Recent clinical trials with stem cells to slow or reverse normal aging processes.

Aging is associated with a decline in the regenerative potential of stem cells. In recent years, several clinical trials have been launched in order to evaluate the efficacy of mesenchymal stem cell interventions to slow or reverse normal aging processes (aging conditions). Information concerning those clinical trials was extracted from national and international databases (United States, EU, China, Japan, and World Health Organization).

Fifty years of experience with loxapine for the rapid non-coercive tranquilization of acute behavioral disturbances in schizophrenia patients, and beyond.

Introduction: Acute behavioral disturbances in psychosis, including agitation, comprise a heterogeneous group of manifestations varying in intensity and duration they last for. They require rapid, non-coercive treatments ranging from verbal de-escalation to the calming effect of pharmacological agents. The treatment goals are reduction of patient suffering and prevention of disease deterioration.

Dosing antipsychotics in special populations of patients with schizophrenia: severe psychotic agitation, first psychotic episode and elderly patients.

Antipsychotic (AP) dosing is well established in nonelderly patients with acute exacerbations of schizophrenia, but not in special populations.This review describes the AP dosing procedures that have been used in clinical studies for acute psychotic agitation, a first episode of psychosis (FEP), and elderly patients. AP dosing data was extracted from the databases of drug regulatory authorities, and from clinical studies available in the medical literature.

Investigational drugs and nutrients for human longevity. Recent clinical trials registered in ClinicalTrials.gov and clinicaltrialsregister.eu.

:Several pharmacological drugs have shown proof of concept for longevity in animal models. I aimed to identify and review those longevity drug candidates that are undergoing clinical trials.:Recent (post-2017) longevity clinical trials were found in US and EU clinical trial registries.

Pharmacotherapeutic approaches to treating depression during the perimenopause.

: Although postnatal depression is now well recognized, there is also a risk of depressive symptoms during perimenopause. The mechanisms underlying perimenopausal depression are still poorly understood; however, there are available treatment options. : This review describes: the current pharmacotherapeutic approaches for perimenopausal depression, their strengths and weakness, and provides recommendations on how current treatment can be improved in the future.

Investigational drugs in recent clinical trials for treatment-resistant depression.

The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies.

AVP-786 for the treatment of agitation in dementia of the Alzheimer's type.

Agitation is common and distressing in patients with Alzheimer-type dementia, but safe, effective treatments remain elusive. Psychological treatments are first-line options, but they have limited efficacy. Off-label psychotropic medications are frequently used, but they also have limited effectiveness, and their use may have harmful side effects, including death.

Investigational drugs for treating agitation in persons with dementia.

Introduction: Agitation is common and distressing in persons with dementia, but safe, effective treatments remain elusive. In this review, the authors describe investigational compounds in ongoing or recently completed clinical trials for this indication and provide an opinion on how they may meet current therapeutic needs.

Areas Covered: Phase II and phase III clinical trials for agitation in persons with dementia were searched in US and EU clinical trial registries and in the medical literature for the period January 2013-February 2016 EXPERT OPINION: The authors searches identified 24 recent clinical trials investigating new treatments for agitation in persons with dementia.

Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries.

Introduction: In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future.

Areas Covered: Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds.

Schizophrenia-spectrum patients treated with long-acting injectable risperidone in real-life clinical settings: functional recovery in remitted versus stable, non-remitted patients (the EVeREST prospective observational cohort study).

Background: Previous studies showed functional improvement in stable patients with schizophrenia treated with risperidone long-acting injection (LAI). We therefore re-investigated functional improvement with risperidone LAI in remitted patients, in comparison with stable patients. The study was conducted in real-life conditions because of the high heterogeneity of the patients' situations.

Potential serotonergic agents for the treatment of schizophrenia.

Introduction: For the last 30 years, drugs targeting serotonin receptors (5-HTR) have been intensively investigated in schizophrenia. New drugs targeting 5-HTRs are under development in patients with schizophrenia.

Areas Covered: In this review, the authors describe the recent clinical trials for schizophrenia with selective serotonergic agents and provide an opinion on how the investigated drugs can help to fulfil current treatment needs.

Bipolar disorder: recent clinical trials and emerging therapies for depressive episodes and maintenance treatment.

Bipolar disorder (BD) is one of the world's ten most disabling conditions. More options are urgently needed for treating bipolar depressive episodes and for safer, more tolerable long-term maintenance treatment. We reviewed 30 recent clinical trials in depressive episodes (eight tested compounds) and 14 clinical trials in maintenance treatment (ten tested compounds).

Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents.

In contrast to the accepted general assumption that polyethylene glycol (PEG) is non-immunogenic and non-antigenic, animal studies clearly showed that uricase, ovalbumin and some other PEGylated agents can elicit antibody formation against PEG (anti-PEG). In humans, anti-PEG may limit therapeutic efficacy and/or reduce tolerance of PEG-asparaginase (PEG-ASNase) in patients with acute lymphoblastic leukemia and of pegloticase in patients with chronic gout, but did not impair hyposensitization of allergic patients with mPEG-modified ragweed extract or honeybee venom or the response to PEG-IFN in patients with hepatitis C. Of major importance is the recent finding of a 22 - 25% occurrence of anti-PEG in healthy blood donors, compared with a very low 0.

Therapeutic perspectives on uricases for gout.

Available recombinant uricases (rasburicase, pegloticase) are potent hypouricaemic agents for tophaceous gout, but their long-term use is in question. We have performed a literature review on uricases, using Scirus, PubMed, Science Direct, and several other search engines. We have also consulted the records of drug regulatory authorities and patents on uricases.

[Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): results obtained in France].

Aim: Information about the variation in the risk for venous thromboembolism (VTE) and in prophylaxis practices in France and around the world is scarce.

Methods: The Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study is a multinational cross-sectional survey designed to assess the prevalence of VTE risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive effective prophylaxis, in accordance with the 2004 American College of Chest Physicians (ACCP) guidelines. This paper gives the results of the ENDORSE study in the French centres in comparison with the global worldwide results of the ENDORSE study and with other Western Europe countries.

Impact of an educational program on the management of bipolar disorder in primary care.

Objective: Government agencies and industry have recently undertaken educational programs for the management of bipolar disorder in primary care, but their medical impact is not well known. Therefore, we conducted a survey among general practitioners to evaluate the impact of the Bipolact Educational Program on the diagnosis and treatment of bipolar disorder.

Methods: A total of 45 general practitioners attending the Bipolact Educational Program (trained group) were compared with a control group of 50 untrained general practitioners on their ability to: (i) diagnose bipolar I and II disorders and (ii) treat bipolar disorder patients appropriately.

Protein kinase A signalling is involved in the relaxant responses to the selective β-oestrogen receptor agonist diarylpropionitrile in rat aortic smooth muscle in vitro.

Objectives: The oestrogen receptor β (ERβ) selective agonist diarylpropionitrile (DPN) relaxes endothelium-denuded rat aorta, but the signalling mechanism is unknown. The aim of this study was to assess whether protein kinase A (PKA) signalling is involved in DPN action.

Methods: cAMP was measured by radioimmunoassay, HSP20 phosphorylation by 2D gel electrophoresis with immunoblotting, and membrane potential and free cytosolic calcium by flow cytometry.

Screening for bipolar disorder in patients consulting general practitioners in France.

Background: Recently, an unexpected 3-fold higher screen positive rate for bipolar disorder was found among low-income American patients who were seeking primary care at an urban general medicine clinic as compared with the general population of the United States. The social health system in France is characterized by its open access, where most bipolar patients ask for care and where the major problem is diagnosis by the general practitioner (GP). Therefore, we investigated the prevalence of bipolar disorder among patients attending GP offices in France.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs).

Endothelium-independent vasorelaxation by the selective alpha estrogen receptor agonist propyl pyrazole triol in rat aortic smooth muscle.

Objectives: This study investigated the signalling mechanism of the relaxant responses to the estrogen receptor (ERalpha) agonist PPT (propyl pyrazole triol) in endothelium-denuded rat aortic rings.

Methods: Several compounds, including protein kinase G (PKG) inhibitors and potassium channel inhibitors, were tested against PPT-dependent rat aortic relaxation. Cyclic GMP and cytosolic calcium responses to PPT in isolated aortic smooth muscle were investigated in parallel.

Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs.

Monodesmethyl cyamemazine and cyamemazine sulfoxide, the two main metabolites of the antipsychotic and anxiolytic phenothiazine cyamemazine, were investigated for their effects on the human ether-à-go-go related gene (hERG) channel expressed in HEK 293 cells and on native I(Na), I(Ca), I(to), I(sus) or I(K1) of human atrial myocytes. Additionally, cyamemazine metabolites were compared with terfenadine for their effects on the QT interval in anaesthetized guinea pigs. Monodesmethyl cyamemazine and cyamemazine sulfoxide reduced hERG current amplitude, with IC50 values of 0.

[Management of comorbid bipolar disorder and alcohol dependence].

Recent studies confirm the clear association between bipolar disorders and alcohol abuse and dependence. Lifetime prevalence of disorders associated with alcohol abuse or dependence appears to be 3 to 4 times higher in patients with bipolar disorders than in the general population. Lifetime prevalence of mood disorders in alcohol-dependent subjects is approximately 10 times higher than in the general population.

Two-year study of relapse prevention by a new education program in schizophrenic patients treated with the same antipsychotic drug.

It is not clear whether patient's psycho-education enhances compliance to antipsychotic treatments and reduces the number of relapses. Here we investigated the impact of a new psycho-educational program (SOLEDUC) on the one- and two-years rate of relapse (primary outcome measure) and a number of clinical assessments (secondary outcome measures). This was a multicentric French clinical trial (51 centers) of Phase IV, open, controlled, randomized, consisting in two parallel groups: the Soleduc group (N=111) and the control group (N=109).