Influence of surgical ultrasound used in the detachment of flaps, osteotomy and odontosection in lower third molar surgeries. A prospective, randomized, and "split-mouth" clinical study.

BACKGROUND: As third molar surgery is the most commonly procedure performed in Dentistry and has been accompanied by serious postoperative disorders such as pain, edema and trismus, the study aimed to evaluate if ultrasound device would be able to reduce such postoperative features. The aim of this study was to assess the effects of soft tissue flap elevation, osteotomy and odontosection using piezosurgery versus conventional technique in mandibular third molar extractions. MATERIAL AND METHODS: Twenty patients with impacted mandibular third molars underwent tooth extractions using two different methods. Ten patients were included in the Piezo Flap Group (PFG - the flap was elevated using piezosurgery) and ten patients were part of the Piezo Ostectomy Group (POG - osteotomy and odontosection were carried out with ultrasound tips). The contralateral tooth was included in the Control Group (CG - conventional technique). The patients were evaluated at postoperative periods of 1, 3, 7 and 14-days. The measured parameters were duration of surgery, pain, trismus and swelling. RESULTS: The mean duration of surgery for the PFG was 17.21 minutes (CG 10.07 minutes) and POG was 40.09 minutes (CG 15.97 minutes). There was no statistically significant difference in pain and trismus for any of the postoperative periods evaluated in PFG and POG (p>0.05). There was a statistically significant difference in swelling between the PFG and POG, presenting less swelling at the 3-day postoperative period (p=0.038; p<0,05). However, for the remaining analyzed periods there was no difference (p>0.05). CONCLUSIONS: Piezosurgery for tissue elevation of the surgical flap, osteotomy and dental sectioning in mandibular third molar extraction surgery promoted less edema in the early postoperative stages in mandibular third molar extractions despite the longer surgical duration.

Alveolar repair after the use of piezosurgery in the removal of lower third molars: a prospective clinical, randomised, double-blind, split-mouth study.

The objective of this study was to evaluate the use of piezosurgery for osteotomy and odontosection in the repair of the alveoli four months after exodontia. Fifteen young patients who needed third molars extracted were included. During the extractions, one of the teeth was included in the Piezo group, in which ultrasound motor tips were used in both procedures. The other tooth was removed with a conventional rotary instrument. The values of density of the repair regions of the right and left third molars were compared using digital panoramic radiographs. There were no significant differences (p>0.05): piezo group mean (SD) 125.7 (15.4) and control group 126.7 (21.2). The bone density of the alveoli after extraction of the lower third molars with rotary instruments and surgical ultrasound was similar in both groups.

Periodontal status of individuals with Down syndrome: sociodemographic, behavioural and family perception influence.

BACKGROUND: The aim of the present study was to assess the periodontal condition of individuals with Down syndrome and the association with sociodemographic and behavioural characteristics and family perception of oral health. METHODS: This cross-sectional observational study was performed at a referral centre for dental assistance to disabled persons in Araçatuba, Brazil. Parents of the individuals were interviewed, and the visible plaque index, bleeding on probing, probing pocket depth and clinical attachment level were recorded by one periodontist in six sites per tooth of all teeth. The individual was the unit of analysis. The significance level was set at 5%. RESULTS: Sixty-four subjects (23.8 ± 8.3 years old) were included. Eighteen (28.1%) were diagnosed with gingivitis and 46 (71.9%) with periodontitis. In the multiple logistic regression final model, age and self-reported oral hygiene practices were associated with the occurrence of periodontitis. The chance of having periodontitis was 4.7 times higher among individuals older than 20 years and approximately 4 times higher in patients whose oral hygiene was performed by themselves and their parents, compared with those who performed oral hygiene alone. Sex, follow-up time in the centre, education, degree of participants' dependence, flossing and family history of periodontal disease were not associated with the occurrence of periodontitis. Higher levels of plaque and bleeding were observed for participants with parents reporting bad gingival health (76.2% and 46.9%) and deficient oral hygiene (79.5% and 47.3%). The perception of parents regarding gingival bleeding was correlated with higher bleeding detected clinically (P = 0.01; 50.1%). CONCLUSIONS: The prevalence of periodontitis in individuals with Down syndrome is high and increases with age, even in the face of the parents' perception about their children's oral condition.

Regulatory systems in bone marrow for hematopoietic stem/progenitor cells mobilization and homing.

Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

Colon cancer therapy: recent developments in nanomedicine to improve the efficacy of conventional chemotherapeutic drugs.

The number of patients with colorectal cancer, the third most frequently diagnosed malignancy in the world, has increased markedly over the past 20 years and will continue to increase in the future. Despite recent advances in chemotherapy, currently used anticancer molecules are unable to improve the prognosis of advanced or recurrent colorectal cancer, which remains incurable. The transport of classical drugs by nanoparticles has shown great promise in terms of improving drug distribution and bioavailability, increasing tissue half-life and concentrating anticancer molecules in the tumor mass, providing optimal drug delivery to tumor tissue, and minimizing drug toxicity, including those effects associated with pharmaceutical excipients. In addition, colon cancer targeting may be improved by incorporating ligands for tumor-specific surface receptors. Similarly, nanoparticles may interact with key drug-resistance molecules to prevent a reduction in intracellular drug levels drug. Recently published data have provided convincing pre-clinical evidence regarding the potential of active-targeted nanotherapeutics in colon cancer therapy, although, unfortunately, only a few of these therapies have been translated into early-phase clinical trials. As nanotechnology promises to be a new strategy for improving the prognosis of colon cancer patients, it would be very useful to analyze recent progress in this field of research. This review discusses the current status of nanoparticle-mediated cancer-drug delivery, the challenges restricting its application, and the potential implications of its use in colon cancer therapy.

Predictive value of stabilometry and fear of falling on falls in postmenopausal women.

OBJECTIVES: Falls are one of the leading causes of fractures and impaired quality of life in the elderly, and they are related to balance deficit and to fear of falls. The purpose of our study is to evaluate predictors of falls in the 50-65-year-old postmenopausal population. METHODS: A prospective cohort study was conducted on 96 postmenopausal women. Fear of falling and postural stability were assessed by using the FES-I (Falls Efficacy Scale-International) and a force platform, respectively. Fall frequency was determined in the 12-month follow-up study period. Multivariate logistic regression was used to identify predictive factors of falls. RESULTS: Fear of falls, the FES-I scale and four stabilometric parameters, specifically under eyes-closed condition, were significantly higher in the group of fallers. The root mean square amplitude in the medial-lateral direction with eyes closed (RMSXec) (odds ratio 5.1, 95% confidence interval (CI) 1.6-15.5, p = 0.004) and FES-I (odds ratio 3.4, 95% CI 1.1-10.5, p = 0.026) were the best independent predictive factors of the risk of falling. CONCLUSIONS: RMSXec > 0.133 was the best predictive factor for falls in our group of 50-65-year-old postmenopausal women studied, and a FES-I score > 20 could predict falls in this population.

How is gene transfection able to improve current chemotherapy? The role of combined therapy in cancer treatment.

Despite advances in cancer treatment, a large number of patients eventually develop metastatic disease that is generally incurable. Systemic chemotherapy remains the standard treatment for these patients. Several chemotherapeutic combinations have proven effective in the management of cancer. Paradoxically, although the purpose of polychemotherapy is to improve the prognosis and prolong the survival of patients, it often carries considerable toxicity that causes substantial adverse symptoms. For this reason, a major goal of cancer research is to improve the effectiveness of these cytotoxic agents and reduce their adverse effects. Gene transfer has been proposed as a new strategy to enhance the efficacy of anti-tumor drugs in the treatment of intractable or metastatic cancers. In fact, the association of gene therapy and drugs (combined therapy) has been reported to increase the anti-proliferative effect of classical treatments in lung, bladder, pancreatic, colorectal and breast cancers, among others. Various especially promising therapies have been proposed in this context, including the use of suicide genes, antisense oligonucleotides, ribozymes and RNA interference. In this chapter, we review recent progress in the development of novel anti-cancer strategies that associate cytotoxic agents with gene transfer to enhance their antitumor effect.

Synergistic antitumoral effect of combination E gene therapy and Doxorubicin in MCF-7 breast cancer cells.

The low effectiveness of conventional therapies to achieve the long-term survival of metastatic breast cancer patients calls for the development of novel options. Genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the antiproliferative activity of drugs. Combined therapy using these genes and classical antitumoral drugs are under intensive study. The E gene from ϕX174 encodes a membrane protein with a toxic domain that leads to a decrease in the tumour cell growth rate. With the aim of improving the anti-tumour effect on breast cancer cells of the currently used chemotherapeutic drugs (Paclitaxel, Docetaxel and Doxorubicin), we investigated the association of E suicide gene with these drugs. The effect of the combined therapy (gene therapy and cytotoxic) was determined by treating transfected MCF-7 cells and multicellular tumour spheroids (MTS) with drugs gradient concentrations. Our results showed that E gene has a direct oncolytic effect inducing a significant decrease in the proliferation rate of the MCF-7 cells. The E gene antitumoral activity was mediated by the induction of apoptosis (mitochondrial pathway). In addition, a significant enhancement of proliferation inhibition was observed when E gene transfection was associated with cytotoxic drugs in comparison to single treatments. The use of the combined therapy E gene-Doxorubicin obtained the greatest effect on the MCF-7 growth arrest. This therapeutic association also induced a significant enhancement of the MTS volume growth inhibition. Anti-tumour activity of the chemotherapeutic drugs classically used in the treatment of breast cancer was enhanced by E gene. Our in vitro results indicate that experimental therapeutic strategy based in the combined therapy E gene and cytotoxic drugs may be of potential therapeutic value as a new strategy for patients with advanced breast cancer.

Tumour malignancy loss and cell differentiation are associated with induction of gef gene in human melanoma cells.

BACKGROUND: Gene therapy is a new method used to induce cancer cell differentiation. Our group previously showed that transfection of the gef gene from Escherichia coli, related to cell-killing functions, may be a novel candidate for cancer gene therapy. Its expression leads to cell cycle arrest unrelated to the triggering of apoptosis in MS-36 melanoma cells. OBJECTIVES: To determine the basis of the antiproliferative effect of the gef gene in this cell line. METHODS: Transmission electron microscopy, apoptosis analysis by confocal microscopy, flow cytometry and immunocytochemical analysis were used. RESULTS: Ultrastructural analysis showed a strikingly different morphology after treatment with dexamethasone and expression of the gef gene, with large accumulations of pigment throughout the cell cytoplasm and presence of melanosomes in different stages of development. High mitochondrial turnover and myeloid bodies, characteristics of neurone cells, were also observed. In addition, both immunocytochemical and indirect immunofluorescence analysis demonstrated a significant decrease in HMB-45, Ki-67 and CD44 antigen expression and an increase in S100 and p53 expression in gef gene-transfected MS-36 melanoma cells that were correlated with the duration of dexamethasone treatment. In the present work, we report that gef gene not only reduces cell proliferation in transfected melanoma MS-36TG cell line but also induces morphological changes clearly indicative of melanoma cell differentiation and a reduction in tumour malignancy. CONCLUSIONS: These findings support the hypothesis that the gef gene offers a new approach to differentiation therapy in melanoma.

Methodology in the European higher education area for the Anatomy learning in the Health Sciences

Development of the European Higher Education Area is linked to the adoption of a new educational model. Thus, in the Health Sciences, basic science knowledge must be integrated with the clinical skills that students will require in their professional activity. The Anatomy and Embryology Teaching Investigation Group at our university (UGR-N-40-UCUA) designed a specific questionnaire to analyse specific items that affect Anatomy learning. It also developed a teaching methodology for the acquisition of anatomic knowledge, integrating theory and practice, including individual and collective tasks for students and leading to future self-learning. Analyses were performed in different groups of first-year students at the School of Medicine of Granada University, School of Nursing of Almería University and School of Physiotherapy of Jaén University. It was found that application of this teaching methodology achieved an improvement in two areas considered essential by these students, i.e. a better understanding of several aspects of the study subject, and greater satisfaction with their acquisition of anatomic and embryologic knowledge (AU)

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Role of the organization of subjects and the educational resources used in their teaching in the Anatomy education-learning process

Within the three-year nursing degree course in Spain, the way in which anatomy teaching is organised shows distinct differences between different universities. At the University of Jaén, first-year students have human anatomy (HA) as a separate subject, whereas at the University of Almeria, anatomy is included within a larger module called the structure and function of the human body (SFHB). The aim of this study was to analyze the reaction of students to the organization of their anatomy courses, the resources used in their teaching, their contents, and the tutoring and evaluation system. For this purpose, a 35-item questionnaire was designed to address aspects related to these objectives and administered at the end of the 2005-6 academic year to 82 students of taking human anatomy at the University of Jaén and 52 students taking structure and function of human body at the University of Almeria. Results obtained showed differences in the evaluation of the educational organization of these subjects at the two universities. The approval rating of Jaen students for the relationship between their theoretical and practical education/training was 25% lower than that of Almeria students. This difference appears to be related to the different distributions of credits between the two subjects in the courses surveyed. Students appeared more highly to value the resources that were most frequently used during the course, suggesting that students may value most highly those resources employed most frequently within a course. There were some similarities between the students at the different universities in the importance they assigned to the different thematic units of the respective subjects. Finally, both groups revealed a preference for face-to-face tutorial sessions and for evaluation by written examinations (AU)

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Anatomy teaching to physiotherapy students: Preliminary study in the European higher education area setting

The integration of the Spanish university system within the European Higher Education Area implies a change in the current educational model towards a more flexible system that establishes the equivalence of degrees and encourages greater competition among courses. In this system, students will be expected to make a greater contribution to real learning in order for it to be more useful in their future professional activity. These changes will involve new student-teacher relationships, new methodologies, new teaching strategies and different evaluation systems. The success of this project will depend on a thorough knowledge of the present state of the courses that we teach. This is the first study to address the current state of human anatomy and embryology learning in the physiotherapy degree course. The analysis was performed in first-year students and focussed on the subject designated the structure and function of the human body, skeletal and muscle system anatomy at the Universities of Almería and Jaén. Student opinions were sought on the appropriateness of these subjects to their degree, on the methods used in practice and theory classes and on the evaluation and tutorial systems. Results obtained were similar between the two universities included in this study and indicated that: 1) students have a good opinion of the usefulness of the subject contents in human anatomy and embryology, 2) students prefer the new technologies to traditional educational systems, and 3) students have a positive appreciation of written examination versus oral examination or continuous continuous assessment. These findings will assist teachers of anatomy and embryology to establish approaches to improve the quality of learning in the setting of the European Higher Education Area (AU)

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Pedagogic evaluation of anatomical teaching for a medical and surgical degree at the University of Granada

Anatomy has been classically considered as a basic foundation for the teaching of medicine, developing a decisive role in medical education and for future professional activity. But, in common with other scientific disciplines, it has grown simultaneously with technology and communication sciences and in a much prescribed manner. The purpose of our study was to estimate different parameters related to the quality of the anatomical teaching at the University of Granada. In trying to achieve this, we have focused on the Human Anatomy I and II courses (given in the first and second years of the medical degree respectively). Once the examinations in these courses were completed, a questionnaire was filled by the students in which they had to estimate, in a one to five range, the adaptation and the adjustment of different aspects related to the development of the course. The results indicated that the students were in favour of practical classes compared to theoretical tuition. On the other hand, the pedagogical organisation of the courses was highly valued by the students, particularly in relation to the adaptation of programme objectives and to the recommended bibliography (both for textbooks and atlases). The best estimated didactic resource for the practical aspect of the subject was the use of human anatomical specimens, and the most favoured procedure in the theoretical classes was the use of the blackboard. For the examinations and assessments, no special preference for any evaluation method was found, but the use of complementary papers (e.g. use of monographs, oral expositions) was considered by the students to be of very little importance (AU)

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Induction of drug resistance in embryonal rhabdomyosarcoma treated with conventional chemotherapy is associated with HLA class I increase.

Effectiveness of conventional cytotoxic treatment of rhabdomyosarcoma (RMS) may be limited by the development of multidrug resistance (MDR) mediated by mdr1 gene. This gene codes for P-glycoprotein (P-gp) which has been related to a immunoregulatory function. Modulation of HLA expression by P-gp has been described in different types of tumor cells including RMS. However, very little is known about biological implications of the P-gp expression in RMS patients treated with conventional chemotherapy. In order to study the problem, we used embryonal RMS tissue samples from treated patients. Our results indicated that positive RMS samples to mdr1 show higher HLA class I expression than those which were negative to mdr1 PCR, what indicates a significant correlation between the expression of both molecules. In addition, we developed two resistant RMS cell lines (A-204-1 and 2) using similar concentrations of actinomycin D as are plasma levels in clinical situation. Both resistant cell lines showed mdr1 expression and an increase of HLA class I expression which was dose-dependent. These results demonstrated that conventional chemotherapy of embryonal RMS is able to induce resistance which can modulate HLA class I expression and suggest that immunological studies of these tumors may be necessary to the design new specific therapeutic strategies.

Release of alpha-actin into serum after skeletal muscle damage.

OBJECTIVE: The skeletal muscle protein alpha-actin was investigated in the serum of subjects with severe skeletal muscle damage to assess its utility as a reliable and predictive marker of muscle damage. METHODS: Serum samples were obtained from 33 healthy controls and 33 patients with severe skeletal muscle damage, defined by a total creatine kinase value of >500 IU/l (Rosalki method). Troponin I, troponin T, and myoglobin concentrations were determined by immunoassay and alpha-actin concentrations by Western blot and densitometry. RESULTS: The mean serum concentration of alpha-actin in controls and patients with skeletal muscle damage was 600.9 and 1968.51 ng/ml, respectively, a statistically significant difference. Sera of patients with muscle damage showed higher levels of alpha-actin than of troponin or myoglobin. No significant difference in troponin I levels was observed between the groups. CONCLUSIONS: According to these results, alpha-actin was the most significant skeletal muscle damage marker analysed and may be an ideal candidate for the identification of all types of myofibre injury, including sports injuries. Our findings support the use of alpha-actin as a marker alongside other currently used biological proteins.

Non-viral and viral vectors for gene therapy.

Human gene therapy can be defined as the delivery of genetic material into a patient's cells with a therapeutic aim. The success or failure of gene therapy depends on the development and efficiency of the transfection of viral and non-viral vectors. Viral vectors typically offer higher transduction efficiency and long-term gene expression, but may be associated with toxicity, immunogenicity, restricted target cell specificity and high cost. Non-viral methods have become widespread because of their relative safety, capacity to transfer large genes, site-specificity and their non-inflammatory, non-toxic and non-infectious properties. However, the clinical usefulness of non-viral methods is limited by their low transfection efficiency and relatively poor transgene expression. In this review, we describe the progress made in the development of gene delivery technology and its possible application in clinical trials.

Cancer gene therapy: strategies and clinical trials.

In recent years, great advances have been made in developing novel therapeutic systems based on the introduction of genetic material into damaged cells and designed to correct the error underlying the disease or destroy the pathological cell. One of the main applications of this new approach, known as gene therapy, is the treatment of malignant pathological tumours, in which classic treatments with radiotherapy, chemotherapy and surgery are only palliative. Strategies developed to date include the use of suicide genes, immunity-enhancing genes, apoptosis-inducing genes or genes that inhibit the neovascularization of the tumour, and the blocking of mutated tumour suppressor genes or their restoration in the tumour cell. The effectiveness shown in cell culture and animal experiments and some promising results in clinical trials suggest that gene therapy will help to improve the prognosis of cancer patients and may become the treatment of choice.

Modulation of Ki-67 expression and morphological changes induced by gef gene in MCF-7 human breast cancer cells.

New therapeutic strategies are required to overcome the limitations of conventional breast cancer treatment. Suicide gene therapy offers a potential approach to this type of tumour, since systems based on the use of prodrugs may present some drawbacks related to toxicity, drug release and bioavailability. The gef gene has cell-killing functions in Escherichia coli and does not depend on the use of a prodrug for its action, making it an attractive target for suicide gene therapy. We created a gef-overexpressing human breast cancer cell line (MCF-7TG) by transfecting the gef gene under the control of a pMAMneo promotor. Dexamethasone-induction of gef gene expression in MCF-7TG cells produced a significant decrease in Ki-67 expression, which is a known proliferation marker. In addition, annexin-V-FITC and propidium iodide assays showed the presence of apoptotic cell death, which was confirmed by scanning electron microscopy. The most significant finding was the presence of "craters" in the cell membrane, as previously described in other apoptotic breast cancer cells. These results demonstrate the ability of the gef gene to down regulate Ki-67 expression and induce apoptosis in a breast cancer cell line, suggesting its potential application as a new gene therapy strategy for this type of tumor.

Antitumoural properties of benzannelated seven-membered 5-fluorouracil derivatives and related open analogues. Molecular markers for apoptosis and cell cycle dysregulation.

Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. We prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and 14-membered aminal structures and acyclic compounds. All the cyclic aminals provoked a G0/G1-phase cell cycle arrest, whereas Ftorafur, a known prodrug of 5-FU, and 1-[2-(2-hydroxymethyl-4-nitrophenoxy)-1-methoxyethyl]-5-fluorouracil (11) induced an S-phase cell cycle arrest. Although breast cancer is most often treated with conventional cytotoxic agents it has proved difficult to induce apoptosis in breast cancer cells, but improved clinical responses may be obtained by identifying therapies that are particularly effective in activating apoptosis. 1-(2,3-Dihydrobenzoxepin-2-yl)-5-fluorouracil (5) may be particularly useful in stimulating apoptosis in breast cancer.

Contractile regulatory proteins tropomyosin and troponin-T as indicators of the modulatory role of retinoic acid.

Retinoic acid (RA), the active metabolite of vitamin A, plays a significant role in regulating cardiac form and function throughout the life of the organism. Both cardiac morphogenesis and myocardial differentiation are affected by alterations in RA homeostasis. In order to test the effect of all-trans RA and 13-cis RA on cardiomyocyte differentiation, we studied the level and the subcellular compartmentalization of alpha-tropomyosin and troponin-T proteins in cultures of chick embryo cardiomyocytes obtained from Hamburger and Hamilton's (HH) stage 22, 32 and 40 embryos. The retinoids increased the levels of alpha-tropomyosin and troponin-T in the cytoplasmic and cytoskeletal fractions of cells at all three stages of development. The greatest increases in alpha-tropomyosin occurred in the cytoplasmic fraction in HH22 cells cultured for 24 h with all-trans RA or 13-cis RA, whereas the greatest increases in troponin-T were found in the cytoplasmic fraction of HH32 cells exposed to retinoids for 24 h. In cultures treated for 48 h with retinoids, the levels of alpha-tropomyosin and troponin-T showed significant increases in the cytoplasmic compartment of cells treated in HH32-with respect to the control values. These findings are further evidence that RA plays a modulating role in the formation and reorganization of sarcomeric proteins during the process of cardiomyocyte maturation.