Polioencephalomalacia Secondary to Hypernatremia in Squirrel Monkeys (Saimiri Sciureus).

Polioencephalomalacia Secondary to Hypernatremia in Squirrel Monkeys (Saimiri sciureus).

Vet Pathol. 2013 Jul 30;
Macri SM, Crowell AM, Fenn MS, Knight HL, Westmoreland SV, Miller AD

Squirrel monkeys (Saimiri spp) are one of the most consistently used New World primates in biomedical research and are increasingly being used in neuroscience research, including models of drug abuse and addiction. Spontaneous neurologic disease in the squirrel monkey is uncommonly reported but includes various infectious diseases as well as cerebral amyloidosis. Hypernatremia is an extremely serious condition of hyperosmolarity that occurs as a result of water loss, adipsia, or excess sodium intake. Neurologic effects of hypernatremia reflect the cellular dehydration produced by the shift of water from the intracellular fluid space into the hypertonic extracellular fluid space. Severe hypernatremia may result in cerebrocortical laminar necrosis (polioencephalomalacia) in human patients as well as in a number of domestic species, including pigs, poultry, and ruminants. We report the clinical, histopathologic, and immunohistochemical findings of polioencephalomalacia in 13 squirrel monkeys. Polioencephalomalacia in these animals was associated with hypernatremia that was confirmed by serum levels of sodium greater than 180 mmol/L (reference range, 134.0-154.0 mmol/L [mEq/L]). All animals had concurrent diseases or experimental manipulation that predisposed to adipsia. Immunohistochemical investigation using antibodies to neuronal nuclei (NeuN), CNPase, Iba-1, and CD31 revealed necrosis of predominantly cerebral cortical layers 3, 4, and 5 characterized by neuronal degeneration and loss, oligodendrocytic loss, microglial proliferation, and vascular reactivity. The squirrel monkey is exquisitely sensitive to hyperosmolar metabolic disruption and it is associated with laminar cortical necrosis. HubMed – addiction

Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy.

Clin Infect Dis. 2013 Jul 29;
Vallecillo G, Mojal S, Roquer A, Martinez D, Rossi P, Fonseca F, Muga R, Torrens M

Background.?Concern regarding the QTc interval in HIV-infected patients has been growing in recent years, and cases of prolonged QTc interval and Torsades de Pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Methods.?A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities and changes in their antiretroviral therapy or methadone doses in the last two months were excluded. Heart rate and QT interval in lead II were measured using Bazett’s formula. Results.?Ninety-one patients were included: 58 (63.7%) were males with a median age of 44.5 years and 68/91 (74.7%) were on antiretroviral therapy. Median methadone dose was 70 (15-250) mg/day and mean QTc interval 438+34 ms. Prolonged QTc interval (>450 ms) was documented in 33/91(36.3%) patients and 3/91 (3.2%) had QTc >500 ms. On multiple linear regression analysis methadone doses (P 0.005), chronic hepatitis C-induced cirrhosis (P 0.008) and antiretroviral naive therapy (P 0.036) were predictive of prolonged QTc. Conclusions.?The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses and antiretroviral-naive therapy. Thus, ECG monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group. HubMed – addiction

Estimated Dopamine D2 Receptor Occupancy and Remission in Schizophrenia: Analysis of the CATIE Data.

J Clin Psychopharmacol. 2013 Jul 29;
Moriguchi S, Bies RR, Remington G, Suzuki T, Mamo DC, Watanabe K, Mimura M, Pollock BG, Uchida H

In treating schizophrenia, 65% to 80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D2 receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D2 prediction model. Estimated mean ± SD peak and trough D2 receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D2 occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D2 receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D2 receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia. HubMed – addiction

Diversity of human clock genotypes and consequences.

Prog Mol Biol Transl Sci. 2013; 119: 51-81
Zhang L, Ptá?ek LJ, Fu YH

The molecular clock consists of a number of genes that form transcriptional and posttranscriptional feedback loops, which function together to generate circadian oscillations that give rise to circadian rhythms of our behavioral and physiological processes. Genetic variations in these clock genes have been shown to be associated with phenotypic effects in a repertoire of biological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. Consistently, rodent models carrying mutations in clock genes also demonstrate similar phenotypes. Taken together, these studies suggest that human clock-gene variants contribute to the phenotypic differences observed in various behavioral and physiological processes, although to validate this requires further characterization of the molecular consequences of these polymorphisms. Investigating the diversity of human genotypes and the phenotypic effects of these genetic variations shall advance our understanding of the function of the circadian clock and how we can employ the clock to improve our overall health. HubMed – addiction