Intracerebroventricular anaerobic dopamine in Parkinson's disease with L-dopa-related complications: a phase 1/2 randomized-controlled trial.

Continuous compensation for cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. Dopamine does not cross the digestive and blood-brain barriers and is rapidly oxidized. The new concept is the intracerebroventricular administration of anaerobic dopamine (A-dopamine) using an abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum.

Ondansetron induced blindness: a pharmacovigilance database study.

Background: Ondansetron is an antiemetic drug (AED) used to prevent and treat nausea and vomiting. The summary of product characteristics reports a rare risk of transient blindness primarily during IV injections, notably with the concomitant use of chemotherapeutic agents. We aimed to refine the characterization of ondansetron-induced blindness.

Fosfomycin-induced agranulocytosis: a case report and review of the literature.

Background: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.

Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.

Design, Setting, And Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium.

Trial of Deferiprone in Parkinson's Disease.

Background: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.

Methods: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa.

Myeloneuropathy induced by recreational nitrous oxide use with variable exposure levels.

Background And Purpose: Although several case series have described nitrous-oxide-associated neurological disorders, a comprehensive assessment of exposure characteristics (e.g., time to onset, level of exposure) in substance abusers has not been performed.

Effects of acute ethanol and/or diazepam exposure on immediate and delayed hippocampal metabolite levels in rats anesthetized with isoflurane.

Alcohol and benzodiazepines are psychoactive substances frequently associated in voluntary drug intoxications that share common mechanisms of action, including facilitation of GABAergic transmission. This study aimed to assess the separate and combined effects of ethanol and diazepam acute exposure on hippocampal metabolite levels, as well as on delayed cognitive performance, in rats anesthetized with isoflurane. Adult male Wistar rats received one intraperitoneal injection containing either saline solution ("CTL" group, N = 15), a 5-mg/kg dose of diazepam ("DIA" group, N = 16), a 2-g/kg dose of ethanol ("EtOH" group, N = 18), or a 5-mg/kg dose of diazepam + a 2-g/kg dose of ethanol ("DIA + EtOH" group, N = 24).

Lack of direct involvement of a diazepam long-term treatment in the occurrence of irreversible cognitive impairment: a pre-clinical approach.

Several observational studies have found a link between the long-term use of benzodiazepines and dementia, which remains controversial. Our study was designed to assess (i) whether the long-term use of benzodiazepines, at two different doses, has an irreversible effect on cognition, (ii) and whether there is an age-dependent effect. One hundred and five C57Bl/6 male mice were randomly assigned to the 15 mg/kg/day, the 30 mg/kg/day diazepam-supplemented pellets, or the control group.

Beneficial effects of atorvastatin on sex-specific cognitive impairment induced by a cerebral microhaemorrhage in mice.

Background And Purposes: Cerebral microhaemorrhages (CMHs) are associated with cognitive decline in humans. In rodents, CMHs induces cognitive impairment in male mice along with sex-specific cortical and hippocampal changes affecting neural, glial and vascular functions. Statins, have been proposed to prevent cognitive decline.

Sex Differences in Cognitive Impairment Induced by Cerebral Microhemorrhage.

It has been suggested that cerebral microhemorrhages (CMHs) could be involved in cognitive decline. However, little is known about the sex-dependency of this effect. Using a multimodal approach combining behavioral tests, in vivo imaging, biochemistry, and molecular biology, we studied the cortical and hippocampal impact of a CMH in male and female mice (C57BL/6J) 6 weeks post-induction using a collagenase-induced model.

Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study.

Background: Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.

Aim: To determine if abiraterone was associated with an increased proportion of AT and HF reports among all suspected adverse drug reactions (ADRs) reported in several pharmacovigilance databases compared with enzalutamide, other ADTs and all other drugs.

Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?

The risk of intracerebral hemorrhage still greatly limits the use of tPA in stroke patients. Research is ongoing in order to identify the pathophysiological mechanisms at play, detect predictive biomarkers and discover new pharmacological targets to develop preventive or curative treatments. Going through experimental and clinical studies, this review focuses on the role of neutrophils as key predictive biomarkers for thrombolysis-induced hemorrhages and as pharmacological targets to limit their occurrence.

Role of cortical microbleeds in cognitive impairment: In vivo behavioral and imaging characterization of a novel murine model.

Cerebral microbleeds (CMBs) could contribute to cognitive impairment in the general population and in patients with dementia. We designed a study to (i) develop a murine model of CMBs, (ii) assess whether CMBs affect cognition in this model and (iii) assess whether this model is sensitive to pharmacological modulation. Male C57Bl6/J mice were stereotactically administered collagenase to induce cortical lesion analysed by MRI at 24 h.

Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke.

Objective: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia.

Methods: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis).

Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia.

Background And Purpose: From the clinical and experimental data available, statins appear to be interesting drug candidates for preventive neuroprotection in ischaemic stroke. However, their acute protective effect is, as yet, unconfirmed.

Experimental Approach: Male C57Bl6/JRj mice were subjected to middle cerebral artery occlusion and treated acutely with atorvastatin (10-20 mg·kg(-1) day(-1) ; 24 or 72 h).

Recovery of brain biomarkers following peroxisome proliferator-activated receptor agonist neuroprotective treatment before ischemic stroke.

Background: Lipid lowering agent such as agonists of peroxisome proliferator-activated receptors (PPAR) are suggested as neuroprotective agents and may protect from the sequelae of brain ischemic stroke. Although the demonstration is not clearly established in human, the underlying molecular mechanism may be of interest for future therapeutic purposes. To this end, we have used our well established rodent model of ischemia-reperfusion pre-treated or not with fenofibrate or atorvastatin and performed a differential proteomics analyses of the brain and analysed the protein markers which levels returned to "normal" following pre-treatments with PPARα agonists.

PPARα is involved in the multitargeted effects of a pretreatment with atorvastatin in experimental stroke.

There is now substantial data in the literature showing that statins can protect against cerebral ischemia. This neuroprotective potency is related to their pleiotropic effects that modulate various pathways implicated in the pathophysiology of stroke. It has been demonstrated that statins exert anti-inflammatory and vasculoprotective effects, thus contributing to a reduction in infarct size.