Cellular uptake and distribution of cobalt complexes of fluorescent ligands

The development of complexes that allow the monitoring of the release and distribution of fluorescent models of anticancer drugs initially bound to cobalt(III) moieties is reported. Strong quenching of fluorescence upon ligation to cobalt(III) was observed for both the carboxylate- and the hydroximate-bound fluorophores as was the partial return of fluorescence following addition of ascorbate and cysteine. The extent of the increase in the fluorescence intensity observed following addition of these potential reductants is indicative of the fluorophore being displaced from the complex by the action of ascorbate or cysteine, by ligand exchange. The cellular distribution of the fluorescence revealed that coordination to cobalt can dramatically alter the subcellular distribution of a bound fluorophore. This work shows that fluorescence can be an effective means of monitoring these agents in cells, and of determining their sites of activation. The results also reveal that the cytotoxicity of such agents correlates with their uptake and distribution patterns and that these are influenced by the types of ligands attached to the complex.     

Prenatal diagnosis/treatment in families at risk for infants with steroid 21-hydroxylase deficiency (congenital adrenal hyperplasia)

The most common enzymatic defect of steroid synthesis is adrenal steroid 21-hydroxylase deficiency. Inhibited formation of cortisol causes increased pituitary release of ACTH, driving the adrenal cortex to overproduce androgens, whose synthesis does not involve the 21-hydroxylase enzyme. This hormonal setting is established in the embryonic period and affects development of genetic females, misdirecting differentiation of the external genitalia toward male type. At birth, the genitalia are visibly ambiguous (enlarged clitoris, fused labia) or in some cases even male in appearance {phallus with urethral opening, rugated scrotal sac), leading to wrong sex assignment. Adrenal steroid 21-hydroxylase deficiency is the most common basis of female pseudohermaphroditism. These females, however, have normal fertility and potential for gestation (gonads are functional and the internal duct-derived structures are well-formed), thus the sex of rearing should always be female. Management is by life-long hormonal (glucocorticoid) replacement, with surgical correction of the genital ambiguity. Prenatal diagnosis of 21-hydroxylase deficiency, first possible by steroid assay of the amniotic fluid, has utilized HLA typing for identification of loci (antigens B and DR) in close linkage with the 21-hydroxylase gene, and now increasingly relies on DNA analysis for linked HLA or C4 genes or for mutant 21-hydroxylase alleles directly by molecular genetic techniques. The most recent clinical advance is a program of combined prenatal diagnosis with karyotyping and suppression of fetal androgen production in genetic females by steroid administration to the mother. This is the first instance of an inborn metabolic error to be prenatally treated.

A series of 85 managed pregnancies is reported on, including accuracy of diagnosis, response of the mother to steroid treatment, and outcome for treated and untreated male and female fetuses (of 77 born by 6/91). Prenatal diagnosis by current techniques is accurate. Normal growth and development patterns postnatally suggest that dexamethasone treatment is safe.     

Sources of fish in the ephemeral western iishana region of the Cuvelai–Etosha Basin in Angola and Namibia

The triangle between the Kavango and Kunene rivers is drained by the Cuvelai, an ephemeral and deltaic drainage system covering more than 100 000 km². In good rainfall years, the area becomes populated by fish communities dominated by five species migrating southward towards the endorheic Etosha Pan, the basin’s terminal sump. When water dries up, fish subsequently die-off and their sudden appearance in rainy years has captivated scientists for decades. The current study was prompted by hitherto untapped indigenous knowledge through narratives of opportunistic fish harvesting of migrating fish at temporary connections between the Kunene River and the Cuvelai- Etosha Basin. A reconnaissance fish survey in 2017 was complemented by digital satellite images and elevation data analyses. Results support the presence of at least three major ephemeral fish migration routes. The dominant fish genera migrating upstream in Kunene tributaries comprise Enteromius, Oreochromis and Clarias, all eurytopic and known to undertake upstream, lateral and downstream migrations on floodplains. Although other notable fish refugia in the Cuvelai–Etosha Basin are yet to be identified, there is a necessity for the protection and management of these migration routes in tandem with studies on the nature and extent of this inter-basin fish migration under climate change and variability.