Objective
Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We ...evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy.
Methods
Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK‐8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis.
Results
Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines.
Conclusion
Neratinib, as a single agent or in combination with chemo‐irradiation, may be a promising treatment option for patients with head and neck cancer.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
The aim of this systematic review was to give the best available evidence on the impact of professional tooth cleaning (PTC) and scaling and root planing (SRP) on oral halitosis in patients ...with periodontal diseases.
Material and methods
Three databases were screened for relevant studies. Only randomized controlled trials (RCTs) or controlled clinical trials (CCT) were included.
The primary outcome in all included studies was volatile sulphur compounds (VSC) measured by Halimeter or OralChroma and organoleptic scores as secondary outcome.
Only studies investigating healthy adults except for periodontitis or gingivitis were included. The considered intervention strategies were professional tooth cleaning and non‐surgical periodontal treatment. For both strategies, additional oral hygiene instructions (OHI) were possible. Two independent reviewers performed the study selection and quality assessment.
Search results
After and title screening and subsequent full‐text reading of potential papers, a placebo‐controlled RCT could not be found. However, eight studies or particular arms used PTC or SRP as sole interventions and were included in this review.
All trials or study arms included showed a positive effect on VSC levels or organoleptic scores after intervention.
Conclusions
Based on best available evidence, PTC and SRP in combination with oral hygiene instructions reduced VSC values in patients with oral halitosis and/or periodontal diseases, independent of tongue cleaning and the use of mouth rinses.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme ...activity, of AA-selective cytosolic phospholipase A(2)(cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E(2) (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca(2+)-independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
We present evidence that plant growth at elevated atmospheric CO2 increases the high‐temperature tolerance of photosynthesis in a wide variety of plant species under both greenhouse and ...field conditions. We grew plants at ambient CO2 (~ 360 μmol mol−1) and elevated CO2 (550–1000 μmol mol−1) in three separate growth facilities, including the Nevada Desert Free‐Air Carbon Dioxide Enrichment (FACE) facility. Excised leaves from both the ambient and elevated CO2 treatments were exposed to temperatures ranging from 28 to 48 °C. In more than half the species examined (4 of 7, 3 of 5, and 3 of 5 species in the three facilities), leaves from elevated CO2‐grown plants maintained PSII efficiency (Fv/Fm) to significantly higher temperatures than ambient‐grown leaves. This enhanced PSII thermotolerance was found in both woody and herbaceous species and in both monocots and dicots. Detailed experiments conducted with Cucumis sativus showed that the greater Fv/Fm in elevated versus ambient CO2‐grown leaves following heat stress was due to both a higher Fm and a lower Fo, and that Fv/Fm differences between elevated and ambient CO2‐grown leaves persisted for at least 20 h following heat shock. Cucumis sativus leaves from elevated CO2‐grown plants had a critical temperature for the rapid rise in Fo that averaged 2·9 °C higher than leaves from ambient CO2‐grown plants, and maintained a higher maximal rate of net CO2 assimilation following heat shock. Given that photosynthesis is considered to be the physiological process most sensitive to high‐temperature damage and that rising atmospheric CO2 content will drive temperature increases in many already stressful environments, this CO2‐induced increase in plant high‐temperature tolerance may have a substantial impact on both the productivity and distribution of many plant species in the 21st century.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ultrasound (US) facilitates central venous catheter (CVC) placement in children. A new supraclavicular approach using the brachiocephalic vein (BCV) for US-guided CVC placement in very small children ...has been recently described. In 2012, we changed our departmental standard and used the left BCV as preferred puncture site during CVC placement. In our retrospective analysis, we compared US-guided cannulation of the BCV with other puncture sites (control).
We performed a retrospective analysis of all CVC cannulations from October 2012 to October 2013 in our department. For cannulation of the BCV, the in-plane technique was used to guide the needle into the target vein.
We performed CVC cannulations in 106 children (age 1-day to 18 years). In 29 patients, the weight was <4.5 kg. CVC placement was successful in all patients. The left BCV could be used in 81.1% of all cases. In a Poisson regression model of punctures regressed by age, weight or group (left BCV vs. control), age, weight or the cannulation site did not influence the number of punctures. In a logistic regression model of complications (yes vs. no) regressed by the group (left brachiocephalic vs. control) an odds ratio of 0.15 was observed (95% confidence interval 0.03-0.72, P likelihood ratio test = 0.007).
US-guided puncture of the left BCV is a safe method of CVC placement in children. The use of the left BCV was associated with a high success rate in our retrospective analysis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A device was developed allowing to generate simulated human blood pressure signals for the purpose of testing the performance of automated noninvasive sphygmomanometers. The apparatus reproducibly ...generates blood-pressure oscillations synthesized from prerecorded measurements on human subjects. These real-life data allow for a much better evaluation of the accuracy of blood-pressure measurements than the existing simulators using artificial and thus less realistic waveforms. To assess the performance of a given sphygmomanometer under both stable and varying conditions, generated signals can be repeated in their original shape or distorted by well-defined artifacts. In comparison to clinical tests, the procedural influences on the performance testing of sphygmomanometers are largely reduced when the simulator is used.
Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that ...extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To investigate the proposed molecular characteristics of sugar-mediated repression of photosynthetic genes during plant acclimation to elevated CO2, we examined the relationship between the ...accumulation and metabolism of nonstructural carbohydrates and changes in ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) gene expression in leaves of Arabidopsis thaliana exposed to elevated CO2. Long-term growth of Arabidopsis at high CO2 (1000 microliter L-1) resulted in a 2-fold increase in nonstructural carbohydrates, a large decrease in the expression of Rubisco protein and in the transcript of rbcL, the gene encoding the large subunit of Rubisco (approximately 35-40%), and an even greater decline in mRNA of rbcS, the gene encoding the small subunit (approximately 60%). This differential response of protein and mRNAs suggests that transcriptional/posttranscriptional processes and protein turnover may determine the final amount of leaf Rubisco protein at high CO2. Analysis of mRNA levels of individual rbcS genes indicated that reduction in total rbcS transcripts was caused by decreased expression of all four rbcS genes. Short-term transfer of Arabidopsis plants grown at ambient CO2 to high CO2 resulted in a decrease in total rbcS mRNA by d 6, whereas Rubisco content and rbcL mRNA decreased by d 9. Transfer to high CO2 reduced the maximum expression level of the primary rbcS genes (1A and, particularly, 3B) by limiting their normal pattern of accumulation through the night period. The decreased nighttime levels of rbcS mRNA were associated with a nocturnal increase in leaf hexoses. We suggest that prolonged nighttime hexose metabolism resulting from exposure to elevated CO2 affects rbcS transcript accumulation and, ultimately, the level of Rubisco protein
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background Merkel cell carcinoma (MCC) is a rare and aggressive skin malignancy. Late stage MCC treatment options include radio- and chemotherapy. The aim of this study was to assess the expression ...of polo-like-kinase-1 (PLK1) in MCC and whether the PLK1 inhibitor BI2536 is a potential therapeutic option in MCC. Material and methods To evaluate PLK1 expression in patient specimens a tissue microarray was constructed for immunohistochemical staining. The two MCC cell lines MCC13 and MCC26 were exposed to increasing doses of BI2536 in combination with cisplatin or irradiation. Suppression of PLK1 was measured by Western blot analysis. Clonogenic assays were performed after irradiation to evaluate long-term results. Apoptotic and necrotic fractions were measured via flow cytometry. Results BI2536 is capable of inhibiting cell proliferation with an IC50 of 12nM. Combination with cisplatin is synergistic and a partially synergistic effect in combination with irradiation was detected. Clonogenic survival is inhibited synergistically. BI2536 induces apoptosis in MCC cell lines. Conclusion PLK1 seems to be a promising target in the treatment of MCC. Treatment with BI2536, a potent inhibitor of PLK1, resulted in suppression of MCC growth in vitro. Our data warrant further investigations for the potential use of BI2536 in MCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
We evaluated dehydroepiandrosterone sulfate (DHEAS) levels in premature ovarian failure (POF) patients with and without Hashimoto's thyroiditis, and the impact of DHEA supplementation on ...thyroid autoantibodies. In a retrospective case series, we included 67 women with spontaneous POF who received estrogen/gestagen replacement with or without DHEA (30 mg/day) for 3 months. Women who were seropositive for thyroglobulin antibodies and/or thyroperoxidase autoantibodies (n = 30) revealed lower pretherapeutic DHEAS levels (1.2 μg/ml, range 0.4-2.9 μg/ml vs. 1.9 μg/ml, range 0.2-3.9 μg/ml; p < 0.001). DHEAS showed an inverse correlation with both thyroglobulin antibodies (r = −0.426, p < 0.001) and thyroperoxidase autoantibodies (r = −0.362, p = 0.002). When treated with additional DHEA, significant decreases were found for thyroperoxidase autoantibodies (median 85.0 IU/ml, range 41-600 IU/ml vs. median 51.0 IU/ml, range 20-589 IU/ml; p = 0.005) but not for thyroglobulin antibodies.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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