Cardiovascular complications and mortality determinants in near drowning victims: A 5-year retrospective analysis

none8noneOmar, Hesham R; Mirsaeidi, Mehdi; Bosco, Gerardo; Morgan, Kevin; Dalvi, Prachiti; Helal, Engy; Mangar, Devanand; Camporesi, Enrico M.Omar, Hesham R; Mirsaeidi, Mehdi; Bosco, Gerardo; Morgan, Kevin; Dalvi, Prachiti; Helal, Engy; Mangar, Devanand; Camporesi, Enrico M

Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients

Hyperbaric oxygen therapy (HBOT) has beneficial effects on avascular necrosis of femoral head (ANFH), but its mechanism of action is still unclear. We investigated if HBOT upregulates serum osteoprotegerin (OPG) and/or inhibits osteoclast activation. 23 patients with unilateral ANFH at stage I, II and III consented to the study: the patients received standard HBOT. Serum OPG levels were obtained at the beginning of HBOT (T0), after 15 sessions (T1), 30 sessions (T2), after a 30-day break (T3), and after 60 sessions (T4). Magnetic resonance imaging (MRI) was obtained at T0 and about one year from the end of HBO treatments. Lesion size was compared between pre- and post-HBOT. 19 patients completed the study. HBOT reduced pain symptoms in all patients. HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III patients. HBOT increased serum OPG levels but receptor activator of nuclear factor kappa-B ligand (RANKL) levels did not change

The Interaction of Escitalopram and R-Citalopram At the Human Serotonin Transporter Investigated in the Mouse

Rationale: Escitalopram appears to be a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, thereby curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and hence antidepressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram\u27s inhibition hereof.Objectives: Primary: Investigate at the human (h)SERT, at clinical relevant doses, whether R-citalopram antagonizes escitalopram-induced 5-HTExt elevation. Secondary: Investigate whether abolishing the putative allosteric site affects escitalopram-induced 5-HTExt elevation and/or modulates the effect of R-citalopram.Methods: Recombinant generation of hSERT transgenic mice; in vivo microdialysis; SERT binding; pharmacokinetics; 5-HT sensitive behaviors (tail suspension, marble burying).Results: We generated mice expressing either the wild-type human SERT (hSERTWT) or hSERT carrying amino acid substitutions (A505V, L506F, I507L, S574T and I575T) collectively abolishing the putative allosteric site (hSERTALI/VFL+SI/TT). One mg/kg escitalopram yielded clinical relevant plasma levels and brain levels consistent with therapeutic SERT occupancy. The hSERT mice showed normal basal 5-HTExt levels. Escitalopram-induced 5-HTExt elevation was not decreased by R-citalopram co-treatment and was unaffected by loss of the allosteric site. The behavioral effects of the clinically relevant escitalopram dose were small and tended to be enhanced by R-citalopram co-administration.Conclusions: We find no evidence that R-citalopram directly antagonizes escitalopram or that the putative allosteric site is important for hSERT inhibition by escitalopram

The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse

RATIONALE: Escitalopram is a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, curtailing the elevation of extracellular 5-hydroxytryptamine (5-HT(Ext)), and antidepressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram’s inhibition hereof. OBJECTIVES: Primary: Investigate at the human (h)SERT, at clinical relevant doses, whether R-citalopram antagonizes escitalopram-induced 5-HT(Ext) elevation. Secondary: Investigate whether abolishing the putative allosteric site affects escitalopram-induced 5-HT(Ext) elevation and/or modulates the effect of R-citalopram. METHODS: Recombinant technology; in vivo microdialysis; receptor binding; pharmacokinetics; 5-HT sensitive behaviors (tail suspension, marble burying). RESULTS: We generated mice expressing either the wild-type human SERT (hSERT(WT)) or hSERT carrying amino acid substitutions (A505V, L506F, I507L, S574T and I575T) collectively abolishing the putative allosteric site (hSERT(ALI/VFL+SI/TT)). One mg/kg escitalopram yielded clinical relevant plasma levels and brain levels consistent with therapeutic SERT occupancy. Importantly, escitalopram-induced 5-HT(Ext) elevation was not decreased by R-citalopram co-treatment. Further, escitalopram-induced 5-HT(Ext) elevation was not affected by loss of the allosteric site. The behavioral effects of the clinically relevant escitalopram dose were small, tending to be enhanced by R-citalopram co-administration. CONCLUSIONS: We find no evidence that R-citalopram directly antagonizes escitalopram or that the putative allosteric site is important for hSERT inhibition by escitalopram. Our findings points to mechanisms for R-citalopram antagonism of escitalopram’s antidepressant action other than direct antagonistic binding interactions at the hSERT