Gtdap-1 and the role of autophagy during planarian regeneration and starvation

Planarians have been established as an ideal model organism for stem cell research and regeneration. Planarian regeneration and homeostasis require an exquisite balancing act between cell death and cell proliferation as new tissues are made (epimorphosis) and existing tissues remodeled (morphallaxis). Some of the genes and mechanisms that control cell proliferation and pattern formation are known. However, studies about cell death during remodeling are few and far between. We have studied the gene Gtdap-1, the planarian ortholog of human death-associated protein-1 or DAP-1. DAP-1 together with DAP-kinase has been identified as a positive mediator of programmed cell death induced by gamma-interferon in HeLa cells. We have found that the gene functions at the interface between autophagy and cell death in the remodeling of the organism that occurs during regeneration and starvation in sexual and asexual races of planarians. Our data suggest that autophagy of existing cells may be essential to fuel the continued proliferation and differentiation of stem cells by providing the necessary energy and building blocks to neoblasts.

On regeneration and collateral sprouting to hind limb digits after sciatic nerve injury in the rat

This study examines the proportions of regenerative and collateral sprouting to the skin after peripheral nerve injury. Methods: In the first experimental paradigm, primary afferent neurones were pre-labelled with Diamidino Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair. After three months of regeneration, digit 3 was re-injected with Fast Blue (FB) to label regernating cells. Fluoro-Gold (FG) was applied to the femoral (FEM) and musculocutaneous (MC) nervers four days later to quantify their contribution to the innveration. In the second experimental paradigm, sciatic nerve was first sectioned and repaired. Three months later, the sciatic was resected, and digit 3 injected with FB. After four more days, FEM and MC were resected and FG injected in all digits. Results: Neurones in dorsal root ganglion (DRG) L5 had a higher rate of correct reinnervation of digit 3 (44-72%) than neurones in DRG L4 (14-44%). Like in control cases, only occasional axons were traced from the FEM and MC. In the second experiment, only occasional labelled neurones appeared. Conclusions: The results indicate differences in the capacity for correct peripheral sensory reinnvervation between segmental levels and that in this model collateral sprouting was practically non-existent compared to regenerative sprouting.

Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and dental implications

In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient"s medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk assessment

JNK controls the onset of mitosis of planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun-NH2-kinase (JNK) links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal.

Evaluación de la regeneración ósea mediante procesado de imagen

La regeneració òssia és un procés estudiat per experts de tot el món. Aquests experts estudien materials capaços d’accelerar el procés de formació de teixit ossi en zones on s’han produït defectes ossis. Després d’un determinat període de temps de l’aplicació dels materials d’estudi en la zona on hi havia una manca de teixit ossi, s’obtenen imatges d’aquesta zona on l’expert mitjançant l’ inspecció visual d’aquestes imatges avalua si l’os s’ha regenerat bé o no. El problema d’aquest mètode d’avaluació es que requereix d’un expert on la valoració d’aquest és subjectiva i difícil de quantificar, el que pot provocar que hi hagi discordança entre experts. Amb la finalitat de aprofitar les imatges en que es basa l’expert per avaluar la capacitat de regeneració òssia dels materials d’estudi es proposa realitzar un anàlisi quantitatiu de la regeneració òssia basat en el processament d’imatge. L’algorisme dissenyat es capaç de classificar imatges de la mandíbula en: imatges de regeneració bona i dolenta mitjançant la parametrització de l’histograma de nivells de grisos de la imatge, solucionant la falta d’objectivitat del mètode d’avaluació de la regeneració òssia i la necessitat d’un expert per realitzar-la.

BS-SEM evaluation of the tisular interactions between cortical bone and calcium-phosphate covered titanium implants

The improvement of the reliability of the contact between the osseous tissues and the implant materials has been tested by recovering the metallic implants with ceramic materials, usually calcium phosphates. In our study, the calcium phosphate recovering layers were deposited by means of a pulsed-laser deposition technique. Our aim was to to evaluate the tissue interactions established between cortical bone and titanium implants covered by five different layers, ranging from amorphous calcium phosphate to crystalline hydroxyapatite, obtained by altering the parameters of the laser ablation process. The surgical protocol of the study consisted in the simultaneous implantation of the five types of implants in both the tibial dyaphisis of three Beagle dogs, sacrificed respectively one, two and three months after the last surgical procedures. After the sacrifice, the samples were submitted to a scheduled procedure of embedding in plastic polymers without prior decalcification, in order to perform the ultrastructural studies: scanning microscopy with secondary and backscattered electrons (BS-SEM). Our observations show that both in terms of the calcified tissues appearing as a response to the presence of the different coatings and of time of recovering, the implants coated with crystalline calcium phosphate layers by laser ablation present a better result than the amorphous-calcium-phosphate-coated implants. Moreover, the constant presence of chondroid tissue, related with the mechanical induction by forces applied on the recovering area, strongly suggests that the mechanisms implied in osteointegration are related to endomembranous, rather than endochondral ossification processes

BS-SEM evaluation of the tisular interactions between cortical bone and calcium-phosphate covered titanium implants

The improvement of the reliability of the contact between the osseous tissues and the implant materials has been tested by recovering the metallic implants with ceramic materials, usually calcium phosphates. In our study, the calcium phosphate recovering layers were deposited by means of a pulsed-laser deposition technique. Our aim was to to evaluate the tissue interactions established between cortical bone and titanium implants covered by five different layers, ranging from amorphous calcium phosphate to crystalline hydroxyapatite, obtained by altering the parameters of the laser ablation process. The surgical protocol of the study consisted in the simultaneous implantation of the five types of implants in both the tibial dyaphisis of three Beagle dogs, sacrificed respectively one, two and three months after the last surgical procedures. After the sacrifice, the samples were submitted to a scheduled procedure of embedding in plastic polymers without prior decalcification, in order to perform the ultrastructural studies: scanning microscopy with secondary and backscattered electrons (BS-SEM). Our observations show that both in terms of the calcified tissues appearing as a response to the presence of the different coatings and of time of recovering, the implants coated with crystalline calcium phosphate layers by laser ablation present a better result than the amorphous-calcium-phosphate-coated implants. Moreover, the constant presence of chondroid tissue, related with the mechanical induction by forces applied on the recovering area, strongly suggests that the mechanisms implied in osteointegration are related to endomembranous, rather than endochondral ossification processes

BS-SEM evaluation of the tisular interactions between cortical bone and calcium-phosphate covered titanium implants

The improvement of the reliability of the contact between the osseous tissues and the implant materials has been tested by recovering the metallic implants with ceramic materials, usually calcium phosphates. In our study, the calcium phosphate recovering layers were deposited by means of a pulsed-laser deposition technique. Our aim was to to evaluate the tissue interactions established between cortical bone and titanium implants covered by five different layers, ranging from amorphous calcium phosphate to crystalline hydroxyapatite, obtained by altering the parameters of the laser ablation process. The surgical protocol of the study consisted in the simultaneous implantation of the five types of implants in both the tibial dyaphisis of three Beagle dogs, sacrificed respectively one, two and three months after the last surgical procedures. After the sacrifice, the samples were submitted to a scheduled procedure of embedding in plastic polymers without prior decalcification, in order to perform the ultrastructural studies: scanning microscopy with secondary and backscattered electrons (BS-SEM). Our observations show that both in terms of the calcified tissues appearing as a response to the presence of the different coatings and of time of recovering, the implants coated with crystalline calcium phosphate layers by laser ablation present a better result than the amorphous-calcium-phosphate-coated implants. Moreover, the constant presence of chondroid tissue, related with the mechanical induction by forces applied on the recovering area, strongly suggests that the mechanisms implied in osteointegration are related to endomembranous, rather than endochondral ossification processes

A comparison of the dental status and treatment needs of older adults with and without chronic mental illness in Sevilla, Spain

Objectives: To study the dental status and treatment needs of institutionalized older adults with chronic mental illness compared to a non-psychiatric control sample. Study Design: The sample size was 100, in which 50 were psychogeriatric patients (study group; SG) classified according to DSM-IV, with a mean age of 69.6 ± 6.7 years, and 50 non-psychiatric patients (control group; CG), with a mean age of 68.3 ± 6.9 years. Clinical oral health examinations were conducted and caries were recorded clinically using the Decayed, Missing and Filled Teeth Index (DMFT). Results were analyzed statistically using the Student"s t-test or analysis of variance. Results: Caries prevalence was 58% and 62% in SG and CG, respectively. DMFT index was 28.3 ± 6.6 in SG and 21.4 ± 6.07 in CG (p < 0.01). Mean number of decayed teeth was higher in SG (3.1) compared to CG (1.8) (p=0.047). Mean number of missing teeth were 25.2 and 16.4 in SG and CG respectively (p<0.05). DMFT scores were higher in SG in all the age groups (p < 0.01). Mean number of teeth per person needing treatment was 3.4 in SG and 1.9 in CG (p= 0.037). The need for restorative dental care was significantly lower in the SG (0.8 teeth per person) than in the CG (1.7 teeth per person) (p = 0.043). Conclusions: Institutionalized psychiatric patients have significantly worse dental status and more dental treatment needs than non-psychiatric patients.

Rehabilitation of atrophic maxilla: a review of 101 zygomatic implants

Introduction: Zygomatic implants are a good rehabilitation alternative for upper maxilla with severe bone reabsorption. These implants reduce the need for onlay-type bone grafting in the posterior sectors and for maxillary sinus lift procedures - limiting the use of bone grafts to the anterior zone of the upper jaw in those cases where grafting is considered necessary. Objective: To evaluate the survival of 101 zygomatic implants placed in upper maxilla presenting important bone reabsorption, with a follow-up of 1-72 months. Patients and methods: A retrospective study was made of 101 Zygoma® implants (Nobel Biocare, Göteborg, Sweden) placed in 54 patients with totally edentulous and atrophic upper maxilla, in the period between 1998-2004. There were 35 women and 19 men, subjected to rehabilitation in the form of fixed prostheses and overdentures using 1-2 zygomatic implants and 2-7 implants in the anterior maxillary zone. The principal study variables were smoking, a history of sinusitis, the degree of bone reabsorption, and peri-implant bone loss, among others. Results: The descriptive analysis of the 101 zygomatic implants placed in 54 patients with a mean age of 56 years (range 38-75) yielded a percentage survival of 96.04%, with four failed implants that were removed (two before and two after prosthetic loading). Nine patients were smokers, and none of the 54 subjects reported a history of sinus disorders. Discussion and conclusions: Zygomatic implants are designed for use in compromised upper maxilla. They allow the clinician to shorten the treatment time, affording an interesting alternative for fixed prosthetic rehabilitation. This study confirms that zygomatic bone offers predictable anchorage and acceptable support function for prostheses in atrophic jaws. However, these implants are not without complications. Longer-term evaluations are needed of zygomatic implant survival in order to establish a correct clinical prognosis

Relationship between oral cancer and implants: clinical cases and systematic literature review

The use of implants for oral rehabilitation of edentulous spaces has recently been on the increase, which has also led to an increase in complications such as peri-implant inflammation or peri-implantitis. Chronic inflammation is a risk factor for developing oral squamous cell carcinoma (OSCC). Objectives: To review the literature of cases that associate implant placement with the development of oral cancer. Study design: We present two clinical cases and a systematic review of literature published on the relationship between oral cancer and implants. Results: We found 13 articles published between the years 1996 and 2009, referencing 18 cases in which the osseointegrated implants are associated with oral squamous cell carcinoma. Of those, 6 articles were excluded because they did not meet the inclusion criteria. Of the 18 cases reported, only 7 cases did not present a previous history of oral cancer or cancer in other parts of the body. Conclusions: Based on the review of these cases, a clear cause-effect relationship cannot be established, although it can be deduced that there is a possibility that implant treatment may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of OSCC.

Thermal increment due to ErCr: YSGG and CO2 laser irradiation of different implant surfaces. A pilot study

Objective: An evaluation and comparison is made of the thermal increment at different implant surfaces during irradiation with CO2 and ErCr:YSGG lasers. Study design: Five threaded and impacted implants with four types of surfaces were inserted in an adult pig rib: two implants with a hydroxyapatite surface (HA)(impacted and threaded, respectively), a machined titanium surface implant (TI mach), a titanium plasma spray surface implant (TPS), and a sandblasted, acid-etched surface implant (SBAE). A 0.5-mm diameter bone defect was made in the implant apical zone, and a type-K thermocouple (Termopar)® was placed in contact with the implant. The implants were irradiated in the coronal zone of each implant with a CO2 (4 W continuous mode) and an ErCr:YSGG laser (1.5 W, pulsed mode) first without and then with refrigeration. The temperature variations at the implant apical surface were recorded. Results: An apical temperature increase was recorded in all cases during CO2 and ErCr:YSGG laser irradiation without refrigeration. However, when the ErCr:YSGG was used with a water spray, a decrease in temperature was observed in all implants. The acid-etched and sandblasted surfaces were those most affected by the thermal changes. Conclusions: The ErCr:YSGG laser with a water spray applied to the sealing cap or coronal zone of the implants does not generate thermal increments in the apical surface capable of adversely affecting osseointegration and the integrity of the peri-implant bone tissue

Traumatic bone cyst: a retrospective study of 21 cases

Objective: To describe the clinical and radiological characteristics, and surgical findings of traumatic bone cysts. Study Design: A retrospective observational study was made of 21 traumatic bone cysts. The diagnosis was based on the anamnesis, clinical examination, and complementary tests. Panoramic and periapical X-rays were obtained in all cases, together with computed tomography as decided by the surgeon. A descriptive statistical analysis was made of the study variables using the SPSS v12.0 for Windows. Results: There was a clear female predominance (14:7). The mean age was 26.5 years (range 8-45 years). The cysts in all cases constituted casual findings during routine radiological exploration. In those cases where computed tomographic images were available, preservation of the vestibular and lingual cortical layers was observed. Five of the 21 patients (23.8%) reported a clear antecedent of traumatism in the affected zone. All the lesions were subjected to surgery, and the cavities were found to be vacant in 90.5% of the cases. In only two patients were vascular contents seen within the cavity. Two of the patients presented postoperative paresthesia of the inferior dental nerve that subsided within two weeks. The 19 patients in whom adequate postoperative follow-up proved possible all showed complete bone healing. Conclusions: Traumatic bone cysts were a casual finding. During the surgery, most cases showed to be vacant cavity without an ephitelial lining. Careful curettage of the lesion favors progressive bone regeneration, offering a good prognosis and an almost negligible relapse rate. Other treatment options only would be justified in cases of relapse.

Graft materials in oral surgery: revision

Oral implantology is a common procedure in dentistry, especially for fully or partially edentulous patients. The implants must be placed in the best location from both the aesthetic and functional point of view. Because of this it is increasingly more frequent to resort to regeneration techniques that use substitutes of the bone itself, in order to be able to insert the implants in the most appropriate location. Material and Methodology: A review was performed on the literature from the last ten years based on the following search limitations: "graft materials', 'allograft', 'xenograft', 'autologous graft" and 'dentistry". Results: 241 works were obtained that after reading their respective summaries, they were reduced to 38, and 9 previous works were included in order to summarize the concepts. Discussion: Autologous grafts are the 'gold standard' of the bone regeneration. They have obvious advantages, but they also have drawbacks. This is why allogeneic and xenogeneic tissues are used. The former because of their clear similarity with the recipient's tissue and the latter due to their wide availability. Given that these grafts also have drawbacks, the industry has developed synthetic materials that have properties similar to those of human bone tissue. However, as of today, the ideal material to substitute human bone has not yet been found. In recent years the tendency has been to combine these synthetic materials with the patient's own bone, which is extracted during drilling in implant placement, with bone marrow aspiration, or with bone morphogenetic proteins. Thus the intention is to equip these substances with the osteogenic capacity. Conclusions: There is currently no ideal graft material, with the exception of those materials that come directly from the patient. We hope that in the coming years we will have products that will allow us to perform rehabilitations with better results and provide a better quality of life for our patients, especially those who have more complex situations to resolve, like the patients that are operated on for head and neck cancer