Defining vitamin D status using multi-metabolite mathematical modelling: A pregnancy perspective.

Vitamin D deficiency is linked to adverse pregnancy outcomes such as pre-eclampsia (PET) but remains defined by serum measurement of 25-hydroxyvitamin D3 (25(OH)D3) alone. To identify broader changes in vitamin D metabolism during normal and PET pregnancies we developed a relatively simple but fully parametrised mathematical model of the vitamin D metabolic pathway. The data used for parametrisation were serum vitamin D metabolites analysed for a cross-sectional group of women (n = 88); including normal pregnant women at 1 st (NP1, n = 25) and 3rd trimester (NP3, n = 21) and pregnant women with PET (n = 22), as well as non-pregnant female controls (n = 20). To account for the effects various metabolites have upon each other, data were analysed using an ordinary differential equation model of the vitamin D reaction network. Information obtained from the model was then also applied to serum vitamin D metabolome data (n = 50) obtained from a 2nd trimester pregnancy cohort, of which 25 prospectively developed PET. Statistical analysis of the data alone showed no significant difference between NP3 and PET for serum 25(OH)D3 and 24,25(OH)2D3 concentrations. Conversely, a statistical analysis informed by the reaction network model revealed that a better indicator of PET is the ratios of vitamin D metabolites in late pregnancy. Assessing the potential predicative value, no significant difference between NP3 and PET cases at 15 weeks gestation was found. Mathematical modelling offers a novel strategy for defining the impact of vitamin D metabolism on human health. This is particularly relevant within the context of pregnancy, where major changes in vitamin D metabolism occur across gestation, and dysregulated metabolism is evidenced in women with established PET.

Ultrastructural Effects of a Non-Steroidal Ecdysone Agonist, RH-5992, on the Sixth Instar Larva of the Spruce Budworm, Choristoneura fumiferana.

Force feeding of RH-5992 (Tebufenozide), a non-steroidal ecdysone agonist to newly moulted sixth instar larvae of the spruce budworm, Choristoneura fumiferana, (Lepidoptera: Tortricidae) initiates a precocious, incomplete moult. Within 6h post treatment (pt) the larva stops feeding and remains quiescent. Around 12hpt, the head capsule slips partially revealing an untanned new head capsule that appears wrinkled and poorly formed. By 24hrpt, the head capsule slippage is pronounced and there is a mid-dorsal split of the old cuticle in the thoracic region but there is no ecdysis. The larva remains moribund in this state and ultimately dies of starvation and desiccation. The temporal sequence of the external and internal changes of the integument were studied using both scanning and transmission electron microscopy. Within 3hpt, there is hypertrophy of the Golgi complex indicating synthetic activity and soon after, large, putative ecdysial droplets are seen. Within 24h, a new cuticle that lacks the endocuticular lamellae is formed. The formation of the various cuticular components, the degradation of the old cuticle and changes in the organelles of the epidermal cells of the mesothoracic tergite are described. The difference between the natural moult and the one induced by RH-5992 are explained on the basis of molecular events that take place during the moulting cycle. The persistence of this ecdysone agonist in the tissues permits the expression of all the genes that are up-regulated by the presence of the natural hormone but those that are turned on in the absence of the hormone are not expressed.

Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma.

The effect of trimethoprim/sulfamethoxazole (T/SMX, 30 mg/kg, PO, q 12 h for 6 weeks) on thyroid function was evaluated in 21 dogs with pyoderma and normal baseline serum thyroxine concentrations. The population mean serum thyroxine concentration, but not the population mean serum triiodothyronine concentration, was significantly decreased at the end of treatment. After 6 weeks of treatment, the response in 3 dogs to thyrotropin administration was substantially reduced. Radionuclide thyroid imaging of 2 dogs after T/SMX treatment revealed higher-than-normal thyroid technetium 99m pertechnetate uptake, suggestive of an interference with iodide metabolism. Use of T/SMX may cause hypothyroidism, and inadequate thyroid function may be incorrectly diagnosed in dogs treated with this antimicrobial.

Comparative body compositions of the dog and goat.

The weights of certain organs and tissues of dogs and goats were measured and expressed as percentages of the total body weights. Species differences were observed in the contribution of several organs to the body weight. In the goat, a large percentage of the body weight was due to gastrointestinal contents. When calculations were made with the gastrointestinal contents eliminated from the body weight, many of the originally observed differences disappeared. After exclusion of the weight of gastrointestinal contents, only the values for skin, large intestine, and kidneys were significantly different between species. The possible influence of body composition on drug dosage is discussed.