Identification of periodontal pathogens in atherosclerotic vessels

BACKGROUND: Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study was to determine if viable oral bacteria could be isolated from atherosclerotic lesions and if DNA from periodontal pathogens could be detected by use of polymerase chain reaction (PCR) techniques. METHODS: Seventy-nine specimens of atherosclerotic plaque removed from carotid or femoral arteries during surgery were immediately transferred to reduced transport fluid and brought to the laboratory. The calcified tissue was meticulously cut into fine pieces and used for cultivation of Porphyromonas gingivalis, Prevotella intermedia, P. nigrescens, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and oral streptococci. The material from 24 of the specimens was homogenized, DNA was extracted, and PCR amplification of 16S rDNA with universal and specific primers was carried out. Finally, the PCR products were sequenced. RESULTS: None of the samples yielded growth of the oral bacteria under investigation. In all the 24 specimens bacterial DNA was detected and likewise DNA of P. intermedia was found in the samples. P. nigrescens and P. gingivalis were found sporadically. CONCLUSIONS: Viable oral bacteria could not be isolated from the atheromas, but the data confirm that DNA of periodontal pathogens can be detected in atherosclerotic plaques. However, the finding that DNA from P. intermedia constantly occured in the examined samples was new. Further studies may focus on the simultaneous occurrence of identical clones of this species in subgingival plaque and atherosclerotic plaques.     

Periodontal and hematological characteristics associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

BACKGROUND: Periodontitis shares several clinical and pathogenic characteristics with chronic arthritis, and there is some degree of coexistence. The aims of this study were to elucidate whether patients with localized aggressive periodontitis (LAgP), generalized aggressive periodontitis (GAgP), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA) share periodontal and hematological characteristics distinguishing them from individuals free of diseases. METHODS: The study population consisted of white adults (or=4 mm, CAL>or=2 mm, and ABL>or=2 mm compared to controls. The percentage of sites with CAL>or=2 mm significantly correlated with the levels of IgM-RF and IgA-RF. Missing teeth in JIA and RA patients were not lost due to periodontitis. Patients with GAgP showed higher levels of leukocytes, including neutrophils, and CRP compared to controls. In part, JIA and RA patients showed similar results. CONCLUSIONS: Young adults with RA may develop periodontal destruction, and these patients require professional attention. Both differences and similarities in periodontal and hematological variables were seen in individuals with periodontitis, JIA, and RA.     

Anorganic porous bovine-derived bone mineral (Bio-Oss) and ePTFE membrane in the treatment of peri-implantitis in cynomolgus monkeys

The purpose of the present study was to evaluate the effect of anorganic porous bovine-derived bone mineral (Bio-Oss) and expanded polytetrafluoroethylene (ePTFE) membrane in the treatment of peri-implantitis. A total of 64 implants with a titanium plasma-sprayed (TPS) surface was inserted in eight cynomolgus monkeys (Macaca fascicularis). After a 3-month healing period with plaque control, experimental peri-implantitis characterized by a bone loss of 4-6 mm was induced during a period of 9-18 months. Surgical treatment involving Bio-Oss+membrane, Bio-Oss, membrane, or a conventional flap procedure (control) only was carried out. The animals were sacrificed six months after treatment. Evaluation by clinical parameters, radiography including quantitative digital subtraction radiography, histology, and stereology demonstrated healthy peri-implant tissue irrespective of the applied surgical procedure. However, the amount of re-osseointegration and the total amount of bone (Bio-Oss and regenerated bone) were significantly higher in defects treated with membrane-covered Bio-Oss as compared with the other three treatment procedures. A mean bone-to-implant contact of 36% was obtained within defects treated with membrane-covered Bio-Oss. The corresponding values for the three other treatment procedures were 13-23%. The Bio-Oss particles were in general highly integrated within the regenerated bone, but the particles in the occlusal part of the defects were entirely surrounded by connective tissue irrespective of membrane coverage. The present study demonstrates that surgical treatment involving Bio-Oss covered by an ePTFE membrane is a useful treatment modality of experimental peri-implantitis around implants with a TPS surface in cynomolgus monkeys. However, the treatment outcome is not as encouraging as seen with membrane-covered autogenous bone graft particles documented in a study with same experimental design.     

Synthesis and structure-activity relationship studies of 2-(N-substituted)-aminobenzimidazoles as potent negative gating modulators ofsmall conductance Ca2+-activated K+ channels

Small conductance Ca2+-activated K+ channels (SK channels) participate in the control of neuronal excitability, in the shaping of action potential firing patterns, and in the regulation of synaptic transmission.SK channel inhibitors have the potential of becoming new drugs for treatment of various psychiatric and neurological diseases such as depression, cognition impairment, and Parkinson's disease. In the present study we describe the structure-activity relationship (SAR) of a class of 2-(N-substituted)-2-aminobenzimidazoles that constitute a novel class of selective SK channel inhibitors that, in contrast to classical SK inhibitors, do not block the pore of the channel. The pore blocker apamin is not displaced by these compounds in binding studies, and they still inhibit SK channels in which the apamin binding site has been abolished by point mutations. These novel SK inhibitors shift the concentration-response curve for Ca2+ toward higher values and represent the first example of negative gating modulation as a mode-of-action for inhibition of SK channels. The first described compound in this class is NS8593 (14), and the most potent analogue identified in this study is the racemic compound 39 (NS11757), which reversibly inhibits SK3-mediated currents with a K(d) value of 9 nM.     

Trisomy 8 in pediatric acute myeloid leukemia: A NOPHO‐AML study

Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO‐AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0–18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO‐AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non‐trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3‐ITD mutations (58%). The 5‐year event‐free survival for patients with +8 alone was 50% and 5‐year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3‐ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3‐ITD in +8 alone. © 2016 Wiley Periodicals, Inc.     

GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis

Rhabdomyosarcoma (RMS) typically arises from skeletal muscle. Currently, RMS in patients with recurrent and metastatic disease have no successful treatment. The molecular pathogenesis of RMS varies based on cancer sub-types. Some embryonal RMS but not other sub-types are driven by sonic hedgehog (Shh) signaling pathway. However, Shh pathway inhibitors particularly smoothened inhibitors are not highly effective in animals. Here, we show that Shh pathway effectors GLI1 and/or GLI2 are over-expressed in the majority of RMS cells and that GANT-61, a specific GLI1/2 inhibitor dampens the proliferation of both embryonal and alveolar RMS cells-derived xenograft tumors thereby blocking their growth. As compared to vehicle-treated control, about 50% tumor growth inhibition occurs in mice receiving GANT-61 treatment. The proliferation inhibition was associated with slowing of cell cycle progression which was mediated by the reduced expression of cyclins D1/2/3 & E and the concomitant induction of p21. GANT-61 not only reduced expression of GLI1/2 in these RMS but also significantly diminished AKT/mTOR signaling. The therapeutic action of GANT-61 was significantly augmented when combined with chemotherapeutic agents employed for RMS therapy such as temsirolimus or vincristine. Finally, reduced expression of proteins driving epithelial mesenchymal transition (EMT) characterized the residual tumors.     

Aero-medical evacuation with interventional lung assist in lung failure patients

OBJECTIVE: Acute respiratory failure can make long distance transport by air extremely difficult. Despite pressurised cabins, the pressure will fall to about three quarters of one atmosphere, and the oxygen partial pressure will fall proportionally. Interventional lung assist (iLA) is a well documented treatment in the critical care unit, but has not been evaluated scientifically in long range aero-medical evacuation. The present animal study was performed to test the feasibility of treating lung failure with iLA during intercontinental air evacuation in a military setting. METHODS: Eight adult female pigs were cannulated in the right axillary artery and the right jugular vein. An arterio-venous iLA device (Novalung) was connected. The ventilator was adjusted to below half of the needed minute volume before the use of iLA. The animals went through different modalities of transportation in ambulances, helicopters and aircraft. Two of the pigs were tested in a hypobaric chamber, and the remaining two animals underwent a 7.5 h intercontinental transportation from Denmark to Greenland in a Hercules C130J transport airplane. RESULTS: It was possible to maintain physiological PaCO(2) and PaO(2) in normal flight altitudes with iLA. Compared to pump-driven ECMO systems iLA is safer and more efficient. The current study demonstrates the feasibility of iLA during military aero-medical evacuation.