Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.

OBJECTIVE: To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate. MATERIALS AND METHODS: A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts. RESULTS: Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate. CONCLUSIONS: The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate. CLINICAL RELEVANCE: Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

Comparative metabolic analysis in head and neck cancer and the normal gingiva.

OBJECTIVES: Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients. MATERIALS AND METHODS: Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters. RESULTS: There were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient. CONCLUSIONS: We could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage. CLINICAL RELEVANCE: The aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.

Amplified morphogenetic and bone forming activity of amorphous versus crystalline calcium phosphate/polyphosphate.

Amorphous Ca-phosphate (ACP) particles stabilized by inorganic polyphosphate (polyP) were prepared by co-precipitation of calcium and phosphate in the presence of polyP (15% [w/w]). These hybrid nanoparticles showed no signs of crystallinity according to X-ray diffraction analysis, in contrast to the particles obtained at a lower (5% [w/w]) polyP concentration or to hydroxyapatite. The ACP/15% polyP particles proved to be a suitable matrix for cell growth and attachment and showed pronounced osteoblastic and vasculogenic activity in vitro. They strongly stimulated mineralization of the human osteosarcoma cell line SaOS-2, as well as cell migration/microvascularization, as demonstrated in the scratch assay and the in vitro angiogenesis tube forming assay. The possible involvement of an ATP gradient, generated by polyP during tube formation of human umbilical vein endothelial cells, was confirmed by ATP-depletion experiments. In order to assess the morphogenetic activity of the hybrid particles in vivo, experiments in rabbits using the calvarial bone defect model were performed. The particles were encapsulated in poly(d,l-lactide-co-glycolide) microspheres. In contrast, to crystalline Ca-phosphate (containing only 5% [w/w] polyP) or to crystalline ß-tricalcium phosphate, amorphous ACP/15% polyP particles caused pronounced osteoinductive activity already after a six-week healing period. The synthesis of new bone tissue was accompanied by an intense vascularization and an increased expression of mineralization/vascularization marker genes. The data show that amorphous polyP-stabilized ACP, which combines osteoinductive activity with the ability to act as a precursor of hydroxyapatite formation both in vitro and in vivo, is a promising material for bone regeneration.

Pelvic floor and abdominal muscle cocontraction in women with and without pelvic floor dysfunction: a systematic review and meta-analysis.

There is an ongoing discussion regarding abdominal muscle (AbM) and pelvic floor muscle (PFM) synergism. Therefore, this study aimed to investigate the cocontraction between AbMs and PFMs in women with or without pelvic floor dysfunction (PFD). The following databases were searched up to December 21, 2018: MEDLINE, EMBASE, LILACS, PEDro and CENTRAL. We included any study that assessed the cocontraction between PFMs and AbMs in women with and without PFD. Two reviewers independently screened eligible articles and extracted data. The outcomes were extracted and analyzed as continuous variables with random effect models. Twenty studies were included. A meta-analysis did not show differences in women with and without PFD. However, a sensitivity analysis suggested cocontraction of the transversus abdominis (TrA) during PFM contraction in healthy women (standardized mean difference (SMD) -1.02 [95% confidence interval (CI) -1.90 to -0.14], P=0.02; I2= not applicable; very low quality of evidence). Women with PFD during contraction of PFMs showed cocontraction of the obliquus internus (OI) (SMD 1.10 [95% CI 0.27 to 1.94], P=0.01; I2= not applicable; very low quality of evidence), and obliquus externus (OE) (SMD 2.08 [95% CI 1.10 to 3.06], P<0.0001; I2 = not applicable; very low quality of evidence). Increased cocontraction of the TrA may be associated with maximal contraction of PFMs in women without PFD. On the other hand, there is likely an increased cocontraction with the OI and OE in women with PFD.

Herbal medications for anxiety, depression, pain, nausea and vomiting related to preoperative surgical patients: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To summarise the effects of herbal medications for the prevention of anxiety, depression, pain, and postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgical procedures. METHODS: Searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and LILACS up until January 2018 were performed to identify randomised controlled trials (RCTs). We included RCTs or quasi-RCTs evaluating any herbal medication among adults undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgeries. The primary outcomes were anxiety, depression, pain and PONV. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence for each outcome. RESULTS: Eleven trials including 693 patients were eligible. Results from three RCTs suggested a statistically significant reduction in vomiting (relative risk/risk ratio (RR) 0.57; 95% CI 0.38 to 0.86) and nausea (RR 0.69; 95% CI 0.50 to 0.96) with the use of Zingiber officinale (ginger) compared with placebo in both laparoscopic and obstetrical/gynaecological surgeries. Results suggested a non-statistically significantly reduction in the need for rescue medication for pain (RR 0.52; 95% CI 0.13 to 2.13) with Rosa damascena (damask rose) and ginger compared with placebo in laparoscopic and obstetrical/gynaecological surgery. None of the included studies reported on adverse events (AEs). CONCLUSIONS: There is very low-certainty evidence regarding the efficacy of both Zingiber officinale and Rosa damascena in reducing vomiting (200 fewer cases per 1000; 288 fewer to 205 fewer), nausea (207 fewer cases per 1000; 333 fewer to 27 fewer) and the need for rescue medication for pain (666 fewer cases per 1000; 580 fewer to 752 more) in patients undergoing either laparoscopic or obstetrical/gynaecological surgeries. Among our eligible studies, there was no reported evidence on AEs. PROSPERO REGISTRATION NUMBER: CRD42016042838.

Herbal medications for surgical patients: a systematic review protocol.

INTRODUCTION: Postoperative nausea and vomiting (PONV) affect approximately 80% of surgical patients and is associated with increased length of hospital stay and systemic costs. Preoperative and postoperative pain, anxiety and depression are also commonly reported. Recent evidence regarding their safety and effectiveness has not been synthesised. The aim of this systematic review is to evaluate the efficacy and safety of herbal medications for the treatment and prevention of anxiety, depression, pain and PONV in patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgical procedures. METHODS AND ANALYSIS: The following electronic databases will be searched up to 1 October 2016 without language or publication status restrictions: CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgeries and managed with herbal medication versus a control group (placebo, no intervention or active control) prophylactically or therapeutically will be considered eligible. Outcomes of interest will include the following: anxiety, depression, pain, nausea and vomiting. A team of reviewers will complete title and abstract screening and full-text screening for identified hits independently and in duplicate. Data extraction, risk of bias assessments and evaluation of the overall quality of evidence for each relevant outcome reported will be conducted independently and in duplicate using the Grading of Recommendations Assessment Development and Evaluation classification system. Dichotomous data will be summarised as risk ratios; continuous data will be summarised as standard average differences with 95% CIs. ETHICS AND DISSEMINATION: This is one of the first efforts to systematically summarise existing evidence evaluating the use of herbal medications in laparoscopic, obstetrical/gynaecological and cardiovascular surgical patients. The findings of this review will be disseminated through peer-reviewed publications and conference presentations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042838.

Use of cyanoacrylate for the stabilization of tissues in root coverage procedures: A case series report with 5 years follow up

ABSTRACT: A variety of periodontal plastic surgery techniques have been proposed to correct aesthetic and functional problems caused by gingival recession, with root coverage using connective tissue grafts being the one most commonly performed. These surgeries, however, are partially dependent on tissue graft stability. In this case series, we describe the use of a tissue adhesive (cyanoacrylate) as a solution for graft stabilization. Two patients with Cairo's type 1 gingival recession were treated with an envelope technique using connective tissue graft stabilized with cyanoacrylate alone. The results were a faster procedure and complete root coverage, even after 5 years of follow-up. Our findings suggest that cyanoacrylates can be an alternative to standard graft stabilizing procedures, leading to a stable root coverage in RT1 recessions.

Impact of Soft Tissue Pathophysiology in the Development and Maintenance of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ).

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ), numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates, nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Further, the cell architecture and expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP-related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Use of dermal matrices to change gingival phenotypes

ABSTRACT: A variety of periodontal plastic surgery techniques have been proposed to correct aesthetic and functional problems of periodontal tissues. The most common procedure uses the connective tissue graft from the palate. However, patient discomfort and the limited quantity of palatal tissue results in many cases where the surgeon uses connective tissue substitutes. In this case report, we describe the use of a human dermal matrix for gingival volume augmentation in the lower incisors with a novel modified VISTA technique stabilizing the flap with sutures and cyanoacrylates, avoiding comorbidity of a second surgical site. The follow up at 6 months showed an increase in gingival thickness and a reduction in recessions length.

Técnica de enceramento incremental: anteriores superiores / Incremental waxing technique

O conhecimento detalhado da anatomia dentária é peça-chave para a formação de um cirurgião-dentista qualificado. Para desenvolver a capacidade de escuta e percepção de detalhes, o enceramento diagnóstico é um dos métodos mais completos. Quanto mais fidedigno o enceramento diagnóstico for, mais amplo será o aprendizado proporcionado por ele. Dessa maneira, a técnica incremental de enceramento demonstrada neste artigo proporciona a reconstrução do elemento dentário desde a região interna, respeitando as cores e espessuras do esmalte e da dentina, até a porção superficial do esmalte, amplamente caracterizada...

The detailed knowledge of dental anatomy is an essential piece for the formation of a qualifed dental surgeon. To develop the sculpture capacity and perception of details, diagnostic waxing is one of the most complete ways. The more faithful the diagnostic waxing is, better the exercise will be. With that thought in mind, the incremental technique demonstrated in this article enables the reconstruction of the dental element initially from the internal region, respecting the colors and widths of enamel and dentin, up to the enamel surface, very characterized.

Provisórios anteriores maquiados e estratificados / Anteriors temporary maquiated and stratified

Para corresponder tecnicamente ao crescente apelo estético de nossos pacientes, obtendo resultados consistentes, é fundamental que sejamos previsíveis. A maneira de atingirmos essa previsibilidade passa pela padronização dos porcedimentos. Através do enceramento diagnóstico e subsequente preparação de provisórios, conseguimso testar nossa propostas de tratamento e perceber seus acertos e falhas, permitindo a participação ativa de nosso paciente. Com essas informações, aq posterior aplicação cerâmica fica grandemente simplificada, bastando ao técnico reproduzir o que já foi acordado entre o cirurgião-dentista e o paciente.

To technically meet the growing aesthetic appeal of our patients, and to obtain consistent results, it is essential for us to be predictable. The way to achieve this predictability is the standardization of procedures. Through the diagnostic waxing and subsequent preparation of temporaries, we test the proposed treatment and realize its successes and failures, allowing the active participation of our patient. With this information, the subsequent application of the ceramic is greatly simplified, and the technician simply reproduces what has already been agreed between dentist and patient.

Técnica incremental para resinas compostas - anteriores superiores / Incremental technique for composite resins - upper anterior teeth

O conhecimento detalhado da anatomia dentária é peça chave para a formação de um cirurgião-dentista qualificado. O material mais apropriado para um primeiro contato com os conceitos da anatomia dentária é certamente a cera. Esse material proporciona ao cirurgião-dentista o desenvolvimento da motricidade fina e da percepção de detalhes de forma, função e estética. A resina composta, material de uso frequente nos consultórios odontológicos, exige muito mais técnica para ser aplicada corretamente e para que seu potencial seja adequadamente explorado. Tendo em vista que a técnica de enceramento incremental já foi entendida e praticada, este protocolo de aplicação de resina composta é o passo subsequente, visto que os mesmos princípios aplicados à cera serão demonstrados em resina composta.