Kir6.2 is required for adaptation to stress

Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.     

Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy

The objective of this study was to assess the efficacy and safety of amitriptyline as a treatment of FM. A comprehensive computerized search in Medline (Pubmed), EMBASE and The Cochrane Library was performed. Randomized controlled trials (RCTs) comparing amitriptyline vs placebo in adult patients suffering from FM were identified, the methodological quality was assessed and the results of the main outcomes were evaluated. Ten RCTs were identified. Large clinical variability and statistical heterogeneity precluded quantitative meta-analysis. Overall, the study quality was moderate to high. Amitriptyline 25 mg/day (six RCTs) demonstrated a therapeutic response compared with placebo in the domains of pain, sleep, fatigue and overall patient and investigator impression. This benefit was generally seen at 6-8 weeks of treatment but no effect was noted at 12 weeks. Amitriptyline 50 mg/day (four RCTs) did not demonstrate a therapeutic effect compared with placebo. Neither dose of amitriptyline had an effect on tender points count. No clear statements on adverse events with amitriptyline can be made due to inconsistencies in data among the studies. A definitive clinical recommendation regarding the efficacy of amitriptyline for FM symptoms cannot be made. There is some evidence to support the short-term efficacy of amitriptyline 25 mg/day in FM. There is no evidence to support the efficacy of amitriptyline at higher doses or for periods >8 weeks. More stringent RCTs with longer follow-up periods are required to determine the long-term efficacy and safety of the amitriptyline and define its role in the multidisciplinary management of FM.     

Periodontal Disease and its Association with Angiographically Verified Coronary Artery Disease

Purpose

The aim of this research was to investigate the association of chronic and aggressive periodontitis with the severity of coronary artery disease which was angiographically verified.

Material and methods

Subjects were selected among the hospitalized patients at the University Hospital Centre Zagreb who had coronary angiography done because of the chest pain. Thorough clinical examination included periodontal indices and clinical and socio-demographic characteristics of participants. Subjects were divided in two test groups, acute coronary syndrome (ACS) and stable coronary artery disease (CAD), and the control group with no significant CAD. Data were analyzed using Kruskal-Wallis and Pearson’s Chi-Square test.

Results

From 106 subjects, 66 (62.3%) were hospitalized for ACS, 22 (20.7%) had stable CAD and only 18 (17.0%) had no significant CAD. Only 26 (24.5%) out of 106 patients were never smokers (p<0.05). Chronic periodontitis was the most common finding with 68.2% in ACS group and 54.5% in stable CAD group, while healthy patients without periodontitis (72.6%) were dominant in the control group (p<0.001). Stable CAD group had the highest mean probing depth (PD) 3.92±1.16, gingival recession (GR) 1.34±0.78, clinical attachment level (CAL) 4.60±1.41 and bleeding on probing (BOP) 45.98±26.19 values, whereas ACS group had mean PD value of 3.77±0.91, GR 1.11±0.66, CAL 4.32±1.08 and BOP 41.30±22.09, and no significant CAD group had mean PD value of 3.27±0.97, GR 0.69±0.37, CAL 3.62±1.04 and BOP 26.39±13.92 (p<0.05).

Conclusion

Periodontitis was shown to be associated with angiographically verified coronary artery disease. Physical inactivity, poor oral hygiene and periodontal inflammation were observed in patients with ACS and stable CAD.Key words: Periodontitis, Periodontal Index, Cardiovascular Diseases, Coronary Artery Disease, Coronary Angiography     

Severe Generalized Periodontitis in a Patient with an Aplastic Anemia: a 5 Year Follow-up Case Report

Aplastic anemia is a hematological disorder characterized by pancytopenia. This case report presents a young patient with untreated periodontitis associated with hematological disorders, and cyclosporine therapy. During 2 consecutive days, periodontal therapy which consisted of nonsurgical therapy supplemented with an antibiotic treatment and antifibrinolytic therapy was performed. Commercial microbiological PCR tests and periodontitis IL-1 polymorphism risk test were performed. Following the periodontal therapy, the inflammation was resolved and the patient''s occlusion was restored by means of removable partial dentures. After the 5 year follow-up, the patient still remained with shallow probing depths although there was inadequate compliance during the maintenance phase. Aplastic anemia increases the risk of onset of severe forms of periodontitis that can be additionally complicated with cyclosporine therapy. In such patients, periodontal therapy must be supplemented with antibiotics.Key Words: Anemia, Aplastic; Pancytopenia; Cyclosporine; Antifibrinolytic Agents; Gingival hyperplasia; Periodontitis     

Identification and functional characterization of imatinib‐sensitive DTD1‐PDGFRB and CCDC88C‐PDGFRB fusion genes in eosinophilia‐associated myeloid/lymphoid neoplasms

Eosinophilia‐associated myeloid neoplasms with rearrangement of chromosome bands 5q31‐33 are frequently associated with PDGFRB fusion genes, which are exquisitely sensitive to treatment with imatinib. In search for novel fusion partners of PDGFRB, we analyzed three cases with translocation t(5;20)(q33;p11), t(5;14)(q33;q32), and t(5;17;14)(q33;q11;q32) by 5′‐rapid amplification of cDNA ends polymerase chain reaction (5′‐RACE‐PCR) and DNA‐based long‐distance inverse PCR (LDI‐PCR) with primers derived from PDGFRB. LDI‐PCR revealed a fusion between CCDC88C exon 25 and PDGFRB exon 11 in the case with t(5;17;14)(q33;q11;q32) while 5′‐RACE‐PCR identified fusions between CCDC88C exon 10 and PDGFRB exon 12 and between DTD1 exon 4 and PDGFRB exon 12 in the cases with t(5;14)(q33;q32) and t(5;20)(q33;p11), respectively. The PDGFRB tyrosine‐kinase domain is predicted to be retained in all three fusion proteins. The partner proteins contained coiled‐coil domains or other domains, which putatively lead to constitutive activation of the PDGFRB fusion protein. In vitro functional analyses confirmed transforming activity and imatinib‐sensitivity of the fusion proteins. All three patients achieved rapid and durable complete hematologic remissions on imatinib. © 2014 Wiley Periodicals, Inc.     

Impact of routine angiographic follow-up after percutaneous coronary intervention with drug-eluting stents in the SPIRIT III randomized trial at three years

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.