The European Network of the Teratology Information Services (ENTIS) has collected and evaluated data on 689 pregnancies in which exposure to tricyclic and nontricyclic antidepressants occurred. Data ...were collected prospectively from the time of in utero exposure and all the cases were followed up to the first few weeks of postnatal life using standardized procedures. In most cases, no longer term follow-up data were available. Approximately two-thirds of the mothers were on multidrug therapy, and of those, half took a benzodiazepine. About 95% of the patients were exposed during the first trimester. The most striking feature of the pregnancy outcomes is that 97% of live-born babies were morphologically normal. The incidence of spontaneous abortion and late fetal/neonatal deaths were within the normal range. Fourteen live-born babies and one fetus had either major or minor malformations, and six had minor anomalies. However, there was no increase in either a particular type of malformation or a specific pattern of defects. Another 31 infants without malformations had neonatal problems; these were usually associated with chronic multidrug therapy, especially near term. Elective termination of pregnancy occurred more frequently in the multidrug groups (86 out of 488) than in the monotherapy groups (20 out of 201), but data concerning the condition of the fetus are not available in the majority of the cases. Overall, no causal relationship could be established between in utero exposure to antidepressants and adverse pregnancy outcome.
Aims. In France, maintenance programmes for opiate users were adopted later than in other countries. Two maintenance treatments are available: methadone is only delivered in specialized centres while ...high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres. The aim of this study was to compare the socio‐demographic profiles, the practices and drug consumption patterns of the two groups attending specialized centres.
Methodology. The Oppidum Programme (observation of illegal drugs and misuse of psychotropic medications), a multi‐centric survey, surveys drug‐dependent subjects attending specialized care centres throughout France annually. Data were collected by questionnaire on socio‐demographic variables and drug use during the preceding week.
Results. During October 1998, 46 centres took part in the survey. The methadone group (
n = 424) was older, with a better economic situation; 16% used cocaine regularly. The HD buprenorphine group (
n = 616) consumed more heroin (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit acquisitions or irregular consumption. These practices were more frequent for patients consuming the drug "outwith protocol" or for patients obtaining the drug from a general practitioner.
Conclusion. Our results suggest that patterns of consumption of methadone and buprenorphine are different in several respects: concomitant use of licit or illicit psychoactive substances, route of administration, and illegal acquisition. They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices.
Tetrabamate (Atriums), widely used in the treatment of tremor and ethanol-withdrawal symptoms, has been incriminated as a potential cause of reversible acute hepatitis.
We report here on 11 patients ...who experienced tetrabamate-related liver injury, in order to evaluate their clinical, histopathological and evolutive features.
Between 1987 and 1998, 34 cases of tetrabamate-associated acute hepatitis were spontaneously reported to the regional pharmacovigilance center of Lyon. Eleven cases were considered probably to be drug-induced.
There were three males and eight females aged 31-82 years (mean, 57 years). The duration of treatment ranged from 33 to 206 days, and indication for treatment was depressive disorders, tremor or prevention of alcohol withdrawal symptoms. Clinical symptoms were asthenia (n = 9), jaundice (n = 3) and/or diffuse rash (n = 3). The pattern of liver injury was cytolytic (n = 10) or cholestatic (n = 1). Three patients presented biological features of hepatic failure. A percutaneous liver biopsy was performed in six patients. Histological examination of the liver specimen showed a large spectrum of lesions: massive hepatocellular necrosis (n = 1), centrilobular and nonconfluent hepatocyte necrosis (n = 2), intracellular cholestasis (n = 3), and granulomatous hepatitis (n = 1). Tetrabamate was discontinued in all patients. In seven patients, a complete recovery was observed 3 weeks to 3 months after drug withdrawal. Two patients, despite a rapid improvement of liver function tests, died from unrelated causes. The remaining two patients died from irreversible hepatic failure.
Our data strongly suggest that tetrabamate may induce acute liver injury, which may eventually result in life-threatening liver failure.
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•Synthesis and characterization of new NHC-Pt complexes with a TPP+ group.•Our lead compound killed efficiently glioblastoma cancer stem cells.•The addition of triphenylphosphonium ...onto NHC-Pt increases the production of ROS.•The TPP+–NHC-Pt complexes induce an atypical cell death on cancer stem cells.
A growing body of experimental and clinical evidence suggests that rare cell populations, known as cancer stem cells (CSCs), play an important role in the development and therapeutic resistance of several cancers, including glioblastoma. Elimination of these cells is therefore of paramount importance. Interestingly, recent results have shown that the use of drugs that specifically disrupt mitochondria or induce mitochondria-dependent apoptosis can efficiently kill cancer stem cells. In this context, a novel series of platinum(II) complexes bearing N-heterocyclic carbene (NHC) of the type (NHC)PtI2(L) modified with the mitochondria targeting group triphenylphosphonium were synthesized. After a complete characterization of the platinum complexes, the cytotoxicity against two different cancer cell lines, including a cancer stem cell line, was investigated. The best compound reduced the cell viability of both cell lines by 50% in the low μM range, with an approximately 300-fold higher anticancer activity on the CSC line compared to oxaliplatin. Finally, mechanistic studies showed that the triphenylphosphonium functionalized platinum complexes significantly altered mitochondrial function and also induced atypical cell death.
Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, ...having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC's sensitivity to such compounds is thus described.
Nesting hydroxide: Coordination and aerobic oxidation of a bisoxazoline Me2box is coupled with self‐assembly to form a highly ordered (Me2box)O4Zn44+ complex. The metallamacrocycle acts as a ...nest‐like hydroxide receptor (see scheme, right) and shows catalytic phosphatase activity.
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