Examining the Reversibility of Hypothyroidism and Developmental Changes in HYT/HYT Mice versus BALB/CBYJ Euthyroid Controls

Unless treated, congenital hypothyroidism causes severe mental retardation, stunted physical development, and perceptual and motor disabilities. Thyroid hormone is essential for normal brain development during gestation and infancy. Clinical studies indicate that adults treated for hypothyroidism during infancy can still suffer permanent cognitive impaimlents, as seen with below average IQ scores and spatial learning disabilities. The hytlhyt mouse is a rodent model for genetically induced fetal hypothyroidism which affords a means of investigating the somatic, behavioral, and neuroanatomical aspects of this disorder. The present study purported to characterize the hyt/hyt mouse in terms of its long term somatic, behavioral and cognitive development and then examining the reversibility of hypothyroidism and developmental changes in these mice. Thyroxin supplemented hyt/+ mothers and hytlhyt fathers were mated to yield hytlhyt (hypothyroid) and hyt/+ (euthyroid) offspring. Polymerase chain reaction (PCR) analysis was done on tail clippings taken from the mice to determine their genetic make-up. A +I+ (genetically normal, BalbIcBYJ) comparison group was derived from a strain of standard laboratory mouse. A total of 195 subjects were assessed for physical growth, reflexive development, and spatial learning. The grip strength meter was adapted to the mouse for this study. The results showed that even though the hytlhyt mouse was receiving triodothyronine (T3) supplemented in their water, they were significantly impaired when compared with BalbIcBYJ (euthyroid) controls. The hytlhyt mice had reduced physical size and growth, delayed eye opening and ear raising, and deficient spatial learning. The hytlhyt mouse\u27s utility as a rodent model of congenital hypothyroidism was confirmed by the similarity of these findings to other rodent models. This finding reinforced the assumption of genetic thyroid deficiency in the hytlhyt mouse. The grip strength meter was successfully adapted to mice. The combined use of hytlhyt mouse with the grip strength may offer a tool for future studies that are successful at reversing congenital hypothyroidism in-utero and understanding the biological underpinnings of this disorder

Repeated Measures of Blood and Breath Ammonia in Response to Control, Moderate and High Protein Dose in Healthy Men

Abstract Ammonia physiology is important to numerous disease states including urea cycle disorders and hepatic encephalopathy. However, many unknowns persist regarding the ammonia response to common and potentially significant physiologic influences, such as food. Our aim was to evaluate the dynamic range of ammonia in response to an oral protein challenge in healthy participants. We measured blood and breath ammonia at baseline and every hour for 5.5 hours. Healthy men (N = 22, aged 18 to 24 years) consumed a 60 g protein shake (high dose); a subset of 10 consumed a 30 g protein shake (moderate dose) and 12 consumed an electrolyte drink containing 0 g protein (control). Change in blood ammonia over time varied by dose (p = 0.001). Difference in blood ammonia was significant for control versus high (p = 0.0004) and moderate versus high (p = 0.03). Change in breath ammonia over time varied by dose (p < 0.0001). Difference in breath ammonia was significant for control versus moderate (p = 0.03) and control versus high (p = 0.0003). Changes in blood and breath ammonia were detectable by fast, minimally-invasive (blood) or non-invasive (breath) point-of-care ammonia measurement methods. These pilot data may contribute to understanding normal ammonia metabolism. Novel measurement methods may aid research into genetic and metabolic ammonia disorders