first and third quartiles): 18.5 microg/dl (30.0, 30.2 microg/dl). The urinary iodine excretion level of the lactating mothers was median (first and third quartiles): 12.0 mg/dl (7.6, 19.5 mg/dl) compared to the level of the infants, median (first and third quartiles): 26.5 mg/dl (18.8, 11.5 mg/dl). A significant difference was noted between the median urinary iodine excretion levels of the mothers, and the median levels of the infants, p = 0.001. The mean milk iodine content was 21.2 +/- 6.8 mg/dl. There was no correlation between breast milk iodine levels and the urinary iodine excretion levels of the infants, (p = 0.96, r = 0.006). Positive correlation was found between maternal urinary iodine excretion levels and the urinary iodine excretion levels of the infants, p = 0.016 r = 0.285. Serum FT4, and TSH levels were found to be higher for infants at six weeks after birth, (FT4 =20.91 +/- 5.65 pmol/L) and median TSH = 2.28 mIU/ml (1.36, 0.86) mIU/rnl, compared to levels at 12 weeks postpartum: (FT4 = 17.53-*6.4 pmol/L) and median TSH = 2.02 mIU/ml, (0.84, 1.55) mIU/ml. The differences were not significant. CONCLUSION: The results indicated a significant reduction in the urinary iodine content of pregnant women, and lactating mothers which did not appear to have any relationship to the urinary iodine excretion levels of infants and iodine content of breast milk. Iodine intake needed to be raised to reflect the recent proposed recommendations.