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OBJECTIVE: There are 500 million patients living with diabetes mellitus worldwide and 50% of them remain undiagnosed. Routine periodontal probing provides gingival crevicular blood in patients with gingivitis. Gingival blood may be useful for diabetes screening without the need for any expensive, painful or time-consuming method by using convenient glucometers. Therefore, the objective of this systematic review and meta-analysis is to answer the question to "is there a difference in glucose or HbA1c levels (O) in patients with positive gingival bleeding (P) measured on gingival crevicular blood (GCB) (I) compared to finger prick capillary blood (CB) (C). MATERIALS AND METHODS: The authors performed an electronic search of six databases using identical MeSH phrases. Only human clinical studies without limitations on the year of publication were considered. Data extraction was done by using standardized data collection sheets. Risk of bias assessment were conducted using QUADAS-2 and QUADAS-C. Meta-analyses were carried out with the random effects model to aggregate the correlation coefficients and the difference between the means between gingival and capillary blood reading, using 95% confidence intervals. RESULTS: The database and manual search yielded 268 articles, from which the selection procedure provided 36 articles for full-text screening, and the final pool of eligible articles composed of 23 studies with 1680 patients. Meta-analysis results on glycemic levels showed differences between the GCB and CB procedures in patients with and without diabetes with values of -6.80 [-17.35; 3.76] and - 4.36 [-9.89; 1.18], respectively. Statistically significant correlations were found (p = 0.001) between GCB and CB measurements in patients with (0.97 [0.927; 0.987]) and without diabetes (0.927 [0.873; 0.958]). CONCLUSION: Gingival blood could prove to be useful to identify patients with undiagnosed diabetes when the necessary amount of uncontaminated blood is present. However, this technique is limited by the possibility of contamination, prandial status and inaccuracies, so it is unsuited to address the patient's glycemic control accurately.
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Glicemia , Líquido do Sulco Gengival , Hemoglobinas Glicadas , Humanos , Hemoglobinas Glicadas/análise , Glicemia/análise , Líquido do Sulco Gengival/química , Reprodutibilidade dos Testes , Diabetes Mellitus/sangueRESUMO
BACKGROUND: Coarctation of the aorta (CoA) is a congenital disease with an incidence of 4 out of 10,000 live births, therefore proper education of its treatment is essential. Understanding the disease and the wide array of treatment options is often difficult. Additive manufacturing technology can be used to produce 3D printed hands-on surgical training tools (HOSTT), which can be used for the education and practical training of CoA. This study aimed to investigate the effectiveness of a 3D printable HOSTT for the simulation of coarctation surgery, and it' possible role in practical education. METHODS: Participants were medical students of Semmelweis University between the second and sixth academic year. A virtual 3D model of an aorta with CoA was generated from a computed tomography angiography scan. Each participant received a 3D-printed aorta phantom and performed either one of four surgical treatment modalities. The simulated surgeries included end-to-end anastomosis, end-to-side anastomosis, prosthetic patch, and subclavian flap aortoplasty. Participants provided feedback, evaluating their understanding of the disease and its treatment by the four surgical reconstruction modalities on a seven-point Likert scale before and after the sessions. RESULTS: 21 medical students participated in this study. Participants' average rating of their understanding of CoA disease and it treatment options before practical training was 4.62 ± 1.07. After training, their average rating increased to 6.19 ± 1.08, showing statistically significant difference. CONCLUSIONS: Within this study's limitations, the applied HOSTT, manufactured using 3D printing, was effective for the practical training of CoA's surgical treatment methods for medical students.
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Impressão Tridimensional , Procedimentos Cirúrgicos Vasculares , Humanos , Projetos Piloto , Estudos de Viabilidade , Simulação por ComputadorRESUMO
STATEMENT OF PROBLEM: Minimally invasive treatments have gained popularity in recent years. However, research comparing the fracture resistance of lithium disilicate partial coverage veneer restorations with that of ceramic crowns is lacking. PURPOSE: The purpose of this in vitro study was to evaluate and compare the fracture resistance of lithium disilicate restorations fabricated for preparations of various designs. The designs included veneer preparations with finish lines in the upper, middle, and lower third of the facial surface and ceramic crown preparations with margins in the lower third of the facial surface. All restorations were designed and fabricated using a chairside digital workflow. MATERIAL AND METHODS: Four maxillary right central incisor typodont teeth were prepared for partial coverage veneer preparation with the margin in the upper middle third of the facial surface (PU1/3); partial coverage veneer preparation with margin in lower middle third of the facial surface (PL1/3); complete coverage veneer preparation (CV) with margin in the cervical region; and ceramic crown (CC) preparation. Each preparation was scanned, and 15 casts were 3D printed from each scan. A total of 60 lithium disilicate restorations were fabricated (n=15 per group) using a chairside computer-aided design and computer-aided manufacturing (CAD-CAM) system (Primescan and MCXL). The different restorations were cemented to the 3D printed testing dies with a photopolymerizable resin cement. The specimens were artificially aged with 10 000 thermal cycles between 5 and 55 °C with a dwell time of 30 seconds and were loaded to failure using a universal testing machine. The maximum load to fracture was analyzed using a 1-way ANOVA and post hoc Tukey honestly significant difference (HSD) test (α=.05). Additionally, the fracture patterns of the specimens were evaluated with a stereomicroscope for descriptive purposes. RESULTS: The mean fracture resistance of the chairside CAD-CAM lithium disilicate veneers and ceramic crowns was statistically different depending on the design of the restoration (P<.05). Group CC demonstrated the highest fracture resistance values (1440.66 N), followed by CV (929.8 N) and PU1/3 (756.13 N). The lowest value was for PL1/3 (532.4 N). CONCLUSIONS: The fracture resistance measured for the maxillary central incisor partial coverage veneers with margins in the middle third of the facial surface appear capable of resisting average occlusal forces. However, these veneers demonstrated lower fracture resistance values when compared with complete coverage veneers. Further, lithium disilicate crowns demonstrated higher fracture resistance than veneers, irrespective of their design.
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Cerâmica , Coroas , Porcelana Dentária , Planejamento de Prótese Dentária , Facetas Dentárias , Incisivo , Humanos , Análise do Estresse Dentário , Falha de Restauração Dentária , Maxila , Desenho Assistido por Computador , Técnicas In VitroRESUMO
OBJECTIVE: There are more than one million children and adolescents living with type 1 diabetes mellitus, and their number is steadily increasing. Diabetes affects oral health through numerous channels, including hyposalivation, immune suppression, and the inflammatory effect of glycation end-products. However, patients with type 1 diabetes must follow a strict sugar free diet that is proven to be carioprotective. Therefore, the aim of this systematic review and meta-analysis is to investigate whether children with type 1 diabetes have a difference in Decayed, Missing, Filled Teeth index (DMFT), salivary function, and periodontal status than children without diabetes, with an emphasis on glycemic control. MATERIALS AND METHODS: PubMed, Embase and Cochrane libraries were screened for articles, using predefined search keys without any language or date restrictions. Two independent authors performed the selection procedure, extracted data from the eligible articles, carried out a manual search of the reference lists, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analysis was performed in R using the random-effects model. Effect sizes were mean differences; subgroup analysis was performed on glycemic control. RESULTS: 33 studies satisfied the eligibility criteria. 22 studies did not show a significant difference regarding the DMFT index between the diabetes and non-diabetes groups; six studies found that children living with diabetes had higher DMFT scores, compared to five studies that found significantly lower scores. Meta-analysis found no statistically significant differences in plaque, gingival, and calculus indexes, however it found significant differences in pooled DMFT indexes, and salivary flow rate. Subgroup analysis on glycemic control using DMFT values found significant differences in children with good and poor glycemic control with results of 0.26 (CI95%=-0.50; 1.03) and 1.46 (CI95%=0.57; 2.35), respectively. CONCLUSIONS: Children with poor glycemic control face higher risk of developing caries compared to good control and non-diabetes children. Regular dental check-ups and strict control of glycemic levels are highly advised for children living with type 1 diabetes, further emphasizing the importance of cooperation between dentists and diabetologists.
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Diabetes Mellitus Tipo 1 , Controle Glicêmico , Saúde Bucal , Criança , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Índice CPORESUMO
Rehabilitation of the edentulous maxilla with implant-supported fixed dental prostheses can represent a significant clinical challenge due to limited bone availability and surgical access, among other factors. This review addresses several treatment options to replace missing teeth in posterior maxillary segments, namely the placement of standard implants in conjunction with maxillary sinus floor augmentation, short implants, tilted implants, and distal cantilever extensions. Pertinent technical information and a concise summary of relevant evidence on the reported outcomes of these different therapeutic approaches are presented, along with a set of clinical guidelines to facilitate decision-making processes and optimize the outcomes of therapy.
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Implantes Dentários , Arcada Edêntula , Boca Edêntula , Levantamento do Assoalho do Seio Maxilar , Humanos , Implantação Dentária Endóssea , Maxila/cirurgia , Planejamento de Prótese Dentária , Boca Edêntula/cirurgia , Prótese Dentária Fixada por Implante , Arcada Edêntula/reabilitação , Resultado do TratamentoRESUMO
Background: The application of blood concentrates has gained popularity in dentistry in recent years. Platelet-rich fibrin (PRF) has been discussed frequently due to a high content of growth factors and the option of chair-side manufacturing in a simple centrifugation process. PRF is free from adjuvants and inexpensive to produce. The number of studies reporting beneficial effects of PRF in various clinical applications such as alveolar ridge preservation, sinus floor elevation, management and prevention of medical-related osteonecrosis of the jaw, third molar extractions, and guided bone regeneration in dentistry has increased recently. However, to date, neither clinical recommendations nor guidelines are available. The present narrative review aims to summarize the level of evidence on the clinical application of PRF within the field of oral surgery and implantology. Summary: A literature search in Pubmed and Medline has identified 34 articles as a basis for this narrative review. The effectiveness of the clinical application of PRF has been analyzed for five indications within dentistry: medical-related osteonecrosis of the jaw, wisdom tooth extraction, guided bone regeneration, sinus floor elevation, and alveolar ridge preservation. The amount of data for third molar extractions, socket preservation, and guided bone regeneration is extensive. Less data were available for the use of PRF in combination with sinus floor elevations. There is a lack of studies with scientific evidence on PRF and medical-related osteonecrosis of the jaw; however, studies positively impact patient-related outcome measures. Most studies report on beneficial effects when PRF is additionally applied in intrabony defects. There is no evidence of the positive effects of PRF combined with bone graft materials during sinus floor elevation. However, some benefits are reported with PRF as a sole filling material. Key Messages: Many recently published studies show the positive clinical impact of PRF. Yet, further research is needed to ensure the validity of the evidence.
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We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on Streptococcus mutans. The systematic search was performed in three databases (Cochrane Library, EMBASE, and PubMed) and included English-language randomized-controlled trials to compare the efficacy of chitosan in reducing the number of S. mutans. To assess the certainty of evidence, the GRADE tool was used. Mean differences were calculated with a 95% confidence interval for one outcome: bacterial counts in CFU/mL. The protocol of the study was registered on PROSPERO, registration number CRD42022365006. Articles were downloaded (n = 6758) from EMBASE (n = 2255), PubMed (n = 1516), and Cochrane (n = 2987). After the selection process, a total of four articles were included in the qualitative synthesis and three in the quantitative synthesis. Our results show that chitosan reduced the number of bacteria. The difference in mean quantity was -4.68 × 105. The interval of the random-effects model was [-2.15 × 106; 1.21 × 106] and the prediction interval was [1.03 × 107; 9.40 × 106]. The I2 value was 98% (p = 0.35), which indicates a high degree of heterogeneity. Chitosan has some antibacterial effects when used as a component of chewing gum, but further studies are needed. It can be a promising antimicrobial agent for prevention.
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Anti-Infecciosos , Quitosana , Cárie Dentária , Humanos , Streptococcus mutans , Saliva/microbiologia , Quitosana/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Goma de MascarRESUMO
Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-d][1]benzazepin-6(5H)-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1-phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield.
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Poly(ethyleneimine) (PEI) is a weakly basic, synthetic, polycationic polymer, due to the presence of primary, secondary, and tertiary amino groups. The amino groups are responsible for the variety of applications of PEI (e.g., transfection, bioimaging, solar cell, etc.). Our study presents some new and reproducible methods for the quantification of molecular or mass concentration of highly branched PEI of different molecular weights (800-2000-25,000-750,000 MW PEI). In the course of the direct method, spectrophotometry and fluorometry were applied to determine the absorption and fluorescence of PEI dilution series. An increase in the MW at the same concentration produces a higher count number because of the higher number of amino groups in PEI molecules. The character of increment in fluorescence intensity is essentially different in the case of mass concentrations and molar concentrations. The increment of the fluorescence intensity related to the molar concentration is non-linear. In the case of mass concentration, the slope is linear. Moreover, their fluorescence is enhanced with the decrease in pH values. The spectrophotometry is a reliable method for measuring the quantity of PEI molecules in solution. Our data help in recognizing the detailed properties of PEI in dendrimer research.
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Dendrímeros/química , Fluorescência , Polietilenoimina/química , Aziridinas/química , Cátions/química , Concentração de Íons de Hidrogênio , Peso Molecular , Polímeros/químicaRESUMO
BACKGROUND: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship. AIMS: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C). EPIDEMIOLOGY: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes. MECHANISMS: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-ß, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression. INTERVENTIONS: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months, although studies involving longer-term follow-up are inconclusive. CONCLUSIONS: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis.
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Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Doenças Periodontais/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Humanos , Resistência à Insulina , Doenças Periodontais/diagnóstico , Doenças Periodontais/etiologia , Doenças Periodontais/terapia , Periodontite/complicações , Periodontite/etiologiaRESUMO
INTRODUCTION: Data proves that Hungary has a leading role in the statistics of oral cancer and patients living with type 2 diabetes. AIM: Our aim was to understand the statistical correlation between oral cancer and metabolic disorder (diabetes mellitus and impaired fasting glucose) due to the valuable data from the Semmelweis University. METHOD: We analyzed the data of 835 patients diagnosed with malignant oral cancer and 587 tumor-free control patients. We investigated the incidence and location of oral cancer among patients living with diabetes, and compared these datasets with our previous data from 14 years earlier. RESULTS: We found that in oral cancer patients, 26.1% had diabetes and 20.8% had impaired fasting glucose; in the control group these ratios were 10.8% and 11.1%. This difference is significant (p<0.05). 14 years ago in the tumor group 14.6%, in the control group 5.6% had diabetes, while 9.7% and 5.5% had impaired fasting glucose. Lip cancer had the biggest incidence. CONCLUSIONS: The rise of type 2 diabetes in the tumor group was significant. This could be a burden for the health care system. We want to highlight the importance of interdisciplinary cooperation between health care professionals. Orv Hetil. 2018; 159(20): 803-807.
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Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Bucais/epidemiologia , Adulto , Carcinoma de Células Escamosas/epidemiologia , Comorbidade , Feminino , Seguimentos , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de RiscoRESUMO
Our research is focused on the incidence of diabetes mellitus and glucose metabolic disorders among oral cancer patients and the frequency of different oral localizations of cancer. Diabetes mellitus affects 7% of the Hungarian population. This study uses data spanning 14 years, with 2 datasets of 1998-1999 and 2012-2013, collected first hand by the authors. These datasets have led us to examine the blood glucose level in 267 patients with histologically confirmed malignant tumours in the oral cavity. Diabetes mellitus was found in 59 of them (22.1%), The blood glucose was elevated in 32 cases (12%). The most frequent tumor locations among the diabetic patients: labial, lingual and gingival tumors gingivae. Comparative epidemiological study demonstrates that in 2012-2013 dataset there was an increased observed percentage of people with diabetes mellitus [17.6% to 22.1%]. The percentage of patients with IFG (impaired fasting glucose) also increased from 9.8% to 12%. Overall the number of patients with glucose metabolic disorders climbed from 27.4% to 34.1%, (p > 0.05). Our intention of this introductory analysis is to emphasize the close connection of these two very important disease groups, and the wider spread of diabetes mellitus.
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Diabetes Mellitus/epidemiologia , Neoplasias Bucais/epidemiologia , Adulto , Idoso , Glicemia/metabolismo , Distribuição de Qui-Quadrado , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Neoplasias Gengivais/epidemiologia , Humanos , Hungria/epidemiologia , Incidência , Neoplasias Labiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Estresse Oxidativo , Prevalência , Fatores de Risco , Fatores de Tempo , Neoplasias da Língua/epidemiologiaRESUMO
OBJECTIVE: The aim of this research was to collate and analyse the data on the oral health knowledge and the related habits of a Hungarian cohort of monozygotic (MZ) and dizygotic (DZ) twins using the newly developed World Health Organisation Oral Health Questionnaire for Adults (Annex 7). METHOD: A total of 15 sets of MZ twins and 14 sets of DZ twins (58 individuals) aged between 18 and 71 years were enrolled in the study. Each participant had to fill out a web-based questionnaire which comprised 23 questions (Google Forms). The data were collated and the oral health/hygiene habits of MZ and DZ twins were compared. RESULTS: No significant differences were detected between MZ and DZ twins with regards to their daily tooth-cleaning habits or the tooth-cleaning products used by the 2 groups. For instance, when asked how often they clean their teeth, 80% of MZ twins and 71% of DZ twins responded similarly. Further, both groups provided similar responses when questioned about the use of fluoride toothpaste, frequency of dental visits, and dental counselling received as well as a number of other parameters such as snacking of sweets and fear of visiting dentists. CONCLUSIONS: Our pilot analysis of the questionnaire responses from MZ and DZ twins in Hungary did not indicate any significant differences in their oral care habits in general. Further studies with a large cohort are required to confirm or refute our findings.
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Saúde Bucal , Gêmeos Dizigóticos , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Projetos Piloto , Hungria , HábitosRESUMO
This case report aimed to describe a rare benign mandibular tumour and assess the outcomes of the most recent reviews, between January 2017 and August 2023. Presenting a detailed clinical case, this study advances our understanding of the diagnostic and therapeutic aspects, ultimately improving the management of similar cases in clinical practice. Orthopantomogram (OPG) revealed a well-defined unilocular radiolucency extending from the midline of the ramus and teeth 47 and 48 were submerged at the base of the mandible. In the presented case, a PLANMECA ROMEXIS PROMAX® three-dimensional (3D) maximum (MAX) cone-beam computed tomography (CBCT) device was used for the 3D examination. An intraoral approach was preferred and the tumour was removed in toto by creating a bone window using a W&H® Dentalwerk Bürmoos GmbH Piezomed piezoelectric device, and the bone plates were fixed with 4 MEDARTIS® microplates, with a primary flap closure. A PANORAMIC 1000, 3DHISTECH Ltd® device was employed for the histological investigation. Odontogenic tumours are rare and typically asymptomatic, often discovered incidentally during routine radiographic examinations. Most of these benign lesions heal well after complete excision and require long-term follow-up. Once diagnosed, ameloblastic fibroma (AF) should be treated immediately to avoid malignant transformation.
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OBJECTIVE: The study answers the PECO question: "In adults with dental implants (P), do subjects suffering from type-2 diabetes or prediabetes (E) have worse peri-implant conditions (O) than subjects without type-2 diabetes and prediabetes (C)?". Prediabetes (5.7-6.4 % HbA1c), and the different qualities of glycemic control in type-2 diabetes; well-controlled (>8 % HbA1c), and poorly controlled (>8 % HbA1c) individuals; were classified according to the recommendations of the American Diabetes Association. DATA: Predefined search keys were used with search terms including: Dental implant, diabetes mellitus, glycemic control and HbA1c. SOURCES: An electronic search in the MEDLINE, Embase, and Cochrane libraries were conducted without any filters or language restrictions. Additionally, manual search of the reference lists were carried out to identify all relevant articles. STUDY SELECTION: Eligibility criteria were cohort, case-control and cross-sectional studies that answerd our PECO question with at least 1 year of follow-up. From a total of 2660 records, 35 articles (1761 individuals) were included in the analysis. Meta-analytic difference in means for crestal bone loss was 1.2 mm [95 % CI=0.4; 2.1] in patients with prediabetes, 1.8 mm [CI=1.0; 2.7] in poorly controlled patients, whereas 0.4 mm [CI=-0.3; 1.1] in well-controlled individuals. Meta-regression showed that 1 % increase in HbA1c increased crestal bone loss by 0.24 mm. CONCLUSIONS: Within the limitations of the study, patients with poorly controlled type-2 diabetes or prediabetes may have worse peri-implant conditions compared to patients without diabetes and well-controlled type-2 diabetes. Well-controlled type-2 diabetes is not a risk indicator for peri-implant diseases. CLINICAL SIGNIFICANCE: Clinicians should measure blood HbA1c levels when planning implant-supported restorations, thus patients with undiagnosed or poorly controlled type-2 diabetes can be identified, that allows for glycemic level adjustment prior to dental implant surgery, ensuring peri-implant health. PROTOCOL REGISTRATION NUMBER: (CRD42022375263).
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Implantes Dentários , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Estado Pré-Diabético/sangue , Implantes Dentários/efeitos adversos , Hemoglobinas Glicadas/análise , Fatores de Risco , Peri-Implantite/etiologia , Controle GlicêmicoRESUMO
The development of copper(II) thiosemicarbazone complexes as potential anticancer agents, possessing dual functionality as inhibitors of R2 ribonucleotide reductase (RNR) and tubulin polymerization by binding at the colchicine site, presents a promising avenue for enhancing therapeutic effectiveness. Herein, we describe the syntheses and physicochemical characterization of four isomeric proligands H2L3-H2L6, with the methylmorpholine substituent at pertinent positions of the pyridine ring, along with their corresponding Cu(II) complexes 3-6. Evidently, the position of the morpholine moiety and the copper(II) complex formation have marked effects on the in vitro antiproliferative activity in human uterine sarcoma MES-SA cells and the multidrug-resistant derivative MES-SA/Dx5 cells. Activity correlated strongly with quenching of the tyrosyl radical (Yâ¢) of mouse R2 RNR protein, inhibition of RNR activity in the cancer cells, and inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity, supported by experimental results and molecular modeling calculations, are presented.
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Antineoplásicos , Cobre , Morfolinas , Ribonucleotídeo Redutases , Tiossemicarbazonas , Tubulina (Proteína) , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/síntese química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ribonucleotídeo Redutases/antagonistas & inibidores , Ribonucleotídeo Redutases/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Morfolinas/farmacologia , Morfolinas/química , Morfolinas/síntese química , Cobre/química , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Polimerização/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Ensaios de Seleção de Medicamentos Antitumorais , Modelos MolecularesRESUMO
The spectral characteristics of monosubstituted derivatives of 2,2'-bithiophene (1-BT) with simple carbonyl substituents, including -COCF3 (trifluoroacetyl, 2-BTCF), -COCH2CN (oxopropanenitrile, 3-BTCN) and -COCH3 (acetyl, 4-BTCE), and the more complex 5'-((9H-fluoren-9-ylidene)methyl)-3-methyl, 5-methyl carboxylate (5-BTFL) were investigated. Absorption and fluorescence spectra and fluorescence lifetimes were measured in solvents with various polarities and compared with those in polymer matrices (polystyrene, PS; polymethyl methacrylate, PMMA; and polyvinyl chloride, PVC). Although the parent, 1-BT, absorbed near 300 nm and exhibited no or weak fluorescence, the substitution of 1-BTwith simple substituents at position 5 resulted in a bathochromic shift of approximately 50 nm or more in absorption and distinct fluorescence above 400 nm. The largest shift in absorption and fluorescence was observed for the complex 5-BTFL with fluorene as a substituent for 1-BT. The most intense fluorescence was observed for the derivative 2-BTCF with trifluoroacetyl as a substituent in the polar PVC matrix. The lifetimes of fluorescence of all substituted 2,2'-bithiophenes were in the range from 0.3 to 3 ns. The polymer matrices increased the intensity of fluorescence to some extent and prolonged the lifetime of the 2,2'-bithiophene derivatives. The reasons for the variation in the fluorescence intensity resulting from the substitution of the parent dimer are discussed.
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Reactions of 5-tert-butyl-2-hydroxy-3-methylsulfanylbenzaldehyde S-methylisothiosemicarbazone and 5-tert-butyl-2-hydroxy-3-phenylsulfanylbenzaldehyde S-methylisothiosemicarbazone with pentane-2,4-dione (Hacac) and triethyl orthoformate in the presence of M(acac)2 as template source at 107 °C afforded metal complexes of the type M(II)L(1) and M(II)L(2), where M = Ni and Cu, with a new Schiff base ligand with thiomethyl (H2L(1)) and/or thiophenyl (H2L(2)) group in the ortho position of the phenolic moiety. Demetalation of NiL(1) in CHCl3 with HCl(g) afforded H2L(1). The latter reacts with Zn(OAc)2·2H2O with formation of ZnL(1). The effect of -SR groups and metal ion identity on stabilization of phenoxyl radicals generated electrochemically was studied in detail. A marked stabilization of phenoxyl radical was observed in one-electron-oxidized complexes [ML(2)](+) (M = Ni, Cu) at room temperature, as demonstrated by cyclic voltammetry, EPR spectroscopy, and UV-vis-NIR measurements. In solution, the oxidized CuL(2) and NiL(2) display intense low-energy NIR transitions consistent with their classification as metal-delocalized phenoxyl radical species. While the CuL(2) complex shows reversible reduction, reduction of NiL(2), CuL(1), and NiL(1) is irreversible. EPR measurements in conjunction with density functional theory calculations provided insights into the extent of electron delocalization as well as spin density in different redox states. The experimental room temperature spectroelectrochemical data can be reliably interpreted with the (3)[CuL(2)](+) and (2)[NiL(2)](+) oxidation ground states. The catalytic activity of synthesized complexes in the selective oxidations of alcohols has been studied as well. The remarkable efficiency is evident from the high yields of carbonyl products when employing both the CuL(2)/air/TEMPO and the CuL(2)/TBHP/MW(microwave-assisted) oxidation systems.
Assuntos
Complexos de Coordenação/química , Galactose Oxidase/química , Oxigênio/química , Fenóis/química , Catálise , Cobre/química , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Ligantes , Modelos Moleculares , Níquel/química , Oxirredução , Espectrofotometria Ultravioleta , Zinco/químicaRESUMO
PURPOSE: To assess the clinical performance of a two-piece zirconia implant system, with a focus on biologic complications. MATERIALS AND METHODS: A total of 39 patients received 91 two-piece zirconia implants. The patients were recruited from two private clinics and were monitored for 5 to 12 years (median: 5.6 years). The primary outcomes were biologic complications, such as peri-implant infections (peri-implant mucositis and peri-implantitis), and the secondary outcome was radiographically evident marginal bone loss (MBL). RESULTS: Three patients (7.7%) with 9 total implants (9.9%) presented with peri-implant mucositis. MBL that did not exceed the first thread was evident at 32 mesial sites (35%) and 25 distal sites (27.4%). MBL exceeding the first thread but not the third thread was evident at 6 mesial and 5 distal sites (thread pitch: 0.7 mm). Only one peri-implant pocket deepened (4 mm) and showed bleeding; however, the estimated MBL did not exceed 1.65 mm. No peri-implantitis occurred, and no implant was lost. CONCLUSIONS: This prospective study shows high survival rates and a seemingly low prevalence of biologic and prosthetic complications for this two-piece zirconia implant system over an observation period of up to 12 years.
Assuntos
Perda do Osso Alveolar , Produtos Biológicos , Implantes Dentários , Mucosite , Peri-Implantite , Humanos , Implantes Dentários/efeitos adversos , Estudos Prospectivos , Peri-Implantite/etiologia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologiaRESUMO
INTRODUCTION: This article describes the authors' digital workflow-based method for fabricating intraoral occlusal splints, from planning to the evaluation phase. MATERIALS AND METHODS: In our protocol, first, we had a registration phase. This included taking digital impressions, determining the centric relation (CR) position with the deprogrammer Luci Jig, and using the digital facebow for measuring the individual values. The laboratory phase was next, which included planning and manufacturing with a 3D printer. The last phase was delivery, when we checked the stability of the splint and adjusted the occlusal part. RESULT: The average cost is lower for a fully digital splint than for conventional methods. In terms of time, there was also a significant difference between the classic and digital routes. From a dental technical point of view, the execution was much more predictable. The printed material was very rigid and, therefore, fragile. Compared to the analog method, the retention was much weaker. CONCLUSION: The presented method permits time-efficient laboratory production, and may also be performed chairside in a dental office. The technology is perfectly applicable to everyday life. In addition to its many beneficial properties, its negative properties must also be highlighted.