Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙_max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙_max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. Received: 25 July 1996 / Accepted: 14 October 1996     

Nocturnal sleep in huntington's disease

Summary Nocturnal sleep was studied in 16 inpatients with Huntington's disease. In comparison with healthy controls, patients exhibited a disturbed sleep pattern with increased sleep onset latency, reduced sleep efficiency, frequent nocturnal awakenings, more time spent awake and less slow wave sleep. These abnormalities correlated in part with duration of illness, severity of clinical symptoms, and degree of atrophy of the caudate nucleus. Patients showed an increased density of sleep spindles.     

Characteristics of human neural stem cells In Vitro and after transplantation into rat brain

We studied the effect of culturing conditions on the fate of human neural stem cells after transplantation into rat brain. Human neural stem cells cultured in the presence of mitogens without LIF migrated along the ependyma and cerebral vessels of recipients, but to a great extent degenerated by the 20th day after transplantation. Neural stem cells cultured with LIF migrated, apart from the above mentioned pathways, in the cortex and hippocampus, well survived; proliferating cells were retained 30 days after transplantation.__________This revised version was published online in July 2005 with the addition of the issue title and article categoryTranslated from Kletochnye Tekhnologii v Biologii i Meditsine, Vol. 1, No. 1, pp. 13–19, January, 2005     

Negative parenting behaviour as a mediator of the effects of telephone-assisted self-help for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder

A previous randomised controlled trial demonstrated the effects of a telephone-assisted self-help (TASH) intervention for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder (ADHD) on ADHD symptoms, oppositional symptoms, functional impairment, and negative parenting behaviour (per-protocol analyses). In the current study, we examined whether changes in positive and negative parenting behaviour mediated the effects on symptoms and impairment. Parents in an enhancement group (n = 51) participated in a 12-month TASH intervention (eight booklets plus up to 14 telephone consultations) as an adjunct to routine clinical care, whereas parents in a waitlist control group (n = 52) received routine clinical care only. Parents completed measures of child symptoms, child functional impairment, and parenting behaviour at baseline, at 6 months, and at 12 months. The mediating effects of parenting behaviour were examined using regression analyses. Per-protocol analyses (n = 74) revealed a significant indirect intervention effect on functional impairment through negative parenting behaviour at 6 months as well as indirect intervention effects on oppositional symptoms and functional impairment through negative parenting behaviour at 12 months. The indirect effect on ADHD symptoms through negative parenting behaviour at 12 months just failed to reach significance. The analyses yielded no indirect intervention effects through positive parenting behaviour. The study provides some, albeit limited, support for the importance of changes in negative parenting behaviour to achieve changes in symptoms and functional impairment during parent training. In consideration of the inconsistent results of previous studies concerning the mediating role of positive and negative parenting behaviour, further research is required to better understand the mechanisms of change during parent training, also including other possible mediators like parenting stress and parental self-efficacy.

     

Educational and Organizational Interventions to Improve the Usefulness of Clinical Pharmacological Advice for Personalized Drug Dosing Based on Therapeutic Drug Monitoring

This study was aimed at increasing the clinical usefulness of clinical pharmacological advice (CPA) for personalized drug dosing based on therapeutic drug monitoring (TDM). Educational and organizational interventions focused on improving the knowledge of clinical pharmacology among hospital healthcare workers and reducing the incidence of errors throughout the process were planned. After a pre‐interventional period of risk assessment, different list forms of the types of error occurring in the various phases of the process (Phase 1, request for CPA and blood sampling for TDM; Phase 2, sample delivery to and check in at the CPU; Phase 3, TDM execution and CPA production) were created. In the interventional period, the errors were collected daily and educational programmes were carried out. The pre‐intervention error rate was 19.5%, and resulted significantly higher for the requests coming from the medical wards compared with those from the surgical wards or the ICUs (26.0% versus 10.5% versus 13.7%, p < 0.001). The educational programme trained 303 nurses and 145 physicians. Afterwards, the error percentage progressively dropped (15.5% in the 2nd trimester; 12.3% in the 3rd one; 10.5% in the 4th one). The adopted strategy resulted in significant improvements which may be useful both to improve quality of patient care and to reduce waste in healthcare costs.     

Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome

Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia and HELLP syndrome.     

Characteristics of Suture Materials Used in Oral Surgery: Systematic Review

BackgroundThe aim of this review was to evaluate the most used suture materials with regards to their inflammatory response, their bacterial adhesion, and their physical properties when used to close oral wounds.MethodsFour databases (PubMed, Scopus, Dentistry & Oral Sciences, and OVID) were searched to retrieve relevant studies from January 1, 2000, to January 31, 2020.ResultsOut of the 269 articles, only 13 studies were selected as they were relevant and met the systematic review's protocol. These studies showed that almost all suture materials studies (catgut, polyglycolic acid [PGA] sutures, nylon, expanded polytetrafluoroethylene, and silk sutures) caused bacterial adherence and tissue reaction. In nylon and chromic catgut, the number of bacteria accumulated was lowest. Silk and nylon were found to be more impacted than catgut and PGA in terms of physical characteristics such as tensile strength. PGA, on the other hand, was said to be the most susceptible to knot unwinding.ConclusionsFollowing an oral surgical operation, all sutures revealed varied degrees of irritation and microbial accumulation. Nonresorbable monofilament synthetic sutures, however, exhibited less tissue response and less microbial accumulation.     

A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group

RATIONALE: Studies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are available on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. OBJECTIVE: A 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. METHODS: This study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54-89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. RESULTS: Clinical improvement (> or =20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p<0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p<0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p<0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. CONCLUSIONS: Long-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients.