Biomedical subjects

R Mangieri

Publications and source records attributed to R Mangieri.

3 recordsLinked to original sources

PubMed2005

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.

Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.

Animals↗

PubMed2000

Shared oocyte donation: society's benefits.

OBJECTIVE: To assess the efficacy of oocyte donation when a cohort of oocytes is shared between two phenotypically matched recipients. DESIGN: A retrospective analysis of a program using shared anonymous oocyte donation. SETTING: Academic infertility center. PATIENT(S): Recipient women with partial or complete ovarian failure; oocyte donors who have been properly screened. INTERVENTION(S): Each oocyte donor was phenotypically matched with two potential recipients. The cohort of donated oocytes were divided between these two recipients if eight or more mature oocytes were obtained at retrieval. Recipients underwent hormone replacement therapy consisting of down-regulation with a GnRH agonist, transdermal estradiol, and intramuscular progesterone in a dose determined by a previous preparatory cycle. MAIN OUTCOME MEASURE(S): Pregnancy and delivery rates for all transfers originating from a cohort of oocytes obtained by retrieval of a single donor; pregnancy and delivery rates per recipient; rate of conversion of a shared donation cycle to a single recipient. RESULT(S): A total of 249 donor cycles permitted 241 retrievals. Each recipient received 8.3 +/- 3.5 oocytes per donation. There were 424 fresh ETs and 48 frozen ETs performed. For fresh ETs, clinical pregnancy and ongoing or delivery rates per recipient were 56.8% and 49.7%, respectively. For frozen ETs, these rates were 50% and 39.5%. Implantation rates were 31.8% and 26.1% for fresh and frozen ET, respectively. When analyzed per donor retrieval, clinical pregnancy and ongoing or delivery rates were 109.5% and 95.4%. These high pregnancy rates per donor reflect the numerous fresh and frozen ETs that can result from one donor's retrieval. Conversion of a donation cycle from two recipients to one recipient occurred for 26 of 241 cycles (10.8%). CONCLUSION(S): Shared anonymous oocyte donation provides a very high pregnancy rate per donor retrieval that is not achievable with unshared donation. In addition, there is a diminished risk exposure of donors per total completed recipient transfers. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes.

Adult↗

PubMed1999

Oocyte donation: insights into implantation.

OBJECTIVE: To ascertain whether obstetric, gynecologic, or congenital variables affect implantation efficiency or eventual delivery in donor oocyte recipients. DESIGN: Clinical study. SETTING: Academic tertiary care infertility clinic. PATIENT(S): A total of 370 recipients. INTERVENTION(S): Fresh ET following oocyte donation in a hormone replacement cycle. MAIN OUTCOME MEASURE(S): Regression analyses were performed to detect any statistically significant difference in the pregnancy rate (PR), delivery rate, miscarriage rate, or implantation rate associated with different obstetric, gynecologic, and congenital independent variables while accounting for the age of the recipient in each analysis. RESULT(S): For all recipients, a clinical PR per transfer of 58.9% was achieved, with an implantation rate of 30%. A significant decline in the implantation rate was noted in relation to increasing age of the recipient. A history of tubal disease was associated with a significantly lower implantation rate and a significantly lower ongoing and delivered PR. Asherman's syndrome, despite surgical correction, appeared to negatively affect the ongoing and delivered PR. CONCLUSION(S): With the exceptions of recipient age and a history of tubal disease, all other uterine factors studied did not appear to influence the implantation potential of an embryo resulting from oocyte donation. A history of tubal disease had a distinctly negative effect on implantation efficiency and delivery potential for a given recipient. This finding highlights the need to identify the mechanisms underlying the negative effect of tubal disease so that donor oocyte recipients and all other patients with this cause of infertility can benefit from directed therapy.

Adult↗