Influence of tumour size on uptake of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model

The relationship between tumour size and uptake of111In-DTPA-labelled pegylated liposomes has been examined in a human head and neck cancer xenograft model in nude mice. The mean tumour uptake of111In-labelled pegylated liposomes at 24 hours was 7.2 ± 6.6% ID/g. Liposome uptake for tumours < 0.1 g, 0.1–1.0 g and > 1.0 g was 15.1 ± 10.8, 5.9 ± 2.2 and 3.0 ± 1.3% ID/g, respectively. An inverse correlation between tumour weight and liposome uptake was observed by both Spearman’s rank correlation test (r s= – 0.573, P< 0.001) and Pearson’s correlation coefficient (r s= – 0.555, P< 0.001). For 18 tumours with macroscopic central necrosis, the ratio of uptake in the tumour rim relative to the necrotic tumour core was 11.2 ± 6.4. Measurement of tumour vascular volume for tumours of various sizes revealed an inverse correlation between tumour weight and tumour vascular volume (Spearman’s rank correlation test, r s= – 0.598, P< 0.001), consistent with poor or heterogeneous vascularization of larger tumours. These data have important implications for the clinical application of pegylated liposome targeted strategies for solid cancers which are discussed in detail. © 2000 Cancer Research Campaig

Mild Idiopathic Infantile Hypercalcemia—Part 1: Biochemical and Genetic Findings

Context: Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. Objective: This work aims to characterize the genetic associations and biochemical profile of mild IIH. Methods: This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. Results: The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. Conclusion: The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants. Keywords: CYP24A1; genetic; hypercalcemia; nephrocalcinosis; nephrolithiasis; vitamin

Cationic polyelectrolytes: A new look at their possible roles as opsonins, as stimulators of respiratory burst in leukocytes, in bacteriolysis, and as modulators of immune-complex diseases (A review hypothesis)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44497/1/10753_2004_Article_BF00915991.pd

Effect of alkalinity source on mechanisms of iron, manganese and zinc removal from acid mine drainage by sulfate-reducing bioreactors

The purpose of this study was to investigate the effect of two different sources of alkalinity source on the mechanisms of metal removal in sulfate-reducing bioreactors. Four upward-flow sulfate-reducing bioreactors each containing a 23 L mixture of organic waste materials and either waste mussel shells or limestone as an alkaline amendment were tested at hydraulic retentions of 3.3 and 10 days to treat acidic mine drainage (pH 2.9, 30 mg/L Fe, 16 mg/L Mn, 5 mg/L Zn) for ten months. A combination of methods was used to examine the effect of alkalinity source on the fate of these metals. Consistent with the monitoring data of the effluent that showed circumneutral pH and low metal concentrations, higher concentrations of Fe, Zn and Mn were found in the spent than the initial substrate, with greater metal and acidity removal in l reactors containing mussel shells (at similar residence times). Sequential extraction procedures found that Fe was mainly in the oxidizable and the residual fractions, Zn in the reducible and residual, and Mn in the exchangeable, reducible and acid extractable fractions. SEM analyses confirmed the presence of pyrite in the substrate, and the use of PHREEQC supported the interpretation that precipitation of iron sulfide and oxyhydroxide minerals, manganese carbonates and zinc sulfide occurred within the substrate for both alkalinity sources. Adsorption edge experiments on the initial substrates confirmed the potential for Zn and Mn to adsorb onto organic materials. Alkalinity source greatly affected system performance with the mussel shell reactors outperforming limestone on a volumetric basis, with the inner surfaces of the mussel shells appearing to be important for greater ongoing alkalinity release, and the outer shells important as metal sorption sites not available in limestone reactors