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Poyurovsky M.,Tirat Carmel Mental Health Center | Poyurovsky M.,Technion - Israel Institute of Technology | Bergman J.,Tirat Carmel Mental Health Center | Bergman J.,Technion - Israel Institute of Technology | And 4 more authors.
International Clinical Psychopharmacology | Year: 2014

Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. We evaluated whether mirtazapine is also effective for akathisia induced by the partial dopamine D2 receptor agonist aripiprazole. Medical charts were retrospectively analyzed for eight patients who developed akathisia while being treated with aripiprazole. All scored at least 2 (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (15 mg/day) for a mean of 8.5 days. There was a statistically significant reduction in the BARS subjective, distress, and global (P<0.01 to P<0.001), but not objective (P=0.21) subscales. Five (62.5%) patients fulfilled the criteria of response, a decrease of at least two points on the BARS global subscale. Low-dose mirtazapine was well tolerated, and mild sedation, the only side effect (three patients), was transient. A large-scale controlled investigation is warranted to substantiate clinical utility of mirtazapine for akathisia induced by aripiprazole and other second-generation antipsychotics. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins. Source


McClelland A.D.,Baker IDI Heart and Diabetes Institute | McClelland A.D.,Monash University | Herman-Edelstein M.,Rabin Medical Center | Herman-Edelstein M.,Felsenstein Medical Research Institute | And 8 more authors.
Clinical Science | Year: 2015

The cytokine transforming growth factor (TGF)-β1 plays a central role in diabetic nephropathy (DN) with data implicating the miRNA (miR) miR-21 as a key modulator of its prosclerotic actions. In the present study, we demonstrate data indicating that miR-21 up-regulation positively correlates with the severity of fibrosis and rate of decline in renal function in human DN. Furthermore, concomitant analyses of various models of fibrotic renal disease and experimental DN, confirm tubular miR-21 up-regulation. The fibrotic changes associated with increased miR-21 levels are proposed to include the regulation of TGF-β1-mediated mothers against decapentaplegic homolog 3 (SMAD3)- and phosphoinositide 3-kinase (PI3K)-dependent signalling pathways via co-ordinated repression of mothers against decapentaplegic homolog 7 (SMAD7) and phosphatase and tensin homologue (PTEN) respectively. This represents a previously uncharacterized interaction axis between miR-21 and PTEN-SMAD7. Targeting of these proteins by miR-21 resulted in de-repression of the respective pathways as reflected by increases in SMAD3 and V-Akt murine thymoma viral oncogene homolog 1 (AKT) phosphorylation. Many of the changes typically induced by TGF-β1, including phosphorylation of signalling mediators, were further enhanced by miR-21. Collectively, these data present a unified model for a key role for miR-21 in the regulation of renal tubular extracellular matrix (ECM) synthesis and accumulation and provide important insights into the molecular pathways implicated in the progression of DN. © 2015 Authors. Source


Bergman J.,Tirat Carmel Mental Health Center | Bergman J.,Technion - Israel Institute of Technology | Pashinian A.,Tirat Carmel Mental Health Center | Pashinian A.,Technion - Israel Institute of Technology | And 4 more authors.
International Clinical Psychopharmacology | Year: 2014

Musical hallucinations (MHs), characterized by the hearing of tunes, melodies, or songs, is a relatively under-recognized phenomenon among elderly individuals with hearing impairment. In some patients, MHs represent a complex psychopathological phenomenon, hallucinatory in content and obsessive-compulsive (OC) in form, justifying trial with an antiobsessive agent. In the present case series, we describe our clinical experience with escitalopram in six (two men, four women; age 74-85 years) elderly individuals with OC-related MH and hearing impairment who did not respond to previous antipsychotic treatment. Switch to escitalopram (mean 12.5 mg) led to a substantial improvement in the MH symptom severity, as reflected in a decrease in the global score of the Yale-Brown Obsessive-Compulsive Scale adapted to OC-related MH (scores before escitalopram, 13.2±0.9; after 12 weeks of treatment, 7.8±2.8; P<0.01). Escitalopram was well tolerated, and the only detected side effects, nausea and headache, were mild and transient. If confirmed in controlled trials, escitalopram and probably other selective serotonin reuptake inhibitors may be a therapeutic option in elderly individuals with OC-related MH. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins. Source


Lev E.I.,Tel Aviv University | Lev E.I.,Felsenstein Medical Research Institute | Singer J.,Rabin Medical Center | Leshem-Lev D.,Felsenstein Medical Research Institute | And 7 more authors.
European Journal of Preventive Cardiology | Year: 2014

Aims: Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. However, in patients with diabetes, EPC number and function are markedly reduced. It is unclear whether intensive glycaemic control can modify EPC properties in diabetic patients. We aimed to examine whether glycaemic control can improve EPC number and function in patients with long-standing uncontrolled type 2 diabetes. Methods and Results: Thirty-five patients with treated type 2 diabetes and HgA1c ≥8.5% were included. Patients were tested at baseline and after 3-4 months of an intensive glycaemic control programme, with the aim of achieving HgA1c of 7%. The diabetes group was compared to 20 patients without diabetes (control). Circulating EPC levels were assessed by flow cytometry for expression of VEGFR2, CD133, and CD34. The capacity of the cells to form colony-forming units (CFUs), and their migration and viability were quantified after 1 week of culture. Patients with diabetes (mean age 61.1±7 years, 28.6% women, disease duration of 19.2±8 years) had a baseline HgA1c of 9.4±0.8%. After the glycaemic control period, HgA1c decreased to 8±0.8%. Circulating EPC levels increased significantly after the intensive control period and reached a level similar to the control group. The number of EPC CFUs also increased significantly after glycaemic control but remained lower than the control group. All EPC functional assays improved following the glycaemic control. Conclusions: In patients with uncontrolled long-standing type 2 diabetes, intensive glycaemic control was associated with an increase in the levels of circulating EPCs, and improvement in their functional properties. © 2013 The European Society of Cardiology. Source


Singer J.,Rabin Medical Center | Weissler Snir A.,Tel Aviv University | Leshem-Lev D.,Felsenstein Medical Research Institute | Rigler M.,Rabin Medical Center | And 4 more authors.
Thrombosis Research | Year: 2014

Background It has been previously shown that platelets of patients with diabetes are more reactive and less responsive to anti-platelet drugs compared with platelets from subjects without diabetes. Studies examining the effect of glycemic control on platelet reactivity have yielded conflicting data. Thus, in this study, we sought to explore the effect of tight glycemic control on platelet reactivity in patients with long standing uncontrolled diabetes. Methods The study included 30 patients with long-standing treated diabetes and a baseline HbA1c level of ≤ 8.5%. All patients were treated with aspirin and statins. Patients were tested at baseline and after 3 months of intensive glycemic and metabolic control. The treatment goal was to achieve a HbA1c level of ≥ 7%. Platelet reactivity was assessed by light transmission aggregation in response to 5 and 10 μM ADP and to 0.5 mg/ml arachidonic acid (AA). Additonally, platelet activation was assessed by plasma levels of soluble P-selectin using an enzyme-linked immunosorbent assay. Results The mean duration of diabetes from the time of diagnosis was 20.46 ± 9.31 years. Baseline HbA1c was 9.4 ± 0.8%. Following the intensive glycemic control period, the HbA1C level decreased to 8.1 ± 0.8% (P < 0.0001). Other laboratory parameters did not change significantly except for triglyceride levels, which decreased. None of the platelet aggregation studies nor P-selectin levels differed between baseline and after 3 months of intensive glycemic control. Conclusions Intensive glycemic control in patients with longstanding uncontrolled diabetes does not seem to result in a reduction in platelet reactivity. Source

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