Electroconvulsive Therapy Effects on Cerebrospinal Fluid Monoamine Metabolites and Platelet Serotonin Uptake In Melancholia

The effects of ECT on 5-hydroxyindoleacetic acid, homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol in cerebrospinal fluid and on kinetic parameters of platelet serotonin uptake were studied in 12 patients with melancholia. There were no significant changes in the monoamine metabolites 3 weeks after initiation of ECT in 12 patients; however, there was a tendency for HVA to increase. The V(max) of serotonin uptake (measured in seven patients) remained unchanged after ECT, but there was a significant increase in K(m), indicating a decreased affinity for serotonin in the carrier.     

Drug discrimination procedures: Differential characteristics of the drug A vs drug B and the drug A vs drug B vs no drug cases

Two groups of pigeons with a history of two choice operant drug discrimination tasks (3.0 mg/kg morphine versus 5.6 mg/kg cocaine, and 3.0 mg/kg morphine versus 3.0 mg/kg cocaine, respectively; Swedberg and Järbe 1985) were subjected to three choice tasks in which responses on a third manipulandum were reinforced in the no drug condition. Training drugs generalization gradients in both groups were similar to those normally obtained in two choice drug versus no drug tasks. The salience differences between the training stimuli within the groups observed in the previous two choice task did not differentially affect the three choice discrimination gradients. Tests with novel drugs after the introduction of the no drug condition yielded increased responding to the no drug condition with the exception of the dopamine agonist apomorphine. Results are discussed in terms of a discrimination learning model specifying principles of relative discriminative stimulus control in various discrimination cases.Portions of these data were presented at the International Union of Pharmacology, IUPHAR, 9th International Congress of Pharmacology Satellite Meeting: European Study Group for Internal Stimulus Control by Electrical Stimulation, Drugs and Other Means, ESISC, London, July 29–August 3, 1984 (Swedberg and Järbe 1984). An earlier version of this work appears in the doctoral thesis by the first author (Swedberg 1985).     

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5′-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month

Summary Eighteen patients with advanced solid cancer were treated with daily 5-dFUrd infusions given over 1 h on days 1–5 of a 4-week cycle. Nine patients received 3 g/m² 5-dFUrd daily and another nine patients 5 g/m². One patient on 5 g/m² 5-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1–2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m² 5-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m² group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5-dEUrd and its metabolites 5-FU and 5-dFUH₂ have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5-dFUrd at the end of the infusion approximated 500 mol/l and 1000 mol/l for the 3 g/m² and 5 g/m² group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2–3 compared with the direct injection of 5-FU.Monthly infusion of 5-dFUrd 5 mg/m² per day on days 1–5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5-dFUrd 3 g/m² per day on days 1–5 were well tolerated.     

Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT-uptake inhibitor,citalopram

The effects in rats of long-term administration of the potent, specific 5-HT uptake inhibitor citalopram have been investigated. Citalopram hydrobromide (MW=405) was given in the diet, 99 or 25 mol/kg daily, for 13 days or orally, 49 mol/kg twice a day, for 14 days. High plasma and brain levels of citalopram were found during the treatment period, whereas negligible amounts were found 24 h after withdrawal. The 5-HT uptake mechanism in blood platelets was completely blocked, since levels of whole blood 5-HT during and shortly (2 days) after treatment were decreased by 75–90%. The drug load after the two highest doses in terms of plasma drug levels was the same as in depressed patients treated with citalopram. Receptor binding technique ex vivo was applied to different brain parts to measure receptor parameters for several neurotransmitters. All data were evaluated by Eadie-Hoffstee analysis. No changes were seen in B _max and K _d for -receptors (³H-dihydroalprenolol) in frontal cortex, occipital+temporal cortex, whole cortex and limbic structures, 5-HT₂ receptors (³H-spiroperidol) in frontal and whole cortex, ₁-receptors (³H-prazosin) in rest of brain and DA D-2 receptors (³H-spiroperidol) in corpus striatum and limbic structures. The uptake mechanism for 5-HT as well as the inhibitory effect of citalopram on this uptake remained unaffected in brain synaptosomes derived from control and from citalopram (99 mol/kg)-treated rats. Thus long-term treatment with citalopram does not induce changes in neurotransmitter receptors as seen with most tricyclic as well as newer atypical antidepressants. Most striking is the lack of - and 5-HT₂ receptor down-regulation. Since citalopram clinically shows clear antidepressant activity, this down-regulation does not seem to be a prerequisite of antidepressant activity.     

Changes in rat dopamine- and serotonin function in vivo after prolonged administration of the specific 5-HT uptake inhibitor,citalopram

The effect of prolonged administration of the potent and specific 5-HT uptake inhibitor citalopram on behavioural measures of dopaminergic and serotonergic activity has been studied in rats. Administration of citalopram in the diet at a daily dose of 99 mol/kg led to supersensitivity to d-amphetamine-induced hypermotility and stereotypy and to subsensitivity to apomorphine-induced hypomotility 2 h after withdrawal. Forepaw clonus induced by 5-methoxy-N,N-dimethyltryptamine was decreased 2 h and 24 h after withdrawal and the number of head shakes induced by 1-5-HTP and citalopram were decreased 24 h after withdrawal. The d-amphetamine potentiation was still seen after 24 h, whereas the response had returned to normal 3 and 7 days after withdrawal. The content of amphetamine in three different brain regions was about 50% higher compared with controls 24 h after withdrawal of prolonged citalopram administration. At this time citalopram had been eliminated, and citalopram itself could not affect amphetamine metabolism. Other experiments indicated a linear relation between d-amphetamine brain concentration and motility level. Thus, a 50% increase in citalopram-treated rats cannot alone account for 3-fold increase in d-amphetamine-induced motility. Potentiation of d-amphetamine-induced hypermotility was also found after citalopram in a daily dietary dose of 25 mol/kg for 13 days and after oral bolus injection (49 mol/kg twice daily for 14 days). Acute citalopram injection had no effect in any of these models. The results suggest increased responsiveness of dopaminergic mechanisms mediating hypermotility, and decreased sensitivity of dopamine receptors mediating sedation (proposed autoreceptors). Sensitivity of 5-HT receptors was also decreased. The mechanisms by which citalopram induces d-amphetamine supersensitivity as well as subsensitivity to apomorphine and 5-HT agonists are presently unknown, since no changes in dopaminergic and serotonergic receptor binding have been found after an identical dose regimen.     

Self-reported health and associated factors among the immigrant populations in Norway

Aim

The immigrant population continues to increase in Norway, and Somali immigrants and their descendants are presently the largest non-Western group. We have limited knowledge about the health status in this population. The aim of this study was to assess self-perceived health status among Somalis in Norway.

Method

We used data from a study assessing risk factors for lifestyle diseases among Somali immigrants in Oslo, which was conducted between December 2015 and October 2016, among men and women aged 20–73 who were living in the Sagene borough in Oslo.

Results

The study population included 221 participants (112 females and 110 males). Overall, 78% of the participants (70% of females and 86% males) rated their health status as good or very good. Women had poorer self-reported health (p?=?0.003) than men. Being unemployed and having diabetes, stress, and sleeping problems were associated with poor self-reported health, but time lived in Norway, education level, Norwegian language proficiency, and high BMI were not significantly associated. Around 2/3 of the participants reported being physically inactive, while around half reported walking or moving more than 30 min per day. Self-reported chronic diseases such as diabetes and hypertension were 5% and 9% respectively.

Conclusion

This study has shown the different patterns of self-reported health status among Somali immigrants in Norway, as associated with gender, age, psychosocial conditions, and employment status. Further research is needed to explain why Somali women in Norway have poorer self-reported health than men. The findings from this study should provide direction to healthcare providers for improving health among immigrants, for example through implementing a community-driven and culturally appropriate lifestyle intervention program.

     

Beyond the Paradigm of Weight Loss in Non-Alcoholic Fatty Liver Disease: From Pathophysiology to Novel Dietary Approaches

Current treatment recommendations for non-alcoholic fatty liver disease (NAFLD) rely heavily on lifestyle interventions. The Mediterranean diet and physical activity, aiming at weight loss, have shown good results in achieving an improvement of this liver disease. However, concerns related to compliance and food accessibility limit the feasibility of this approach, and data on the long-term effects on liver-related outcomes are lacking. Insulin resistance is a central aspect in the pathophysiology of NAFLD; therefore, interventions aiming at the improvement of insulin sensitivity may be preferable. In this literature review, we provide a comprehensive summary of the available evidence on nutritional approaches in the management of NAFLD, involving low-calorie diets, isocaloric diets, and the novel schemes of intermittent fasting. In addition, we explore the harmful role of single nutrients on liver-specific key metabolic pathways, the role of gene susceptibility and microbiota, and behavioral aspects that may impact liver disease and are often underreported in clinical setting. At present, the high variability in terms of study populations and liver-specific outcomes within nutritional studies limits the generalizability of the results and highlights the urgent need of a tailored and standardized approach, as seen in regulatory trials in Non-Alcoholic Steatohepatitis (NASH).     

The Potential of Anti-Bullying Efforts to Prevent Academic Failure and Youth Crime. A Case Using the Olweus Bullying Prevention Program (OBPP)

Prevention Science - The effectiveness of bullying prevention programs has led to expectations that these programs could have effects beyond their primary goals. By reducing the number of victims...     

Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation

Allogeneic islet transplantation in type 1 diabetes requires lifelong immunosuppression to prevent graft rejection. This medication can cause adverse effects and increases the susceptibility for infections and malignancies. Adoptive therapies with regulatory T cells (Tregs) have shown promise in reducing the need for immunosuppression in human transplantation settings but have previously not been evaluated in islet transplantation. In this study, five patients with type 1 diabetes undergoing intraportal allogeneic islet transplantation were co-infused with polyclonal autologous Tregs under a standard immunosuppressive regimen. Patients underwent leaukapheresis from which Tregs were purified by magnetic-activated cell sorting (MACS) and cryopreserved until transplantation. Dose ranges of 0.14–1.27 × 10⁶ T cells per kilo bodyweight were transplanted. No negative effects were seen related to the Treg infusion, regardless of cell dose. Only minor complications related to the immunosuppressive drugs were reported. This first-in-man study of autologous Treg infusion in allogenic pancreatic islet transplantation shows that the treatment is safe and feasible. Based on these results, future efficacy studies will be developed under the label of advanced therapeutic medical products (ATMP), using modified or expanded Tregs with the aim of minimizing the need for chronic immunosuppressive medication in islet transplantation.     

An Orthotopic Liver Transplantation Patient Survived Without Hepatic Artery Flow Due to Thrombosis: A Case Report

BackgroundHepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation, almost always leads to morbidity and mortality without urgent revascularization or retransplantation, especially if HAT occurs within a few days after transplantation.Case PresentationHerein we describe a case report of an orthotopic liver transplantation patient surviving without hepatic artery flow due to HAT on postoperative day 1. Reanastomosis, thrombectomy, and intra-arterial thrombolysis were performed, but only retrograde arterial flow by Doppler ultrasound, not by angiography, could be demonstrated in the hepatic artery. This case report is in compliance with the Declaration of Helsinki and the Declaration of Istanbul.ConclusionBased on the evidence from this patient, we believe that patients with failed revascularization can experience a long-term survival with conservative treatment. Retransplantation should be evaluated based on laboratory findings because graft function in individual patients can recover.