Effect of cold plasma on periodontal wound healing-an in vitro study.

OBJECTIVES: Cold atmospheric plasma (CAP), a room temperate ionized gas, seems to be a possible way to enhance tissue recovery. An in vitro study was conducted to investigate the influence of medical CAP on the regenerative capacity of human periodontal ligament (PDL) cells. MATERIAL AND METHODS: Human PDL cells were subjected to CAP at various intensities, distances, and durations. The effects of CAP on a number of specific markers were studied at transcriptional level using real-time PCR. Additionally, an in vitro wound healing assay was applied to PDL cell monolayers either in the presence or absence of CAP by using JuLI™ Br Live Cell Analyzer and software. Finally, cell viability of CAP-treated cells was analyzed by an XTT assay. RESULTS: CAP treatment enhanced significantly the expression of the cytokines tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interleukin (IL)-1ß, IL-6, IL-8, collagen (COL)1α, and matrix metalloproteinase (MMP)1, as well as the proliferation markers Ki67 and proliferating cell nuclear antigen (PCNA), but downregulated apoptotic markers Apaf1 and p53. Additionally, the in vitro wound healing rate was significantly enhanced after CAP application. Moreover, CAP treatment resulted in a significantly increased cell viability in the XTT assay. CONCLUSION: This in vitro study shows that CAP has regulatable effects on markers of periodontal wound healing thereby underlining the potential use of CAP as a benefit treatment strategy. CLINICAL RELEVANCE: Our study demonstrates the application of CAP in the treatment of oral pathologies suggesting a promising future treatment approach.

[Is supplemental ear acupuncture for surgical tooth removal with local anesthesia effective? : A pilot study]. / Ist die Supplementierung der Ohrakupunktur bei operativer Zahnentfernung in Lokalanästhesie effektiv? : Eine Pilotstudie.

BACKGROUND: The application of ear acupuncture can contribute to a reduction of acute pain. Data on the application of ear acupuncture following oral surgery in odontology is insufficient. OBJECTIVE: This study investigated the effectiveness of ear acupuncture as an auxiliary analgesic treatment in addition to local anesthesia for operative tooth removal. METHODS: In this prospective open non-randomized pilot study (in accordance with the CONSORT publication) 2 cohorts of 50 patients each with the indications for an operative tooth removal either with or without the application of ear acupuncture in addition to local anesthesia with articain were observed. Patients were allocated to the groups according to their preference. Pain intensity while resting and while chewing was recorded as the primary parameter for a period of 10 days. The secondary parameters were the subjective experience of anxiety and symptoms, such as headaches, dizziness and nausea. RESULTS: The two groups did not differ significantly with respect to demographic variables or the use of local anesthetics. At the various measurement intervals, pain intensity while resting or chewing differed significantly between the two groups (ANOVA, p = 0.004, p = 0.007, respectively). Furthermore, the experience of anxiety (ANOVA, p = 0.0001), the number of patients taking analgesics (χ2-test, p = 0.017) and the total postoperative consumption of analgesics (t-test, 0.001) revealed significant differences. In both groups the numerical rating scales (NRS) for postoperative headaches, dizziness and nausea were low. DISCUSSION AND CONCLUSION: Despite a potential bias and methodological limitations of the study design, the results of this investigation suggest that ear acupuncture influences the experience of pain and anxiety in the postoperative period after tooth removal. As a treatment method with low adverse effects ear acupuncture can contribute to postoperative pain control, especially in patients with preoperative anxiety.

[Pilot study of laser-doppler flowmetry measurement of oral mucosa blood flow].

OBJECTIVE: To explore and compare the perfusion pattern of oral mucosa on Han Chinese and Caucasian by laser-doppler flowmetry. METHODS: A cross-sectional study was carried out, in 20 healthy Han Chinese adult subjects (average age: 28.4 years) and 20 healthy Caucasian (average age: 25.3 years) adult subjects, either gender with 10 subjects. Gingival perfusion was evaluated at 8 points (including upper incisor labial gingival, lower incisor labial gingival, palatal mucosa, cheek mucosa) using a laser-doppler flowmetry(O2C, Medizintechnik GmbH, Germany). Each measurement was carried out 25 seconds consisting 5 seconds of fore period and 20 seconds of work period, without pressure. The measurements were taken by two well- trained doctors, each measurement was exammed 3 times by an examiner, and the average value was recorded as final data. Each measurement has 4 parame ters: SpO2(oxygen saturation), rHB (relative amount of hemoglobin), flow (the blood flow of unit interval), and velocity (blood flow velocity). We compared the data by different sites, different genders, and different races. RESULTS: For palatal gingival, the average SpO2 was 77.1%±10.9%, the average rHB 67.8±11.1, and the average flow 194.1±63.7, which presented significant lower values than other oral mucosa. There was no significant difference among other sites. There was some significant difference between the Caucasian and the Han Chinese: the maxillary central incisor oxygen saturation (SpO2) which were averages of 75.6%±8.2% and 70.4%±7.6%; buccal mucosa hemoglobin (rHB) averages of 79.9±5.8 and 83.5±6.6, which had statistical differences. For most measurement points, the oxygen saturation on men was lower than that on women, which had significant difference. CONCLUSION: To investigate microcirculation pattern, oral mucosa can be the good observation site. Laser-doppler flowmetry is a well-documented instrument to survey on microcirculation.There may be differences between the genders in hemoglobin oxygen-binding capacity, which may have some impact on the ability of soft tissue healing. Oral mucosa display more blood perfusion than attached gingival. As the recipient site of gingival graft, maxilla and mandible have slight difference in blood supply.

[Participation in Preventive Medical Examinations for Children in Saxony-Anhalt (Germany) at the Time of School Entry Medical Examination]. / Inanspruchnahme von Früherkennungsunter-suchungen bei Kindern aus Sachsen-Anhalt zum Zeitpunkt der Schuleingangsuntersuchung.

OBJECTIVE: The aim of this study is to present data concerning children's participation in the German preventive medical examinations for children ("U2" to "U8") in accordance with sections 26 and 92 of the German Social Code (Book V) as retrospectively recorded by the Public Health Service ("Öffentlicher Gesundheitsdienst") of the German Province of Saxony-Anhalt during school entry medical examinations. Also we wanted to analyse the additional variables recorded per child in the areas of social factors, diagnostic findings and levels of therapeutic care in connection with their degree of participation in the preventive medical examinations. METHODOLOGY: The statistical analysis of 73 628 anonymised data sets from the health monitoring system of the German Province of Saxony-Anhalt that were collected by the 14 health authorities in Saxony-Anhalt during school entry medical examinations between 2008 and 2012. An analysis of the data for 20 variables per child was performed with regard to the influence of their degree of participation in the U2 to U8 medical examinations using differences in frequency in the examination groups and checking the significance of these differences by means of the chi-squared test. RESULTS: 99-96% of children in Saxony-Anhalt underwent the 5 preventive medical examinations U2-U6. As the children get older, the participation rates decrease (U2=98.7% down to U8=88.5%). By the time the school entry medical examinations are carried out (at an average age of 63 months), 83% of the children have -undergone all 7 preventive medical examinations for children, while 0.4% have not -undergone one single "U" examination. A child's gender has no influence on its parents' decision as to whether or not it should undergo the examinations. The results also reveal that children who attend day care -facilities are significantly more likely to have undergone all of the U examinations (84.8%) than children who are cared for at home (55.1%). CONCLUSION: The retrospective comprehensive collection of data concerning the children's degree of participation in preventive medical examinations using the school entry medical examination is suitable for identifying connections between participation rates and the social factors, diagnostic findings and levels of therapeutic care of the children in question.

[Pilot study of laser-doppler flowmetry measurement of oral mucosa blood flow].

OBJECTIVE: To explore and compare the perfusion pattern of oral mucosa on Han Chinese and Caucasian by laser-doppler flowmetry. METHODS: A cross-sectional study was carried out, in 20 healthy Han Chinese adult subjects (average age: 28.4 years) and 20 healthy Caucasian (average age: 25.3 years) adult subjects, either gender with 10 subjects. Gingival perfusion was evaluated at 8 points (including upper incisor labial gingival, lower incisor labial gingival, palatal mucosa, cheek mucosa) using a laser-doppler flowmetry(O2C, Medizintechnik GmbH, Germany). Each measurement was carried out 25 seconds consisting 5 seconds of fore period and 20 seconds of work period, without pressure. The measurements were taken by two well- trained doctors, each measurement was exammed 3 times by an examiner, and the average value was recorded as final data. Each measurement has 4 parame ters: SpO2(oxygen saturation), rHB (relative amount of hemoglobin), flow (the blood flow of unit interval), and velocity (blood flow velocity). We compared the data by different sites, different genders, and different races. RESULTS: For palatal gingival, the average SpO2 was 77.1%±10.9%, the average rHB 67.8±11.1, and the average flow 194.1±63.7, which presented significant lower values than other oral mucosa. There was no significant difference among other sites. There was some significant difference between the Caucasian and the Han Chinese: the maxillary central incisor oxygen saturation (SpO2) which were averages of 75.6%±8.2% and 70.4%±7.6%; buccal mucosa hemoglobin (rHB) averages of 79.9±5.8 and 83.5±6.6, which had statistical differences. For most measurement points, the oxygen saturation on men was lower than that on women, which had significant difference. CONCLUSION: To investigate microcirculation pattern, oral mucosa can be the good observation site. Laser-doppler flowmetry is a well-documented instrument to survey on microcirculation.There may be differences between the genders in hemoglobin oxygen-binding capacity, which may have some impact on the ability of soft tissue healing. Oral mucosa display more blood perfusion than attached gingival. As the recipient site of gingival graft, maxilla and mandible have slight difference in blood supply.

Material parameters of the reindeer antler for use in dental implant biomechanics.

The survival of dental implants, in particular immediately loaded implants, critically depends on the biomechanical properties of the bone bed surrounding them. In experimental animal investigations of immediately loaded implants the initial stability, implant design as well as stress and strain distributions in the surrounding bone have been extensively studied. It was the aim of this study to investigate the biomechanical properties of the reindeer antler used as a bony tissue surrounding dental implants, in particular the Young's modulus, Poisson's ratio, and further numerical parameters such as mesh density, friction models and the corresponding frictional coefficients and relative velocities for establishing a novel animal model that can be used in the numerical analyses of experimentally investigated antler specimens. The sensitivity of the investigated parameters was analysed based on the close correlation of numerical and experimental results. No obvious influence of the frictional coefficient and/or relative velocity was observed on the implant displacement using a finite element model. Moreover, nearly identical numerical and experimental results were observed for two kinds of implants concerning implant deflection in the x-axis and implant rotation around the y-axis.

Egg dispersal in the acanthocephalan Acanthocephalus dirus: field data.

Among acanthocephalans, eggs are typically dispersed in the feces of definitive hosts. A recent laboratory-based study provided support for the hypothesis that some female acanthocephalans (Acanthocephalus dirus) carry eggs into the environment prior to dispersal. Here, we examined the potential occurrence of this relationship under natural conditions. Using 6 field surveys, we searched the sediment of a local stream to determine whether the bodies of A. dirus females could be located. We recovered the bodies of 24 intact A. dirus individuals from the stream sediment, of which 5 were mature females. All 5 of the mature females contained mature eggs, with 1 female carrying approximately 10,000. These results are consistent with the interpretation that eggs can be dispersed from the bodies of female A. dirus in nature. We also found that there was significant variation in the number of mature eggs present in the females, with 4 of the 5 females carrying fewer than 400 mature eggs. In addition, we recovered approximately 20,000 mature eggs from a fecal pellet that had been expelled from a fish. We propose that eggs may be dispersed both in the feces of definitive hosts and from the bodies of expelled female A. dirus under natural conditions.

Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells.

Mdm2 is the major negative regulator of p53 tumor-suppressor activity. This oncoprotein is overexpressed in many human tumors that retain the wild-type p53 allele. As such, targeted inhibition of Mdm2 is being considered as a therapeutic anticancer strategy. The N-terminal hydrophobic pocket of Mdm2 binds to p53 and thereby inhibits the transcription of p53 target genes. Additionally, the C-terminus of Mdm2 contains a RING domain with intrinsic ubiquitin E3 ligase activity. By recruiting E2 ubiquitin-conjugating enzyme(s), Mdm2 acts as a molecular scaffold to facilitate p53 ubiquitination and proteasome-dependent degradation. Mdmx (Mdm4), an Mdm2 homolog, also has a RING domain and hetero-oligomerizes with Mdm2 to stimulate its E3 ligase activity. Recent studies have shown that C-terminal residues adjacent to the RING domain of both Mdm2 and Mdmx contribute to Mdm2 E3 ligase activity. However, the molecular mechanisms mediating this process remain unclear, and the biological consequences of inhibiting Mdm2/Mdmx co-operation or blocking Mdm2 ligase function are relatively unexplored. This study presents biochemical and cell biological data that further elucidate the mechanisms by which Mdm2 and Mdmx co-operate to regulate p53 level and activity. We use chemical and genetic approaches to demonstrate that functional inhibition of Mdm2 ubiquitin ligase activity is insufficient for p53 activation. This unexpected result suggests that concomitant treatment with Mdm2/Mdmx antagonists may be needed to achieve therapeutic benefit.

[Obligatory vaccination reporting in Saxony-Anhalt. Possibilities and limitations of establishing a computerized vaccination registry]. / Impfmeldepflicht in Sachsen-Anhalt. Möglichkeiten und Grenzen der Entwicklung eines elektronischen Impfregisters.

Vaccination registries are databases intended to assess and manage complete vaccination data of as many individuals as possible in a population under survey. The task of these registries is to identify low vaccination rates on the individual and population level, to enable systems of reminding individuals, to focus vaccination campaigns and to maximize overall vaccination coverage. Saxony-Anhalt is the only federal state of Germany to have a law that prescribes the reporting of vaccinations. Vaccinations of children up to the age of 7 are reported to the regional public health services. However, as the law provides no regulations as to how the data should be registered and processed, the development of a vaccination registry depends entirely on the initiative and cooperation of the "players in vaccination". The key players in vaccination in Saxony-Anhalt have recently created a Vaccination-Committee, which set out to develop the theoretical standards and a software prototype for the establishment of a computerized vaccination registry. Recent developments in the public health reporting system of Saxony-Anhalt (which strives to modernize its computerized assessment of child and adolescent health) are now opening the possibility to integrate the vaccination registry into the commercially available child health software.

Mouse bites dogma: how mouse models are changing our views of how P53 is regulated in vivo.

P53 is a transcription factor that can cause cells to be eliminated by apoptosis or senescent-like arrest upon its activation by irreparable genetic damage, excessively expressed oncogenes, or a broad spectrum of other stresses. As P53 executes life and death decisions, its activity must be stringently regulated, which implies that it is not likely to be controlled by a simple regulatory mechanism involving a binary on-off switch. This brief review will summarize a subset of the new information presented at the 10th P53 workshop in Dunedin, New Zealand in November 2004 as well as very recent publications that provide new insights into the molecular regulators of P53. Data emerging from mouse models provide a fundamentally different view of how P53 is regulated than suggested by more traditional in vitro approaches. The differences between cell culture and mouse models demonstrate the importance of preserving stoichiometric relationships between P53 and its various regulators to obtain an accurate view of the relevant molecular mechanisms that control P53 activity.

c-Myc, genome instability, and tumorigenesis: the devil is in the details.

The c-myc oncogene acts as a pluripotent modulator of transcription during normal cell growth and proliferation. Deregulated c-myc activity in cancer can lead to excessive activation of its downstream pathways, and may also stimulate changes in gene expression and cellular signaling that are not observed under non-pathological conditions. Under certain conditions, aberrant c-myc activity is associated with the appearance of DNA damage-associated markers and karyotypic abnormalities. In this chapter, we discuss mechanisms by which c-myc may be directly or indirectly associated with the induction of genomic instability. The degree to which c-myc-induced genomic instability influences the initiation or progression of cancer is likely to depend on other factors, which are discussed herein.

[Tooth extraction under medication with acetylsalicylic acid]. / Zahnextraktionen unter Medikation mit Acetylsalicylsäure (ASS).

PURPOSE: The purpose of this prospective study was to show and analyze the bleeding complications after teeth extraction under therapy with 100 mg acetylsalicylic acid (ASA) and to compare them to bleeding complications after teeth extraction in patients with a healthy blood profile. PATIENTS AND METHODS: In 65 patients under medication with 100 mg ASA and in 252 healthy patients, 151/ 543 teeth were extracted and the bleeding complications monitored. RESULTS: The postoperative bleeding frequency was 1.54% in the ASA 100 group and 1.59% in the healthy control group without any medication. No serious or uncontrollable postoperative bleedings arose in either group. All bleedings could be easily handled. No obvious difference concerning the bleeding frequency between the two groups was observed. The small number of bleeding events and the complexity of affecting parameters did not permit statistical tests. CONCLUSION: It is not necessary to interrupt the medication of 100 mg acetylsalicylic acid given to prevent thromboembolism before tooth extractions.

Case Report. Maxillary sinus infection due to Emericella nidulans.

Fungal infections of the maxillary sinus are frequently caused by Aspergillus species, particularly A. fumigatus. In otherwise healthy persons there is an association with overfilling of dental root canals, when zinc-containing filling materials were used. Below, a maxillary sinus aspergilloma is reported in a young immunocompetent female patient caused by Aspergillus (Emericella) nidulans.

Expression of filarial-specific IgG subclasses under different transmission intensities in a region endemic for loiasis.

Specific IgG subclasses were investigated in two villages (Okoumbi and Ndjokaye) in southeast Gabon with different Loa loa transmission intensities of approximately 9,000 and 1,300 infective larvae (L3) per person per year, respectively. IgG subclasses were measured by an enzyme-linked immunosorbent assay (ELISA) using extracts of L. loa L3, microfilariae (MF), or adult worms. Levels of L3-specific IgG3 were significantly higher in the village with low transmission (Ndjokaye) (P = 0.006). In contrast, MF-specific IgG2 was significantly higher in Okoumbi than in Ndjokaye (P = 0.0009). In the high-transmission village (Okoumbi), levels of both MF- and adult-specific IgG4 were significantly increased in MF carriers compared with amicrofilaremic subjects (P = 0.0015 and P = 0.003, respectively), while levels of L3- and MF-specific IgG1 were significantly higher in amicrofilaremic individuals compared with MF carriers (P = 0.04 and P = 0.03, respectively). Furthermore, among microfilaremic individuals, the level of the specific IgG1 subclass was much lower in Okoumbi than in Ndjokaye (P = 0.036). These results suggest that the expression of antigen-specific IgG3 and IgG2 is more likely to vary with transmission intensity, whereas antigen-specific IgG4 and IgG1 varies with adult worm and MF burden.

Coupling of mitotic chromosome tethering and replication competence in epstein-barr virus-based plasmids.

The Epstein-Barr virus (EBV) replicates once per cell cycle and segregates with high efficiency yet does not encode the enzymes needed for DNA replication or the proteins required to contact mitotic spindles. The virus-encoded EBNA-1 (EBV nuclear antigen 1) and latent replication origin (oriP) are required for both replication and segregation. We developed a sensitive and specific fluorescent labeling strategy to analyze the interactions of both EBNA-1 with viral episomes and viral episomes with host chromosomes. This enabled investigation of the hypothesis that replication and chromosome tethering are linked through the EBNA-1 protein. We show that deleting EBNA-1 or oriP disrupts mitotic chromosome tethering but removing the dyad symmetry element of oriP does not. Microscopic and biochemical approaches demonstrated that an EBNA-1 mutant lacking residues 16 to 372 bound to oriP plasmids but did not support their mitotic chromosome association and that the mutant lost the ability of wild-type EBNA-1 to associate with interphase chromatin. Importantly, the transient-replication abilities of various mutant forms of EBV plasmids, including the mutant form with the EBNA-1 internal deletion, correlated directly with their chromosome-tethering abilities. These data lead us to propose that EBNA-1 recruits oriP-containing plasmids into chromatin subdomains in interphase nuclei to both engage the host replication machinery and enable the plasmids to adhere to host chromosomes to increase their segregation efficiency.

Mitotic segregation of viral and cellular acentric extrachromosomal molecules by chromosome tethering.

Mitotic chromosome segregation is mediated by spindle microtubules attached to centromeres. Recent studies, however, revealed that acentric DNA molecules, such as viral replicons and double minute chromosomes, can efficiently segregate into daughter cells by associating with mitotic chromosomes. Based on this similarity between viral and cellular acentric molecules, we introduced Epstein-Barr virus vectors into cells harboring double minute chromosomes and compared their mitotic behaviors. We added lac operator repeats to an Epstein-Barr virus vector, which enabled us to readily identify the transgene in cells expressing a fusion protein between the lac repressor and green fluorescent protein. Unexpectedly, we found that Epstein-Barr virus vectors integrated into the acentric double minute chromosomes, but not into normal chromosomes, in all of the six stably transfected clones examined. While transiently transfected Epstein-Barr virus vectors randomly associated with wheel-shaped prometaphase chromosome rosettes, the chimeras of double minute chromosomes and Epstein-Barr virus vectors in stably transfected clones always attached to the periphery of chromosome rosettes. These chimeric acentric molecules faithfully represented the behavior of native double minute chromosomes, providing a tool for analyzing their behavior in living cells throughout the cell cycle. Further detailed analyses, including real-time observations, revealed that double minute chromosomes appeared to be repelled from the spindle poles at the same time that they attached to the chromosome periphery, while centromeric regions were pulled poleward by the attached microtubules. Disrupting microtubule organization eliminated such peripheral localization of double minute chromosomes, but it did not affect their association with chromosomes. The results suggest a model in which double minute chromosomes, but not Epstein-Barr virus vectors, are subject to the microtubule-mediated antipolar force, while they both employ chromosome tethering strategies to increase their segregation to daughter cells.

The evolution of diverse biological responses to DNA damage: insights from yeast and p53.

The cellular response to ionizing radiation provides a conceptual framework for understanding how a yeast checkpoint system, designed to make binary decisions between arrest and cycling, evolved in a way as to allow reversible arrest, senescence or apoptosis in mammals. We propose that the diversity of responses to ionizing radiation in mammalian cells is possible because of the addition of a new regulatory control module involving the tumour-suppressor gene p53. We review the complex mechanisms controlling p53 activity and discuss how the p53 regulatory module enables cells to grow, arrest or die by integrating DNA damage checkpoint signals with the response to normal mitogenic signalling and the aberrant signalling engendered by oncogene activation.