IGF-binding protein-2 protects against the development of obesity and insulin resistance.

Proliferation of adipocyte precursors and their differentiation into mature adipocytes contributes to the development of obesity in mammals. IGF-I is a potent mitogen and important stimulus for adipocyte differentiation. The biological actions of IGFs are closely regulated by a family of IGF-binding proteins (IGFBPs), which exert predominantly inhibitory effects. IGFBP-2 is the principal binding protein secreted by differentiating white preadipocytes, suggesting a potential role in the development of obesity. We have generated transgenic mice overexpressing human IGFBP-2 under the control of its native promoter, and we show that overexpression of IGFBP-2 is associated with reduced susceptibility to obesity and improved insulin sensitivity. Whereas wild-type littermates developed glucose intolerance and increased blood pressure with aging, mice overexpressing IGFBP-2 were protected. Furthermore, when fed a high-fat/high-energy diet, IGFBP-2-overexpressing mice were resistant to the development of obesity and insulin resistance. This lean phenotype was associated with decreased leptin levels, increased glucose sensitivity, and lower blood pressure compared with wild-type animals consuming similar amounts of high-fat diet. Our in vitro data suggest a direct effect of IGFBP-2 preventing adipogenesis as indicated by the ability of recombinant IGFBP-2 to impair 3T3-L1 differentiation. These findings suggest an important, novel role for IGFBP-2 in obesity prevention.

Disruption of learned irrelevance in acute schizophrenia in a novel continuous within-subject paradigm suitable for fMRI.

Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to learn an association between the CS and an unconditioned stimulus (UCS). In LIrr preexposure consists of intermixed presentations of both CS and UCS in a random relationship to each other. In both paradigms preexposure leads in normal subjects to reduced or retarded learning of the CS-UCS association. Acute schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between-groups difference in trials to learning, so posing problems for neuroimaging. We have developed a novel, continuous, within-subject paradigm in which normal subjects show robust and repeated LIrr. We show that this paradigm is suitable for functional magnetic resonance imaging (fMRI) and gives rise, in normal subjects, to activation in the hippocampal formation, consistent with data from animal experiments on LI. We also report, consistent with previous studies of LI, loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate learning, precluding measurement in this group of LIrr. These findings establish the likely value of the new paradigm for neuroimaging studies of attentional dysfunction in acute schizophrenia.

Reproductive and morphological condition of wild mink (Mustela vison) and river otters (Lutra canadensis) in relation to chlorinated hydrocarbon contamination.

We assessed chlorinated hydrocarbon contamination of mink and river otters on the Columbia and Fraser River systems of northwestern North America, in relation to morphological measures of condition. We obtained carcasses of mink and river otters from commercial trappers during the winters 1994-1995 and 1995-1996. Necropsies included evaluation of the following biological parameters: sex, body mass and length, age, thymus, heart, liver, lung, spleen, pancreas, kidney, gonad, omentum, adrenal gland and baculum masses, baculum length, and stomach contents. Livers were analyzed, individually or in pools, for residues of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans. Contaminant levels were relatively low compared to those documented in other North American populations, although they ranged higher than those detected during an earlier survey (1990-1992) of these regional populations. Body condition varied slightly among collection regions, but showed no relationship with contaminant burden. Mink from the upper Fraser River had less fat stores and also had some of the lowest OC contamination levels observed. Similarly, a few individuals with enlarged livers and kidneys had low contaminant levels. Although a few individual animals with gross abnormalities of reproductive systems did not show high levels of contamination, there was a significant negative correlation between total PCB concentrations (as Aroclor 1260) and baculum length in juvenile mink (r = 0.707; p = 0.033; n = 8). The association of juvenile baculum length with eventual reproductive success is unknown, but further characterization of reproductive organ morphology and relationship to contaminants should be undertaken in a larger subset of these populations.

Analbuminaemia. Clinical and laboratory features in a South African patient.

A 10-year-old white boy suffering from primary analbuminaemia presented with a 6-month history of ankle oedema. From infancy he had suffered from asthma and respiratory tract infections. His somatic growth was retarded but his mental and motor development was normal. The plasma albumin level was markedly reduced (81 mg/l) but a number of other plasma protein levels showed compensatory increases above the normal range. A study of the binding of unconjugated bilirubin added to the patient's plasma in vitro revealed an accumulation within the high-density lipoprotein fraction. It is suggested that the relative absence of severe illness in analbuminaemia reflects similar compensatory mechanisms afforded by the increase in non-albumin plasma protein levels and by other metabolic adjustments.

Cardiac dysrhythmia following reversal of neuromuscular blocking agents in geriatric patients.

Ninety-three patients 65 years of age or older were studied to determine the incidence of dysrhymia following administration of 1 of 2 cholinesterase inhibitors, neostigmine or pyridostigmine. The ECG was then continuously monitored for 90 minutes. Neostigmine was associated with a higher incidence of dysrhythmia than was pyridostigmine. Neostigmine administered to patients with pre-existing coronary artery disease and/or conduction defects and to patients with hypertension was associated with a significantly higher incidence of dysrhythmia than was pyridostigmine when administered to patients with the same conditions. The incidence of dysrhythmia in patients who received a halogenated anesthetic was 5 times greater after neostigmine than after pyridostigmine.

Malignant hyperpyrexia.

Malignant hyperpyrexia is a genetically related syndrome that cannot be predicted reliably in advance of administration of anesthesia except by a strong family history. The definitive etiology is unknown, although triggering agents that release calcium from the calcium-storing sarcoplasmic membrane of the muscle cell are highly suspect. As soon as the syndrome is diagnosed, therapy must be prompt, vigorous, and carried out with the same urgency as a cardiac arrest. Specific therapy with dantrolene sodium may prove to be an answer to this serious problem in anesthetic practice.

Awareness, dreams, and hallucinations associated with general anesthesia.

This incidence of mental aberrations (awareness, dreams, and hallucinations) in 490 adult patients undergoing a variety of surgical procedures was investigated. The total incidence of mental aberrations reported was 11 percent (awareness 1 percent, halluncinations 2 percent, dreams 8 percent). No statistically significant correlation was found between the incidence of unusual mental reactions and the anesthetic agents employed, the age or sex of the patients, or the duration or type of surgical prcedure.