Annie Collins

Acute intermittent porphyria: New morphologic and biochemical findings

Abstract This paper presents the results of postmortem morphologic and biochemical studies on a patient with acute intermittent porphyria (AIP); there was evidence suggesting the syndrome of inappropriate antidiuretic hormone (ADH) release. Examination of the brain revealed injury to the median eminence and bilateral loss of neurones of the supraoptic and paraventricular nuclei. This represents the first correlation of a specific hypothalamic lesion with the syndrome of inappropriate ADH release. The activity of hepatic δ-aminolevulinic acid synthetase (ALA synthetase), a mitochondrial enzyme which normally is rate-limiting for porphyrin biosynthesis, was increased sevenfold above normal. The high level of this enzyme explains the increased porphyrin precursor excretions seen in AIP. Three general mechanisms, including an operator constitutive mutation, have been discussed as possible explanations of the induction of hepatic ALA synthetase.

Risk preference following adolescent alcohol use is associated with corrupted encoding of costs but not rewards by mesolimbic dopamine

Several emerging theories of addiction have described how abused substances exploit vulnerabilities in decision-making processes. These vulnerabilities have been proposed to result from pharmacologically corrupted neural mechanisms of normal brain valuation systems. High alcohol intake in rats during adolescence has been shown to increase risk preference, leading to suboptimal performance on a decision-making task when tested in adulthood. Understanding how alcohol use corrupts decision making in this way has significant clinical implications. However, the underlying mechanism by which alcohol use increases risk preference remains unclear. To address this central issue, we assessed dopamine neurotransmission with fast-scan cyclic voltammetry during reward valuation and risk-based decision making in rats with and without a history of adolescent alcohol intake. We specifically targeted the mesolimbic dopamine system, the site of action for virtually all abused substances. This system, which continuously develops during the adolescent period, is central to both reward processing and risk-based decision making. We report that a history of adolescent alcohol use alters dopamine signaling to risk but not to reward. Thus, a corruption of cost encoding suggests that adolescent alcohol use leads to long-term changes in decision making by altering the valuation of risk.

Coordinate synthesis of heme and apoenzyme in the formation of tryptophan pyrrolase.

Reciprocal control mechanisms between hemoprotein and 8-aminolevulinic acid synthetase take part in coordinate synthesis of the heme and apoenzyme moieties of tryptophan pyrrolase. Stimulation of heme biosynthesis increases tryptophan pyrrolase, whereas enhancement of heme binding by apotryptophan pyrrolase secondarily increases the formation of δ-aminolevulinic acid synthetase, the rate-limiting enzyme in heme formation. Tryptophan-mediated induction of δ-aminolevulinic acid synthetase suggests that heme participates in repression of that enzyme