Orientador: Alvimar Lima de Castro / Banca: Renata Tucci / Banca: José Fernando Garcia / Banca: Sérgio Roberto Peres Line / Banca: José Américo de Oliveira / Resumo: INTRODUÇÃO: As alterações em gengiva induzidas por medicamentos têm sido pouco estudadas quanto à expressão in vivo dos genes das metoloproteinases (MMPs). O objetivo do presente trabalho foi avaliar o padrão histológico de distribuição de fibras colágenas após a administração de ciclosporina, nifedipina ou fenitoína e correlacionar com a expressão dos genes do colágeno do tipo I, MMP-1 e MMP2. MATERIAL E MÉTODO: Amostras da gengiva da área de canino superior direito foram obtidas de doze macacos prego (Cebus apella) machos. A extremidade mesial de cada amostra foi imediatamente congelada em nitrogênio líquido enquanto que a distal foi processada para inclusão em parafina. Após uma semana, os animais foram divididos em três grupos que receberam doses diárias de ciclosporina, fenitoína ou nifedipina, durante 120 dias. Procedeu-se à remoção de amostras da gengiva da área do canino superior esquerdo de dois animais de cada grupo aos 52 e 120 dias. Os cortes histológicos foram corados pelas técnicas da hematoxilina e eosina, vermelho picrosirius, além da marcação imunoistoquímica para colágeno do tipo IV. O RT-PCR semiquantitativo foi realizado para se determinar os níveis de mRNA. RESULTADOS: No grupo controle, houve o predomínio de fibras colágenas maduras, evidenciadas com a cor vermelha em cortes corados pela técnica do vermelho picrosirius analisados com microscópio de luz polarizada. Observou-se nos grupos tratados aos 52 e 120 dias um aumento da porcentagem de áreas ocupadas por fibras imaturas, em todos os grupos, independentemente da idade do animal. No entanto, não foram observadas diferenças morfológicas entre os grupos controle e tratado nos cortes corados pela hematoxilina e eosina. Houve uma tendência a valores médios mais baixos ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Few studies have focused on the in vivo expression of matrix metalloproteinase (MMP) genes in gingival changes induced by drugs. The aim of the present study was to evaluate the histological pattern of collagen fiber distribution after phenytoin, cyclosporine or nifedipine medication and correlate with collagen type 1, MMP-1 and MMP-2 gene expression levels. Methods: Gingival samples were obtained from superior right canine area of twelve male capuchin monkeys (Cebus apella). The mesial part of the biopsy specimens was immediately frozen in liquid nitrogen, while the distal one was processed for paraffin inclusion. One week after the control biopsy, the animals were divided in three groups that received daily doses of cyclosporine, phenytoin or nifedipine during 120 days. Gingival samples were obtained from left superior canine area on 52nd and 120th day of treatment (two animal of each experimental group). Histologic sections were subjected to hematoxylin and eosin, picrosirius red stainings, and to immunohistochemical reaction for collagen type IV. MMP-1, MMP-2 and collagen type I mRNA levels were determined by RT-PCR. Results: Predominance of mature collagen fibers was observed in the control group after picrosirius red staining, visualized as red fibers under polarized microscope. Increased percentage of areas occupied by immature collagen fibers was observed on 52 and 120 experimental periods, in all groups, despite the animal age. However, no morphological differences between treated and control groups were observed on hematoxilin and eosin stained sections. There was a trend to lower levels of MMP-1 expression on 52-day samples. However, MMP-2 and collagen type I gene expressions seemed to be phased and drug-related. Conclusions: The results allowed the ...(Complete abstract click electronic access below) / Doutor

A heterogeneidade da linha média observada nas pacientes submetidas à dermolipectomia abdominal e os inúmeros estudos demonstrando a importância do colágeno na estrutura e força tênsil das aponeuroses, suscitaram o interesse em conhecer o índice dos colágenos tipo I e III da linha média. O objetivo deste trabalho é avaliar a quantidade dos colágenos tipo I e III de mulheres com e sem diástase de músculos retos do abdome, assim como identificar se existe diferença na proporção entre colágeno I e III nas aponeuroses da linha média entre os dois grupos. Métodos: Trata-se de um estudo de caso-controle aninhado a uma coorte incluindo 18 pacientes do sexo feminino com diástase de músculos retos do abdome e um grupo controle de 18 pacientes de mesmo gênero sem apresentar essa condição. Foram coletadas amostras da linha média 3cm acima e 2cm abaixo da cicatriz umbilical. As amostras foram submetidas a análise imuno-histoquímica utilizando anticorpos policlonais anticolágeno tipos I e III. Resultados: Nas mulheres com diástase de músculos retos do abdome, as quantidades de colágeno tipo I e III são menores de que naquelas sem essa condição, tanto nas amostras de aponeurose da linha alba obtidas acima da cicatriz umbilical quanto abaixo da mesma (P<0,001). A proporção entre colágeno tipos I e III é menor nas mulheres com diástase de músculos retos do abdome nas amostras de aponeurose obtidas acima da cicatriz umbilical (P<0,001), não havendo diferença estatisticamente significativa entre os grupos com e sem diástase (P = 0,110) nas amostras obtidas abaixo da cicatriz umbilical. Conclusões: As menores quantidades de colágeno tipos I e III encontrados na aponeurose da linha média podem ser considerados importante fator na diástase dos músculos retos do abdome. / Differences observed in the midline of the abdominal wall in patients undergoing abdominoplasty and evidence from a number of studies showing the importance of collagen to aponeurotic structures and tensile strength have raised interest in investigating the rates of type I and type III collagen in this anatomic region. The aim of this study was to assess the amount of type I and type III collagen in the linea alba of women with and without diastasis recti and to determine collagen type I/III ratio by comparing these two groups. This is a case-control study nested within a surgical cohort of 18women with diastasis recti and a control group with 18 women without diastasis recti. Samples were collected from de midline of the abdominal wall three centimeters above and two centimeters bellow the umbilical scar. The samples were analyzed by immunohistochemistry using polyclonal antibodies to collagen type I and type III. The amount of collagen type I and type III was smaller in women with diastasis recti than in those without this condition in samples collected from the linea alba above and bellow the umbilical scar (P<0,001). Collagen type I/III ratio was lower in womem with diastasis recti in the samples collected above de umbilical scar (P<0,001). However, there was no statistically significant difference between groups with and without distasis recti in the samples collected bellow de umbilical scar (P = 0,110). The lower amount of collagen type I and III observed in the midline of the abdominal wall could be a factor in diastasis recti.

A matriz extracelular apresenta importante papel na fisiologia da fonação sendo necessário o conhecimento de seus componentes. Poucos estudos sobre os componentes da matriz em fetos e a ausência de relatos do versican nesta faixa etária, bem como a necessidade de aprofundar os conhecimentos sobre os componentes da matriz em adultos, resultaram na elaboração deste estudo. Analisar a presença e distribuição do colágeno tipo I, colágeno tipo III e proteoglicano versican na lâmina própria da prega vocal de laringes fetais e adultas é o objetivo do estudo. No grupo fetal foram estudadas 7 laringes obtidas de cadáveres variando de 28 a 36 semanas de idade gestacional. No grupo adulto foram estudadas 20 laringes, 10 do sexo masculino, com média de idade de 66 anos, e 10 do sexo feminino com média de idade de 70 anos, com idades pareadas. Utilizou-se método imunoistoquímico para avaliar a expressão do versican no grupo fetal e adulto. Para a avaliação das fibras colágenas utilizou-se o método da Picrosirius polarização no grupo fetal e imunoistoquímico no grupo adulto. A quantificação das fibras colágenas e do versican foi realizada por meio de análise digital de imagens. Os resultados do grupo fetal mostraram uma distribuição homogênea das fibras colágenas formando uma estrutura monolaminar com um entrelaçamento entre as fibras denominado arranjo em cesta de vime; em relação ao versican, este apresentou uma densidade maior na camada superficial e intermediária da lâmina própria. Os resultados do grupo adulto mostraram uma menor densidade de colágeno tipo I na camada intermediária quando comparado à camada superficial (p<0.001) e camada profunda (p=0.005). O colágeno tipo III apresentou distribuição mais homogênea nas camadas da lâmina própria, com uma densidade estatisticamente menor na camada intermediária quando comparada à camada profunda (p=0.001), mas sem diferença estatística na camada superficial. O versican apresentou densidade menor na camada superficial quando comparado à camada intermediária (p=0.036) e camada profunda (p=0.013). Houve menor densidade de versican nas mulheres quando comparado aos homens, percebida apenas na camada superficial. Quando todas as camadas foram consideradas conjuntamente houve uma correlação positiva entre a densidade de versican e colágeno tipo III (r=0.57; p=0.010). Este estudo mostrou as diferenças na distribuição dos componentes da matriz nas camadas da lâmina própria em dois grupos etários proporcionando uma discussão sobre as implicações destes achados na fisiologia vocal e sugerindo que as estruturas glóticas já estariam preparadas para a vocalização ao nascimento / Extracellular matrix has an important rule in the vocal fold physiology and the knowledge about your components is necessary. Fewer studies about matrix extracellular and no studies about versican in fetuses, and the necessity to improve the knowledge about extracellular matrix components in adults group came us to the elaboration of this study that has the objective to analyze the presence and distribution of collagen type I, type III and versican in human vocal fold lamina propria of fetal and adult larynges. Seven fetal larynges obtained from 28- to 36- week-old cadaveric fetuses were studied. Twenty larynges were obtained from adults (10 males and 10 females). Mean age of males was 66 and 70 from females, without significant statistical difference between groups. For the analysis of versican expression, immunohistochemical reactions were carried out in fetal and adult group. The larynges were analyzed through Picrosirius polarization method and immunohistochemistry to visualize the collagen fibers, in fetal and adult group respectively. Collagen fibers and proteoglycan were quantified using a digital image analysis system. In fetuses, the collagen fibers system exhibited homogeneous distribution pattern in a monolaminar layer and spatial arrangement as in a wicker basket; predominance of versican distribution was found out on the superficial and intermediate layer of vocal fold lamina propria. In adult group, there was a lower collagen type I density in the intermediate layer when compared to the superficial (p<0.001) and the deep layers (p=0.005). Collagen type III presented a lower density in the intermediate layer when compared to the deep layer (p=0.001) but without differences in the superficial layer. There was a lower versican density in the superficial layer when compared to the intermediate layer (p=0.036) and deep layer (p=0.013). There was a lower versican density in the lamina propria of females when compared with males. The difference was noted in the superficial layer only. When all layers are considered together there was a positive correlation between versican and collagen type III densities (r=0.57; p=0.010). This study shows the differences in the extracellular matrix components distribution in lamina propria vocal folds in fetal and adult group permitting a discussion about the implications in vocal fold physiology and suggesting that laryngeal structures will be prepared to vocalization at birth

A heterogeneidade da linha média observada nas pacientes submetidas à dermolipectomia abdominal e os inúmeros estudos demonstrando a importância do colágeno na estrutura e força tênsil das aponeuroses, suscitaram o interesse em conhecer o índice dos colágenos tipo I e III da linha média. O objetivo deste trabalho é avaliar a quantidade dos colágenos tipo I e III de mulheres com e sem diástase de músculos retos do abdome, assim como identificar se existe diferença na proporção entre colágeno I e III nas aponeuroses da linha média entre os dois grupos. Métodos: Trata-se de um estudo de caso-controle aninhado a uma coorte incluindo 18 pacientes do sexo feminino com diástase de músculos retos do abdome e um grupo controle de 18 pacientes de mesmo gênero sem apresentar essa condição. Foram coletadas amostras da linha média 3cm acima e 2cm abaixo da cicatriz umbilical. As amostras foram submetidas a análise imuno-histoquímica utilizando anticorpos policlonais anticolágeno tipos I e III. Resultados: Nas mulheres com diástase de músculos retos do abdome, as quantidades de colágeno tipo I e III são menores de que naquelas sem essa condição, tanto nas amostras de aponeurose da linha alba obtidas acima da cicatriz umbilical quanto abaixo da mesma (P<0,001). A proporção entre colágeno tipos I e III é menor nas mulheres com diástase de músculos retos do abdome nas amostras de aponeurose obtidas acima da cicatriz umbilical (P<0,001), não havendo diferença estatisticamente significativa entre os grupos com e sem diástase (P = 0,110) nas amostras obtidas abaixo da cicatriz umbilical. Conclusões: As menores quantidades de colágeno tipos I e III encontrados na aponeurose da linha média podem ser considerados importante fator na diástase dos músculos retos do abdome. / Differences observed in the midline of the abdominal wall in patients undergoing abdominoplasty and evidence from a number of studies showing the importance of collagen to aponeurotic structures and tensile strength have raised interest in investigating the rates of type I and type III collagen in this anatomic region. The aim of this study was to assess the amount of type I and type III collagen in the linea alba of women with and without diastasis recti and to determine collagen type I/III ratio by comparing these two groups. This is a case-control study nested within a surgical cohort of 18women with diastasis recti and a control group with 18 women without diastasis recti. Samples were collected from de midline of the abdominal wall three centimeters above and two centimeters bellow the umbilical scar. The samples were analyzed by immunohistochemistry using polyclonal antibodies to collagen type I and type III. The amount of collagen type I and type III was smaller in women with diastasis recti than in those without this condition in samples collected from the linea alba above and bellow the umbilical scar (P<0,001). Collagen type I/III ratio was lower in womem with diastasis recti in the samples collected above de umbilical scar (P<0,001). However, there was no statistically significant difference between groups with and without distasis recti in the samples collected bellow de umbilical scar (P = 0,110). The lower amount of collagen type I and III observed in the midline of the abdominal wall could be a factor in diastasis recti.

O objetivo deste estudo foi avaliar e comparar a reparação tecidual após incisões com os lasers de CO2 e de diodo, bisturi elétrico e convencional em língua e pele de 30 ratos Wistar. Incisões de 5 mm de comprimento por 2 mm de profundidade na pele, e de 2,5 mm de comprimento por 1 mm de profundidade na língua, foram feitas nestes tecidos, e os animais sacrificados nos intervalos de zero, 24, 48, 72 horas, 7 e 14 dias após as intervenções. Cortes histológicos foram obtidos das incisões e submetidos a 3 tipos de análises: quantificação do dano tecidual, de mastócitos e da densidade de colágeno tipo I. Os dados foram submetidos à análise estatística pelo teste ANOVA de Kruskal-Wallis e pelo teste de comparações múltiplas de Turkey-Kramer, com nível de significância estabelecida para P < 0,05. Os resultados mostraram que o dano tecidual na pele das incisões realizadas com lasers e bisturi elétrico foi significativamente maior do que o do bisturi convencional (P < 0,05). Quanto às incisões na língua, houve diferença significante de menor dano tecidual resultante da incisão do bisturi convencional comparado com o das incisões realizadas com laser de CO2 2 W, laser de diodo 4 W e bisturi elétrico (P < 0,05). A quantificação de mastócitos mostrou diferenças estatísticas entre as incisões realizadas com bisturi convencional em relação às outras incisões (lasers e bisturi elétrico), principalmente nas 48 e 72h, tanto na pele quanto na língua. Quanto à quantificação de colágeno, apenas no 7º dia houve diferença estatisticamente significante, ocorrendo maior quantidade de colágeno tipo I somente na incisão com bisturi convencional comparada com a do bisturi elétrico (P < 0.05). No 14º dia, os dados morfométricos de colágeno foram semelhantes em todas as técnicas utilizadas. Concluímos que no período final analisado do processo reparacional, os dados morfométricos foram semelhantes em todas as técnicas utilizadas, apesar das diferenças ocorridas quanto ao dano tecidual, quantificação de mastócitos e colágeno tipo I no início do processo. Em princípio, dentro de um mesmo padrão de incisão, todos os instrumentos cirúrgicos geraram um processo reparacional semelhante, variações entre eles podem estar associadas às características do tecido, como foi observado entre a pele e mucosa. / The aim of this study was to quantify and compare the healing process after incision with CO2 (2 W e 4 W) and diode lasers (2 W and 4 W), electrosurgery (2 W) and scalpel in the skin and tongue of Wistar rats (30 animals were used). One incision of each technique (6 in total) of 5 mm long and 2 mm deep was made in the dorsal skin and dorsal tongue. The animals were sacrificed at zero, 24, 48, 72 hours, 7 and 14 days after incisions. Histological sections were made from the wound areas and subjected to analyses of area of tissue damage, quantification of mast cells and density of collagen type I. The data were submitted to the ANOVA of Kruskal-Wallis and compared by Turkey-Kramer. The level of significance was set at 5% (P < 0.05). The results showed difference concerning area of tissue damage, occurring significant statistically difference between the incisions with scalpel compared with those of other techniques (lasers and electrosurgery) in skin (P < 0.05). On the tongue, there was statistical difference, with less tissue damage on scalpel incision compared with that of CO2 (2 W) and diode lasers (4 W) and electrosurgery incisions (P < 0.05). The quantification of mast in the incisions showed statistical differences between the incisions, especially in 48 and 72h, both on the skin and tongue. Concerning the collagen quantification, statistical difference was found only in 7 th day, the collagen types I was only more evident on scalpel incision than with the electrosurgery (P < 0.05). In 14 th day, the morphometric data were similar in all types of incisions. Based on these results, it is possible to conclude that at the end of the analyzed period, the morphometric data were similar in all techniques, even though there were differences concerning tissue damage, quantification of masts cell and collagen type I at the beginning of the process. Additionally, the healing process proceeds similarly in all this technique as long as the incisions are made in a similar pattern; variations may occur depending on the type of the tissue, as was shown here between the skin and tongue.

A cartilagem articular da cabeça da mandíbula (CAM) é constituída por uma cartilagem secundária recoberta por tecido conjuntivo fibroso e, portanto, definida como fibrocartilagínea. Ela é constantemente submetida a forças de compressão e cisalhamento decorrentes da mastigação necessitando de lubrificação e capacidade de reparo. O envelhecimento é considerado um dos principais fatores para o aparecimento de alterações degenerativas nas articulações sinoviais. A lubricina é reconhecidamente um proteoglicano encontrado nas cartilagens articulares cuja função primordial é a lubrificação limítrofe. A via SMAD2, tem sido associada à capacidade de manutenção e reparo da cartilagem, e a sua fosforilação na cadeia de ligação (p-SMAD2L) foi relacionada ao aumento no tempo de fosforilação na cadeia C-terminal (p-SMAD2) e da transcrição gênica. Objetivo: Estudar as alterações morfológicas da CAM e as expressões da lubricina, p-SMAD2L e do colágeno tipo I no envelhecimento. Métodos: cortes coronais da CAM de ratos wistar com 2, 12 e 24 meses de vida foram corados pelas técnicas da hematoxilina e eosina, azul de toluidina e safranina-O. A imuno-histoquímica foi usada para detectar a localização da lubricina, p-SMAD2L e colágeno tipo I. Resultados: Notou-se modificações estruturais atribuídas ao processo natural do envelhecimento da CAM. Ainda, se verificou um aumento do colágeno tipo I nas camadas mais profundas e cartilaginificação da matriz extracelular (MEC) nas camadas superficiais. No grupo idoso, houve redução na concentração de proteoglicanos, na expressão da lubricina e na densidade e porcentagem de células p-SMAD2L. Conclusões: a CAM sofre modificações com o envelhecimento, inclusive degenerativas, e diminui sua capacidade de lubrificação e reparo em virtude da menor expressão da lubricina e p-SMAD2L. Sugere-se que a p-SMAD2L está envolvida na produção e acúmulo da lubricina na CAM / The mandibular condylar cartilage (MCC) consists of a secondary cartilage covered by fibrous connective tissue and, therefore, defined as fibrocartilage. It is constantly subjected to compression and shear forces resulting from chewing requiring lubrication and repair capability. Aging is considered one of the main factors for the appearance of degenerative changes in synovial joints. Lubricin is a proteoglycan found in articular cartilages whose primary function is boundary lubrication. SMAD2 signaling pathway has been associated with cartilage maintenance and repair, and its phosphorylation in the linker region (p-SMAD2L) was related to the increase in half-life of C-terminal phospho-SMAD2 (p-SMAD2) and gene transcription. Objective: To study the morphological alterations of MCC and the expressions of the lubricin, p-SMAD2L and type I collagen in aging. Methods: Coronal sections of the MCC from wistar rats with 2, 12 and 24 months old were stained with hematoxylin and eosin, toluidine blue and safranin-O. Immunohistochemistry were used for detection of lubricin, p-SMAD2L and type I collagen. Also, the total cell density, p-SMAD2L cells density and percentage were determined. Results: Structural modifications of the MCC related with natural aging process were observed. An increase in the expression of type I collagen in the deeper layers and \"cartilaginification\" of the extracellular matrix (ECM) in the superficial layers were detected. In the old group, it was observed a reduction in proteoglycan content, in the expression of the lubricin and in the density and percentage of positive cells for the p-SMAD2L. Conclusion: MCC undergoes structural and degenerative modifications with aging and decreases its lubrication and repair capacity due to the lower expression of the lubricin and p-SMAD2L. This study suggests that p-SMAD2L is involved in the production and accumulation of the lubricin in MCC

Abstract Matrix metalloproteinases, MMPs, are a family of enzymes capable of modulating connective tissue components. The expression of several MMPs is increased in oral squamous cell carcinomas (OSCCs). They are assumed to have an important role in the development and progression of OSCCs. However, the exact role and mechanism of the regulation of MMPs in malignant transformation are still largely unknown. In this study, tumour-associated trypsin-2 (TAT-2) was detected in OSCC tissue sections, and its role in MMP-2 and -9 regulation in carcinoma cells was evaluated. The TAT-2 gene was transfected into two different OSCC cell lines and one immortalized oral epithelial cell line. In TAT-2-transfected cells, MMP-9 activation increased OSCC cell invasion in chicken chorionallantoic membrane assay. Increased intravasation was prevented by tumour-associated trypsin inhibitor or specific gelatinase-inhibiting CTT-peptide. TAT-2 also converted MMP-1, -8, -13 and -3 into smaller molecular weight forms in vitro. However, TAT-2-transfected OSCC cells showed no conversion. TAT-2 was demonstrated to degrade powerfully type I collagen into small fragments in vitro. The cell surface receptor αvβ6 integrin is strongly up-regulated in OSCCs. By using β6-transfected OSCC cells, it was demonstrated that αvβ6 integrin down-regulates MMP-13 expression. However, this integrin did not regulate other collagenases or TIMP-1. β6-transfected cells invaded more efficiently through the basement membrane matrix, but their migration through type I collagen remained unchanged. MMP-8 expression was detected for the first time in head and neck squamous cell carcinoma (HNSCC) cell lines and corresponding cultured dermal and tumour fibroblasts. The localization of MMP-8 in HNSCC was determined by immunohistochemical stainings and in situ hybridization. MMP-8 production levels in carcinoma cells were faint and sporadic in HNSCCs sections. Ninety-two primary mobile tongue SCCs were subjected to MMP-8 immunohistochemical staining, and the staining results were compared to survival rates. MMP-8 was associated with improved disease-free survival in females but not in males.

Abstract A non-ischemic etiology of sudden cardiac death (SCD), mostly due to various cardiomyopathies (CMP), accounts for about 20% of all SCDs. Most of the major studies of risk factors for SCD have focused on coronary artery disease (CAD). The aim of the present study was to clarify the characteristics of non-ischemic SCD in Northern Finland. In this study, consecutive victims of SCD (n=2661) were prospectively collected, and among whom post-mortem examinations were performed between 1998 and 2007. Information about the SCD victims was obtained from a combination of available medical records, postmortem examination reports, medication used at the time of SCD, and standardized questionnaire filled out by the closest family members of the victims of SCD. We also screened the candidate genes from a Finnish family in which fatal arrhythmias was first manifestation of a cardiac disease. The collagen content of the myocardium from histological samples in victims of SCD due to idiopathic myocardial fibrosis (IMF) was also evaluated. CAD was the most common cause of death (2082 victims, 78.2%). The prevalence of non-ischemic SCDs was 21.8% of all the SCDs. After sub-grouping the non-ischemic SCDs into various categories, the most common cause of death was CMP related to obesity (23.7%), followed by alcoholic CMP (19.0%), hypertensive CMP (15.5%) and IMF (13.6%). The association of SCD with IMF is notably frequent among victims &#60;40 years old (28.3%). The prevalence of family history of SCD was significantly higher in the victims of ischemic (34.2%) than non-ischemic SCD (13.4%, P&#60;0.001) or controls (17.6%, P&#60;0.001). Lamin A/C gene mutation R541C was found from Finnish SCD family, in which the IMF was predominant pathologic-anatomic finding. Myocardial type I collagen synthesis was increased in victims of SCD due to IMF. In conclusion, the characteristics of non-ischemic SCD in Finland differ from those reported previously. Higher prevalences of CMP-associated SCDs related to obesity, IMF and alcoholic CMP were observed as clinical and/or pathologic bases for non-ischemic SCD. The family history of SCD is not significantly increased in victims of non-ischemic SCD, suggesting a larger role of sporadic occurrence than inherited traits as the cause of non-ischemic SCD. Replacement of cardiac myocytes by fibrosis can be responsible for fatal cardiac arrhythmias in subjects with the lamin A/C gene mutation. The victims of SCD due to IMF have increased myocardial type I collagen synthesis. / Tiivistelmä Ei-iskeeminen sydänperäinen äkkikuolema aiheuttaa noin 20&#160;% kaikista sydänperäisistä äkkikuolemista. Suurin osa ei-iskeemisistä sydänperäisistä äkkikuolemista johtuu erilaisista sydänlihassairauksista, kardiomyopatioista. Useimmat sydänperäisen äkkikuoleman riskitekijöitä kartoittavista tutkimuksista ovat keskittyneet sepelvaltimotautiin. Tämän tutkimuksen tarkoituksena oli selvittää ei-iskeemisen sydänperäisen äkkikuoleman tunnuspiirteitä pohjoissuomalaisessa väestössä. Tutkimuksessa käytettiin potilasaineistona sydänperäiseen äkkikuolemaan menehtyneitä vainajia (n=2661), joille on tehty oikeuslääketieteellinen ruumiinavaus. Tiedot vainajista saatiin saatavilla olevista potilaskertomuksista, ruumiinavauspöytäkirjoista, äkkikuoleman aikaisesta lääkityksestä ja lähiomaisille lähetetystä standardisoidusta kyselylomakkeesta. Kandidaattigeenit tutkittiin pohjoissuomalaisesta perheestä, jossa ensimmäinen oire sydänsairaudesta oli hengenvaarallinen rytmihäiriö. Lisäksi sydänlihaksen kollageenikoostumus analysoitiin histologisista näytteistä potilailta, joiden sydänperäinen äkillinen kuolema johtui idiopaattisesta sydänlihaksen sidekudoskasvusta. Sepelvaltimotauti oli yleisin sydänperäisen äkkikuoleman aiheuttaja (n=2082, 78,2&#160;%). Ei-iskeemisten sydänperäisten äkkikuolemien osuus oli 21,8&#160;% (n=579) kaikista sydänperäisistä äkkikuolemista. Ei-iskeemiset sydänperäiset äkkikuolemat jaettiin alaryhmiin, joista yleisimmät olivat lihavuuteen assosioituva kardiomyopatia (23,7&#160;%), alkoholikardiomyopatia (19,0&#160;%), korkeaan verenpaineeseen assosioituva kardiomyopatia (15,5&#160;%) sekä idiopaattinen sydänlihaksen sidekudoskasvu (13,6 %), joka myös oli yleisin ei-iskeemiseen sydänperäiseen äkkikuolemaan johtava syy alle 40-vuotiailla (28,3&#160;%). Positiivinen sydänperäisen äkkikuoleman sukuhistoria oli tilastollisesti merkitsevästi yleisempää iskeemisillä (34,2&#160;%) kuin ei-iskeemisillä (13,4&#160;%) sydänperäisen äkkikuoleman uhreilla. Lamin A/C – geenin mutaatio löydettiin pohjoissuomalaisesta äkkikuolemaperheestä, jossa idiopaattinen sydänlihaksen sidekudoskasvu todettiin pääasialliseksi patologiseksi löydökseksi. Tyypin I kollageenin synteesi todettiin kohonneeksi idiopaattiseen sydänlihaksen sidekudoskasvuun menehtyneillä vainajilla. Yhteenvetona voidaan todeta, pohjoissuomalaisen väestön ei-iskeemisen sydänperäisen äkkikuoleman tunnuspiirteet eroavat aiemmin raportoiduista; lihavuuteen assosioituva kardiomyopatia, alkoholikardiomyopatia, sekä idiopaattinen sydänlihaksen sidekudoskasvu olivat aiempaa yleisempiä ei-iskeemisen äkkikuoleman aiheuttajia. Positiivinen sydänperäisen äkkikuoleman sukuhistoria ei ollut tilastollisesti merkitsevästi kohonnut ei-iskeemisen sydänperäiseen äkkikuolemaan menehtyneillä. Tämä tarkoittaa, että perinnöllinen syy ei-iskeemisen sydänperäisen äkkikuoleman aiheuttajana on luultua harvinaisempi. Lamin A/C – geenimutaation kantajilla sydänlihassolujen korvautuminen sidekudoksella todettiin hengenvaarallisen rytmihäiriön aiheuttajaksi. Lisäksi, tyypin I kollageenin synteesi todettiin kohonneeksi idiopaattiseen sydänlihaksen sidekudoskasvuun menehtyneillä vainajilla.

A number of studies have demonstrated the pivotal role of collagen in modulating cell growth and differentiation. In bone, where the extracellular matrix is composed of approximately 85% type I collagen, cellular interaction with matrix components has been shown to be important in the regulation of the osteoblast phenotype. Preservation or enhancement of normal osteoblast function and appositional bone formation after implant placement represents a strategy that can be useful for the purpose of improving osseointegration. In order to further improve biocompatibility, we combined two known favorable compounds, namely the titanium alloy, Ti6A14V, with type I collagen. We assessed the in vitro behavior of primary osteoblasts grown on both fibrillar collagen-coated and tropocollagen-coated Ti6A14V in comparison with uncoated titanium alloy, using an improved adsorption procedure. As parameters of biocompatibility, a variety of processes, including cell attachment, spreading, cytoskeletal organization, focal contact formation, proliferation and expression of a differentiated phenotype, were investigated. Our results demonstrated for the first time that in comparison to uncoated titanium alloy, collagen-coated alloy enhanced spreading and resulted in a more rapid formation of focal adhesions and their associated stress fibers. Growing on collagen-coated Ti6A14V, osteoblasts had a higher proliferative capacity and the intracellular expression of osteopontin was upregulated compared to uncoated titanium alloy. Type I collagen-coated titanium alloy exhibits favorable effects on the initial adhesion and growth activities of osteoblasts, which is encouraging for its potential use as bone graft material. Moreover, collagen type I may serve as an excellent biocompatible carrier for osteotropic factors such as cell adhesion molecules (e.g. fibronectin) or bone-specific growth factors. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Les phosphates de calcium sont des biomatériaux couramment utilisés dans de nombreuses spécialités médicales. L'amélioration de ces biomatériaux vise à augmenter leur ostéointégration et leur bioactivité. Le strontium possédant d'intéressantes capacités de modification de la physiologie osseuse, l'incorporation de ce dernier au sein de phosphates de calcium par substitution ionique pourrait permettre un déplacement de la balance osseuse vers la formation osseuse.Notre travail a permis de démontrer la capacité des particules de phosphates de calcium substitués en strontium à augmenter la prolifération des ostéoblastes en culture et à modifier l'expression et la synthèse des principales protéines impliquées dans la physiologie osseuse (Collagène de type I, Serpine H1, métalloprotéinases matricielles 1 et 2, inhibiteurs tissulaires des MMPs). Par ailleurs, la poudre de phosphates de calcium ne contenant pas de strontium a entrainé une sécrétion accrue de chimiokines pro-inflammatoires (MCP-1 et GRO-?) qui n'a pas été observée pour la poudre substituée. Enfin, des études in-vivo réalisées dans un modèle de défaut osseux murin a permis de démontrer une plus grande résorbabilité de la poudre contenant du strontium et sa plus grande capacité à stimuler la réparation osseuse. / Calcium phosphate are widely used in medicine. Their upgrade tend to enhance their biocompatibility and their bioactivity. Strontium has interesting capability to modify the bone physiologie. Its incorporation in calcium phosphates could lead to modify the bone balance toward osteogenesis.The present work reveal the capacities of such biomaterials to enhance the replication of osteoblasts ant to modify the expression and the synthesis of proteins implicated in the bone balance (type I collagen, serpinH1, Matrix metalloproteinases 1 and 2, tissular inhibitors of MMPs). Moreover, non substituted calcium phosphate powders enhance the expression and synthesis of inflammatory cytokines (MCP-1 and Gro-a). This fact was not observed with the non substituted powder. In-vivo studies on a mouse model permit us to demonstrate the higher resorbability and the higher bone healing capability of the substituted powder.