VA Palo Alto Healthcare System

About: VA Palo Alto Healthcare System is a healthcare organization based out in Palo Alto, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 2548 authors who have published 4605 publications receiving 209938 citations.

Preliminary evidence that plasma oxytocin levels are elevated in major depression.

Abstract: It is well established that the neuropeptide oxytocin (OT) is involved in regulating social behavior, anxiety, and hypothalamic-pituitary-adrenal (HPA) axis physiology in mammals. Because individuals with major depression often exhibit functional irregularities in these measures, we test in this pilot study whether depressed subjects (n=11) exhibit dysregulated OT biology compared to healthy control subjects (n=19). Subjects were hospitalized overnight and blood samples were collected hourly between 1800 and 0900h. Plasma levels of OT, the closely related neuropeptide argine-vasopressin (AVP), and cortisol were quantified. Results indicated that depressed subjects exhibit increased OT levels compared to healthy control subjects, and this difference is most apparent during the nocturnal peak. No depression-related differences in AVP or cortisol levels were discerned. This depression-related elevation in plasma OT levels is consistent with reports of increased hypothalamic OT-expressing neurons and OT mRNA in depressed patients. This present finding is likewise consistent with the hypothesis that dysregulated OT biology may be a biomarker of the emotional distress and impaired social relationships which characterize major depression. Additional research is required to elucidate the role of OT in the pathophysiology of this psychiatric disorder.

Extracellular Signal-Regulated Kinase–Dependent Stabilization of Hepatic Low-Density Lipoprotein Receptor mRNA by Herbal Medicine Berberine

Abstract: Objective— Our recent studies identified berberine (BBR) as a novel cholesterol-lowering drug that upregulates low-density lipoprotein (LDL) receptor expression through mRNA stabilization. Here, we...

Propofol Dosing Regimens for ICU Sedation Based upon an Integrated Pharmacokinetic– Pharmacodynamic Model

Abstract: BackgroundThe pharmacology of propofol infusions administered for long-term sedation of intensive care unit (ICU) patients has not been fully characterized. The aim of the study was to develop propofol dosing guidelines for ICU sedation based on an integrated pharmacokinetic–pharmacodynamic model of

A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence.

Abstract: Background. The unique pharmacological properties of buprenorphine may make it a useful maintenance therapy for opiate addiction. This meta-analysis considers the effectiveness of buprenorphine relative to methadone. Methods. A systematic literature search identified five randomized clinical trials comparing buprenorphine to methadone. Data from these trials were obtained. Retention in treatment was analyzed with a Cox proportional hazards regression. Urinalyses for opiates were studied with analysis of variance and a common method of handling missing values. A meta-analysis was used to combine these results. Results. Subjects who received 8-12 mg/day buprenorphine had 1.26 times the relative risk of discontinuing treatment (95% confidence interval 1.01-1.57) and 8.3% more positive urinalyses (95% confidence interval 2.7-14%) than subjects receiving 50-80 mg/day methadone. Buprenophrine was more effective than 20-35 mg/day methadone. There was substantial variation in outcomes in the different trials. Conclusions. The variation between trials may be due to differences in dose levels, patient exclusion criteria and provision of psychosocial treatment. The difference in the effectiveness of buprenorphine and methadone may be statistically significant, but the differences are small compared to the wide variance in outcomes achieved in different methadone treatment programs. Further research is needed to determine if buprenorphine treatment is more effective than methadone in particular settings or in particular subgroups of patients.

GWAS of epigenetic aging rates in blood reveals a critical role for TERT

Abstract: DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P < 2.7 × 10-11). Causal modeling indicates TERT-specific and independent effects on LTL and IEAA. Experimental hTERT-expression in primary human fibroblasts engenders a linear increase in DNA methylation age with cell population doubling number. Together, these findings indicate a critical role for hTERT in regulating the epigenetic clock, in addition to its established role of compensating for cell replication-dependent telomere shortening.