RESUMO
The globally increasing incidence of cancer, including melanoma, requires novel therapeutic strategies. Development of successful novel drugs is based on clear identification of the target mechanisms responsible for the disease progression. The specific cancer microenvironment represents a critically important aspect of cancer biology, which cannot be properly studied in simplistic cell culture conditions. Among other traditional options, the study of melanoma cell growth on the chicken chorioallantoic membrane offers several significant advantages. This model offers increased complexity compared to usual in silico culture models and still remains financially affordable. Using this model, we studied the growth of three established human melanoma cell lines: A2058, BLM, G361. The combination of histology, immunohistochemistry with the application of human-specific antibodies, intravascular injection of contrast material such as filtered Indian ink, Mercox solution and phosphotungstic acid, and X-ray micro-CT and live-cell monitoring was employed. Melanoma cells spread well on the chicken chorioallantoic membrane. However, invasion into the stroma of the chorioallantoic membrane and the limb primordium graft was rare. The melanoma cells also significantly influenced the architecture of the blood vessel network, resulting in the orientation of the vessels to the site of the tumour cell inoculation. The system of melanoma cell culture on the chorioallantoic membrane is suitable for the study of melanoma cell growth, particularly of rearrangement of the host vascular pattern after cancer cell implantation. The system also has promising potential for further development.
Assuntos
Membrana Corioalantoide/metabolismo , Melanoma Experimental/metabolismo , Modelos Biológicos , Animais , Embrião de Galinha , Galinhas , Membrana Corioalantoide/patologia , Humanos , Imuno-Histoquímica , Melanoma Experimental/patologia , Células Tumorais CultivadasRESUMO
BACKGROUND: The contemporary approach of dentistry towards interdisciplinary cooperation is based on the neuromuscular concept. In recent years many authors have pointed out a correlation between orthopaedic and dental findings. Furthermore, there is an intimate biomechanical interrelationship of occlusion with cerebral fluid circulation, left and right equilibrium, gaze stabilisation and headache. The influence of a dental occlusion and temporomandibular joint (TMJ) status on general health has been widely analysed in the current scientific literature. AIM: The aim of this analytic study was to display the deep relationship between dentistry and other fields of medicine, and to show the necessity of wide cooperation between dentists and physicians. CONCLUSIONS: This study was based on a review of 41 sources, including specialised articles and books. The significance of different anatomical and physiological preconditions (occlusion, muscles and TMJ status) was considered and evaluated separately. However, as a result of modern concepts of general body health, extending cooperation between different fields of medicine is essential. The practical application of the principles of neuromuscular dentistry enables one to increase greatly the treatment efficiency of aches in muscles, headaches, postural dysfunctions as well as of many other diseases. However, the dentist's contribution to the development of an interdisciplinary approach is underestimated. Many theoretical aspects of the interdisciplinary relationship have not been sufficiently examined, hence the practical consequences remain unclear. Further research in the field is urgently needed.
Assuntos
Oclusão Dentária , Junção Neuromuscular/fisiologia , Sistema Estomatognático/fisiologia , Odontólogos , Humanos , Relações Interprofissionais , Músculo Esquelético/fisiologia , Médicos , Postura/fisiologia , Doenças Estomatognáticas/terapia , Sistema Estomatognático/inervação , Articulação Temporomandibular/fisiologiaRESUMO
The objective of this study was to create a real model of a face using the well preserved "Bochdalek's skull" (from an eighteenth Century female aged 18 years) kept in the museum of anatomy (Institute of Anatomy, 1st Medical Faculty, Charles University in Prague). The skull had previously been appraised as a deformed skull with an adhesion present on both sides of the jaw, most likely of post-traumatic origin (bilateral syngnathia). In an attempt to find the best description for it, and to identify the spatial relationships between the surface of the facial bones which had changed in shape, as well as the formation of soft tissue on the face, we decided to perform a 3D reconstruction of the face. Due to the necessity of preserving the unique original undamaged skull, we created an exact digital "casting" of the facial bone structure on a computer first, which we then converted into a three-dimensional model using a 3D RepRap printer. We needed to take into consideration the fact that we had no portrait of the girl, just the skull. For this reason, we opted for a selected combination of anthropologic steps (the modified Manchester technique), which in our view, allows for optimum creation of the topography of the face in keeping with the deformed skull. The resulting reconstructed face was old in appearance with an overhanging lower lip and flattened surfaces in the areas of the temporalis and masseter muscles.
Assuntos
Simulação por Computador , Face/anatomia & histologia , Imageamento Tridimensional , Mandíbula/anormalidades , Maxila/anormalidades , Feminino , Antropologia Forense/métodos , História do Século XVIII , HumanosRESUMO
The aim of this work was to document and analyze an exceptionally preserved mummified body of a six-year-old boy found in a family tomb in Skalná, Czech Republic. The boy died of scarlet fever in 1887, and was buried under ground in a cemetery in an unknown coffin shortly after death. His parents exhumed his cadaver and entombed it in the family crypt in two tin coffins a year later. This secondary burial and violent opening of the coffins in the end of the World War II leaving the body exposed to external climatic conditions led to its natural (spontaneous) dry mummification. The computed tomography scan of the corpse showed that the majority of internal organs were well preserved. And surprisingly, parts of the central nervous system estimated to be about 70% of the original size with distinguishable neural structures. We tested the cerebellum, tentorium and hair for mercury and arsenic, and the body was assessed by a forensic examiner for possible signs of an artificial embalming, and pathology. We did not confirm the hypothesis of the eventual preservation using the salts of mercury and/or arsenic or other fixation common for embalming in the 1800s. The anthropogenic mummification can be excluded due to the presence of fly larvae, historical records confirmed the burial of the individual right after death, and the different degree of organs condition. It appears that the unique preservation of the mummy and its internal organs was most likely caused by stable conditions of the environment.
RESUMO
Current models of the vocal folds derive their shape from approximate information rather than from exactly measured data. The objective of this study was to obtain detailed measurements on the geometry of human vocal folds and the glottal channel in phonatory position. A non-destructive casting methodology was developed to capture the vocal fold shape from excised human larynges on both medial and superior surfaces. Two female larynges, each in two different phonatory configurations corresponding to low and high fundamental frequency of the vocal fold vibrations, were measured. A coordinate measuring machine was used to digitize the casts yielding 3D computer models of the vocal fold shape. The coronal sections were located in the models, extracted and fitted by piecewise-defined cubic functions allowing a mathematical expression of the 2D shape of the glottal channel. Left-right differences between the cross-sectional shapes of the vocal folds were found in both the larynges.
Assuntos
Glote/anatomia & histologia , Modelos Biológicos , Prega Vocal/anatomia & histologia , Voz/fisiologia , Idoso , Fenômenos Biomecânicos/métodos , Feminino , Glote/fisiologia , Humanos , Imageamento Tridimensional/estatística & dados numéricos , Masculino , Prega Vocal/fisiologiaRESUMO
BACKGROUND: Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy. OBJECTIVE: Since talin is involved in transmembrane connections between extracellular matrix and cytoskeleton, this study investigates the subcellular pattern of talin immunoreactivity and the effect of NGF treatment of diabetic rats on the distribution of talin in the sciatic nerve. MATERIALS AND METHODS: Post-embedding immunogold electron microscopy using monoclonal antibody against talin in combination with quantitative procedures was employed to localize talin-like immunoreactivity in the sciatic nerve of normal, diabetic and NGF treated diabetic rats. RESULTS: We found the highest densities of gold particles in the Schwann cells (139.6+/-5.6 particles/microm2) and in the fibroblasts (127.4+/-4.1 particles/microm2). A moderate amount of immunoreactivity was also present in the endothelial cells of vasa nervosa (32.3+/-9.1 particles/microm2). The myelinated and unmyelinated nerve fibers and the extracellular matrix profiles were not labeled (8.7+/-2.1 particles/microm2, 4.2+/-2.2 particles/microm2, 6.1+/-3.2 particles/microm2, 9.5+/-5.3 particles/microm2, respectively). The immunogold localization of talin in diabetic rats was significantly (p<0.001) reduced in Schwann cells (66.3+/-6.5 particles/microm2) and perineurial and epineurial fibroblasts (56.8+/-3.9 particles/microm2). Diabetic rats treated with NGF for 12 weeks showed significant (p<0.005) increase in talin-like immunogold density in Schwann cells and fibroblasts. Talin immunogold density in Schwann cells and fibroblasts increased approximately 68% and 58%, respectively, after NGF treatment. The endothelial cells of endoneurial and epineurial vessel walls showed no significant change in the talin-like immunogold particle density among control, diabetic and NGF treated diabetic animals. CONCLUSIONS: These results have shown that the administration of exogenous NGF may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy through maintaining the permeability of the barrier properties of the peripheral nerve.
Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas/metabolismo , Fator de Crescimento Neural/fisiologia , Nervo Isquiático/metabolismo , Talina/metabolismo , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Fibroblastos/metabolismo , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Fator de Crescimento Neural/administração & dosagem , Fator de Crescimento Neural/farmacologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Nervo Isquiático/fisiologia , Estreptozocina , Talina/análise , Fatores de TempoRESUMO
OBJECTIVES: To distinguish the layers of the vocal fold at the submacroscopic level and determine their boundaries, thereby creating a basis for the construction of a digital 3D model of the human vocal folds. STUDY DESIGN: The submacroscopic delineation of individual layers of fixed vocal ligaments based on their structural differences. METHODS: Following tasks were performed: (1) Submicroscopic dissection of the vocal folds fixed in a solution with a low concentration of fixation substance (in this case, the muscular parts of the vocal folds were removed); (2) Using the CT and micro-MRI methods, we determined the position of the dense parts of the vocal folds; and (3) Using a modified plastination method, we preserved macroscopically natural appearance of all ligamentous and muscular layers. RESULTS: The vocal ligament is composed of several volumes of connective tissue. It is surrounded by layers of fibrous material permeated by liquid. Individual fibers stretch all the way to the fibrous casing (fascia) of the vocal muscle. The vocal fold layer surrounding the ligament externally has a stratified character. CONCLUSIONS: According to our findings, we infer that this ligament is a complex of several fibrous bundles which are surrounded by a thin layer of connective tissue. Below the surface of epithelium of the vocal fold run several separate bands which are closely adjacent to it. Therefore, we propose using the term ligamentous complex involving closely adjacent structures, instead of the vocal ligament only. We feel that it better reflects the functional and structural character of the whole formation.
Assuntos
Gráficos por Computador , Simulação por Computador , Glote/anatomia & histologia , Imageamento Tridimensional , Modelos Anatômicos , Prega Vocal/anatomia & histologia , Idoso , Dissecação , Feminino , Glote/diagnóstico por imagem , Glote/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fonação , Tomografia Computadorizada por Raios X , Prega Vocal/diagnóstico por imagem , Prega Vocal/fisiologia , Prega Vocal/cirurgia , VozRESUMO
The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells.
Assuntos
Imunoterapia/métodos , Imunoterapia/tendências , Melanoma/terapia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Humanos , Melanoma/etiologia , Melanoma/imunologia , Metanálise como AssuntoRESUMO
We investigated the effect of green tea (GT) in unilateral chronic constriction injury (CCI) to the rat scaitic nerve. Five groups (n = 6 rats/group) sham group: rats which underwent operation but with no ligation to the scaitic nerve, and received tap water for two weeks before and for five weeks after the surgery. Four experimental groups underwent CCI to the right sciatic nerve, divided randomly as follows: group E were given tap water throughout the study. Group B received GT before and after CCI. Group C was given GT following CCI. Group D received GT for two weeks prior to CCI. Groups which consumed GT showed significant improvement in the toe spread (P < 0.001) and foot positioning (P < 0.001) tests compared to the experimental control group. In addition, these groups showed a significant decrease in the behavioral mechanical hyperalgesia (P < 0.0001) and allodynia (P < 0.0002). Consumption of GT improves both reflexes and sensation which are often affected in the course of peripheral neuropathy.
Assuntos
Analgesia , Neuropatia Ciática/fisiopatologia , Chá , Animais , Constrição , Modelos Animais de Doenças , Pé , Masculino , Atividade Motora , Medição da Dor , Pressão , Ratos , Ratos Sprague-Dawley , Reflexo , Nervo Isquiático/lesões , Sensação , Dedos do PéRESUMO
Liposomal meso-tetrakis-phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg x kg(-1)) followed by PDT lamp irradiation (600-700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post-PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i.v.) administered liposomal (3.2 mg x kg(-1)) TPP mostly disintegrated tumours to zero volumes. Melanoma remissions were accompanied by tumour surface necroses and were documented by the appearance of nontumourous cells with nonpycnotic nuclei. Spatial arrangement of capillaries in remissing tumour was the same as in healthy surrounding tissue. Lower TPP doses (1, 0.3 and 0.1 mg x kg(-1)) were more or equally efficient than hydrophilic TPPS(4) (3.2 mg x kg(-1), i.e., sulfonated TPP), i.v. administered also in liposomes. Liposomal TPPS(4) only delayed the onset of subsequent tumour growth. Commercial Photosan 3 disintegrated tumours only in doses of approx. 7.5 mg x kg(-1); in lower doses it was less efficient than TPPS(4). The second PDT cycle (3.2 mg x kg(-1) TPP or 7.5 mg x kg(-1) Photosan 3), performed in a few unsuccessfully cured mice, predominantly led again to tumour remissions. Since the measured TPP and TPPS(4) content in melanomas was similar, these results demonstrate the advantage of PDT with a hydrophobic photosensitizer such as TPP. Photophysical properties of TPP and TPPS(4) are equal, but TPP has probably more favorable intracellular distribution, as documented by our studies, which leads to more efficient PDT. Consequently, liposomal TPP is suggested as a potentially suitable efficient preparation for PDT.