Objectives
Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is an adverse side effect of long-term bisphosphonate treatment. One theory of BP-ONJ etiology suggests a negative influence of ...these agents on angiogenesis and vascularization. This in vivo study analyzed the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay.
Materials and methods
Matrigel plugs were implanted into fifty 6–8-week-old female nude mice. Ten animals each were treated either with clodronate, ibandronate, pamidronate, zoledronate, or carrier solution as controls. The microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in Matrigel plugs were analyzed after 21 days of treatment by immunohistochemistry and exemplary 3D microvascular corrosion castings.
Results
All bisphosphonates induced a statistically significant decrease of MVD (
p
each <0.001), whereby the nitrogen-containing bisphosphonates (N-BPs) demonstrated a clearly stronger effect than non-nitrogen-containing bisphosphonates (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm
2
). Referring to MVA, similar results could be detected. MVS was significantly increased especially by ibandronate (103 %) compared to control group (
p
< 0.001). Scanning electron microscope scans of the corrosion castings confirmed these results.
Conclusions
The stronger influence on MVD by N-BPs compared to the NN-BP clodronate may explain for the lack of BP-ONJ after treatment with NN-BPs.
Clinical relevance
Ibandronate induced a strong increase of MVS. In combination with the reduced MVD, this could result only in a fractional reduced perfusion which might be an explanation for the lower occurrence of BP-ONJ in patients receiving ibandronate compared to patients receiving pamidronate or zoledronate.
Background
The number of people living with dementia worldwide is increasing rapidly. Preventive approaches constitute a promising strategy to counter the dementia epidemic, and growing numbers of ...lifestyle interventions are conducted around the globe. Gender differences with respect to modifiable risk factors for dementia have been reported, however, little is known about gender-specific effectiveness of lifestyle trials against cognitive decline and dementia. A systematic review and meta-analysis was conducted to assess evidence on gender-specific design and effectiveness of randomized controlled trials against cognitive decline.
Methods
Systematic literature searches were conducted in MEDLINE, PsycINFO, Web of Science, Cochrane Central and ALOIS. Studies assessing global and/or domain-specific cognitive function in older adults free from dementia were eligible for the systematic review. We assessed between-group effect sizes using random-effects meta-analysis. Methodological quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN)-checklist.
Results
The systematic review and meta-analysis included 34 and 31 studies, respectively. Effects of lifestyle-interventions on global cognition were non-significant overall (g =.27; 95% CI: −.01;.56) and in male subsamples (g = −.05; 95% CI: −.55;.45), and small for female subsamples (g =.38; 95% CI:.05;.72). Small beneficial effects were found for memory (overall: g =.38; 95% CI =.17;.59). Stratified by gender, significant effects were observed only in women (g =.39; 95% CI =.13;.65; men: g =.37; 95% CI:.00;.73). Aspects of gender in study design and conduct were discussed in a small minority of studies. Comparable results were observed for executive function and verbal fluency. Methodological quality was deemed high in 17.6% of studies, acceptable and low quality in 52.9% and 29.4%, respectively.
Discussion
We found evidence for small differences in the effectiveness of lifestyle interventions on global cognition and memory in favor of women. However, small numbers of trials 1) targeting men and 2) reporting gender-specific results for older adults with mild cognitive impairment warrant further attention. Assessing differences in modifiable risk factors for dementia in men and women and systematically addressing aspects of gender in trial conduction and recruitment in future studies might increase knowledge on gender-specific effectiveness of lifestyle trials against cognitive decline.
Objectives
This study investigated the influence of three CAD/CAM zirconia ceramics for implant-abutment manufacturing on cell viability, migration ability, and cytotoxicity of human gingival ...fibroblasts (HGF) and oral keratinocytes (HOK) in vitro.
Materials and methods
HGF and HOK were cultured on zirconia ceramic disks (VITA In-Ceram YZ, Ivoclar IPS e.max ZirCAD, Sirona inCoris ZI) and on control disks made of tissue culture polystyrene. Cell viability was analyzed by a MTT assay. Migration ability was detected by a scratch assay. A ToxiLight assay was used to analyze the influence of the tested zirconia ceramics on adenylate kinase (ADK) release and cytotoxicity.
Results
At MTT assay, HGF showed an increased cell viability compared to the control after 9 and 12 days for all ceramics (
p
each ≤0.0002) while HOK demonstrated a decreased cell viability after 9 and 12 days for all ceramics (
p
each ≤0.0003). At scratch assay, HGF exhibited for all ceramics decreased relative distances of the scratch wound compared to the control from 24 to 48 h (
p
each <0.0001) with exception of VITA In-Ceram YZ after 48 h. HOK showed increased distances compared to the control for all ceramics after 48 h (
p
each <0.0001). At ToxiLight assay, a minimal cytotoxicity of the tested materials could be detected.
Conclusions
Overall, significant influences of the investigated CAD/CAM zirconia ceramics on HGF and HOK could be shown.
Clinical relevance
The analyzed zirconia ceramics could influence oral soft-tissue cells that might affect the esthetic outcome after implant placement using CAD/CAM zirconia abutments.
Objectives
Geranylgeraniol (GGOH) has been reported as a potential treatment option for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ). The aim of this study was to analyze the effects ...of GGOH on endothelial progenitor cells (EPC) after bisphosphonate treatment in vitro.
Materials and methods
EPC were incubated with different nitrogen (N-BPs: ibandronate, pamidronate, zoledronate) and a non-nitrogen-containing bisphosphonates (NN-BP: clodronate) with and without GGOH. Cell viability was measured by MTT and PrestoBlue assay. Migration ability was analyzed with a Boyden and Scratch assay. Apoptosis rates were determined by colony-forming, Tunel and ToxiLight assays.
Results
Negative effects of N-BPs on EPC were shown in all tests without GGOH. The substitution of GGOH demonstrated significantly increased cell viability (MTT:
p
each N-BP ≤0.004; PrestoBlue:
p
each N-BP <0.001) and migration ability (Boyden:
p
each N-BP <0.001; Scratch:
p
each N-BP <0.001). Concerning the apoptosis rates, increased EPC colony densities (
p
each N-BP ≤0.009), decreased numbers of apoptotic cells in the Tunel assay (
p
each N-BP <0.001), and a decreased adenylate kinase release in the ToxiLight assay (
p
each N-BP ≤0.03) were observed. For the clodronate-treated cells, no significant differences could be detected with or without GGOH in any assay (
p
each N-BP/NN-BP >0.05).
Conclusions
GGOH cell treatment reversed the negative effects of bisphosphonates on EPC.
Clinical relevance
These findings support the hypothesis that systemic or local GGOH treatment might lead to new therapeutic strategies for BP-ONJ.
Objectives
Recent studies focused on angiogenesis in the pathophysiology of bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and identified geranylgeraniol (GGOH) as a feasible option for ...BP-ONJ therapy. This study investigated the influence of GGOH on microvessel sprouting after BP-incubation in vitro.
Materials and methods
Ten experimental set-ups were randomly designed in an in vitro 3D-angiogenesis assay. Two groups included HUVEC cell spheroids with and without (±) GGOH substitution as controls and eight groups pairwise contained either clodronate or the nitrogen-containing bisphosphonates (N-BP) ibandronate, pamidronate, and zoledronate ± GGOH. The size of the cell spheroids including the outbranching sprouts (SpS) as well as the density (SpD) and length of the sprouts (SpL) were analyzed by a grid system after 0, 24, 48, and 72 h.
Results
For controls and NN-BP clodronate, no significant differences at any tested parameter and any point of measurement could be detected within the experimental set-ups ± GGOH (
p
each ≥0.05). For N-BP ibandronate, the experimental set-ups +GGOH showed a significantly increased SpS, SpD, and SpL after 48 and 72 h (
p
each ≤0.002) compared to the experimental set-ups −GGOH. For N-BPs pamidronate and zoledronate, the experimental set-ups + GGOH demonstrated a significantly increased SpS, SpD, and SpL after 24, 48, and 72 h (
p
each ≤0.001) compared to the experimental set-ups −GGOH.
Conclusions
The strong negative influence of N-BPs on microvessel sprouting could be significantly reversed by GGOH.
Clinical relevance
Since supportive therapeutic options for BP-ONJ are lacking, GGOH might be a promising substitute for BP-ONJ prevention and therapy.
Objectives
The reproducibility of electronic color-measuring devices used in dentistry refers to the consistency of measurements of a single device and also that between identical devices. This in ...vitro study evaluated the short-term interdevice agreement of eight equivalent dental measurement devices.
Methods
The short-term repeatability of eight identical VITA Easyshade Advance color measurement devices was evaluated. Each device was used to quantify the Commission Internationale de l’Eclairage (CIE)
L
*
a
*
b
* color coordinates of ceramic disks, designed in accordance with guidelines set by the VITA Toothguide 3D-Master shade tab organization. Statistical analysis involved calculating the intraclass correlation coefficients (ICCs) and color differences (Δ
E
*) for corresponding measurements taken by the devices. In addition, the mean color difference from the mean (MCDM) was calculated for each color.
Results
All devices showed high ICCs for the color coordinates (
L
= 0.996,
a
= 0.993,
b
= 0.999). The Δ
E
* by shade ranged from 0.62 to 1.67. The MCDM by color-measuring device ranged from 0.11 to 0.23.
Conclusion
This in vitro study showed that the color-measuring devices used were suitable for determining shade with high repeatability.
Clinical relevance
The high interdevice agreement of the VITA Easyshade Advance means that dental professionals can use this device independently, without compromising the consistency and quality of color measurements.
Background
The aim of this study was to measure the oral health-related quality of life (OHRQoL) after maxillary sinus augmentation to determine the physical and psychological impact of this ...procedure for the patient.
Methods
Three hundred sixteen patients treated with an external or internal maxillary sinus augmentation and a total of 863 implants in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between July 2002 and December 2007 were included in this retrospective study. Total implant survival was assessed. Completion of a modified 26-item version of the Oral Health Impact Profile (OHIP-G) for assessing the oral health-related quality of life before and after the treatment was asked for. Subcategories were (1) functional limitations, (2) physical and psychological disabilities, and (3) complaints due to the surgical procedure. In 53 patients available for clinical follow-up examination, assessment of soft tissue parameters was performed.
Results
After an average time in situ of 41.2 ± 27 months (3.4 years), the in situ rate was 95.4%. One-year survival rate and five-year survival rate according to Kaplan Meier were 95.4 and 94.4%. Concerning functional limitations, significant better values for OHRQoL after sinus augmentation procedure than before the treatment (
p
< 0.001) were seen. In the subcategory physical and psychological disabilities, all questions had significant better values after the sinus lift (
p
< 0.001). Concerning complaints due to the surgical procedure, mean total scores were 5.1 ± 5.4 pre-operative, 6.9 ± 6.1 (0–31) post-operative, and 2.4 ± 3.7 recently. This meant a significant difference between “pre-operative” vs. “post-operative” (
p
= 0.003), “pre-operative” vs. “recently” (
p
< 0.001), and “post-operative” vs. “recently” (
p
< 0.001). Concerning the influence of implant indication, edentulous patients showed the most distinct improvement after the procedure. Clinical assessment showed stable soft tissue parameters.
Conclusions
Evaluation of OHRQoL after sinus augmentation showed a significant improvement indicating a remarkable benefit for the patients through this procedure.
The present study compares some phenotypic and physiologic characteristics of microvascular and macrovascular endothelial cells from within one human organ. To this end microvascular endothelial ...cells from human full-term placenta (PLEC) were isolated using a new method and compared with macrovascular human umbilical vein endothelial cells (HUVEC) and an SV-40-transformed placental venous endothelial cell line (HPEC-A2). PLEC were isolated by enzymatic perfusion of small placental vessels, purified on a density gradient and cultured subsequently. Histological sections of the enzyme-treated vessels showed a selective removal of the endothelial lining in the perfused placental cotyledons. The endothelial identity of the cells was confirmed by staining with the endothelial markers anti-von Willebrand factor,
Ulex europaeus lectin and anti-QBEND10. The cells internalized acetylated low-density lipoprotein and did not show immunoreactivity with markers for macrophages, smooth muscle cells and fibroblasts. The spindle-shaped PLEC grew in swirling patterns similar to that described for venous placental endothelial cells. However, scanning electron microscopic examination clearly showed that PLEC remained elongated at the confluent state, in contrast to the more polygonal phenotype of HPEC-A2 and HUVEC that were studied in parallel. The amount of vasoactive substances (endothelin-1,2, thromboxane, angiotensin II, prostacyclin) released into the culture medium and the proliferative response to cytokines was more similar to human dermal microvessels (MIEC) derived from non-fetal tissue than to HUVEC. Potent mitogens such as vascular endothelial growth factors (VEGF
121, VEGF
165) and basic fibroblast growth factor (FGF-2) induced proliferation of all endothelial cell types. Placental growth factors PlGF-1 and PlGF-2 effectively stimulated cell proliferation on PLEC (142±7% and 173±10%) and MIEC (160±20% and 143±28%) in contrast to HUVEC (9±8% and 15±20%) and HPEC-A2 (15±7% and 24±6%) after 48 h incubation time under serum-free conditions. These data support evidence for (
1) the microvascular identity of the isolated PLEC described in this study, and (
2) the phenotypic and physiologic heterogeneity of micro- and macrovascular endothelial cells within one human organ.
Abstract There is a gender-related comorbidity of pain-related and inflammatory bowel diseases with psychiatric diseases. Since the impact of experimental gastrointestinal inflammation on the ...emotional-affective behavior is little known, we examined whether experimental gastritis modifies anxiety, stress coping and circulating corticosterone in male and female Him:OF1 mice. Gastritis was induced by adding iodoacetamide (0.1%) to the drinking water for at least 7 days. Inflammation was assessed by gastric histology and myeloperoxidase activity, circulating corticosterone determined by enzyme immunoassay, anxiety-related behavior evaluated with the elevated plus maze and stress-induced hyperthermia tests, and depression-like behavior estimated with the tail suspension test. Iodoacetamide-induced gastritis was associated with gastric mucosal surface damage and an increase in gastric myeloperoxidase activity, this increase being significantly larger in female mice than in male mice. The rectal temperature of male mice treated with iodoacetamide was enhanced, whereas that of female mice was diminished. The circulating levels of corticosterone were reduced by 65% in female mice treated with iodoacetamide but did not significantly change in male mice. On the behavioral level, iodoacetamide treatment caused a decrease in nocturnal home-cage activity, drinking and feeding. While depression-related behavior remained unaltered following induction of gastritis, behavioral indices of anxiety were significantly enhanced in female but not male mice. There was no correlation between the estrous cycle and anxiety as well as circulating corticosterone. Radiotracer experiments revealed that iodoacetamide did not readily enter the brain, the blood–brain ratio being 20:1. Collectively, these data show that iodoacetamide treatment causes gastritis in a gender-related manner, its severity being significantly greater in female than in male mice. The induction of gastritis in female mice is associated with a reduction of circulating corticosterone and an enforcement of behavioral indices of anxiety. Gastric inflammation thus has a distinct gender-dependent influence on emotional-affective behavior and its neuroendocrine control.
Objectives
The aim of this study was to analyze the influence of four CAD/CAM all-ceramic materials on cell viability, migration ability and adenylate kinase (ADK) release of human gingival ...fibroblasts (HGF) and oral keratinocytes (HOK).
Materials and methods
HGF and HOK were cultured on disc-shaped CAD/CAM all-ceramic materials (e.max CAD LT, e.max CAD HT, Empress CAD and Mark II) and on discs made of tissue culture polystyrene surface (TCPS) serving as control. Cell viability was analyzed by using an MTT assay, and migration ability was investigated by a scratch assay. A ToxiLight assay has been performed to analyze the effect of all-ceramic materials on ADK release and cell apoptosis.
Results
At MTT assay for HGF, no significant decrease of cell viability could be detected at all points of measurement (
p
each > 0.05), while HOK demonstrated a significant decrease in cell viability especially on Empress CAD and Mark II at each point of measurement (
p
each < 0.001). Scratch assay demonstrated an increased migration ability for HGF on e.max CAD HT, Empress CAD and Mark II (
p
each < 0.001), whereas HOK showed a significantly decreased migration ability on all tested materials at all points of measurement (between −36 % and −71 %;
p
each < 0.001). At ToxiLight assay, only small cytotoxic effects of the all-ceramic materials could be investigated.
Conclusions
This study disclosed significant differences in cell viability and migration ability of HGF and HOK on CAD/CAM all-ceramic materials.
Clinical Relevance
CAD/CAM all-ceramic materials can influence oral cell lines responsible for soft tissue creation which may affect the esthetic outcome.
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