Introducción: analizamos la relación entre fracturas y densidad mineral ósea (DMO) y los SNP (polimorfismos de un solo nucleótido) rs3102735 (163 A/G), rs3134070 (245 T/G) y rs2073618 (1181 G/C) de OPG, el SNP rs2277438 SNP de RANKL, el SNP rs7121 (393 T/C) de GNAS1 y del SNP rs219780 del gen CLDN14 en pacientes con HPP (hiperparatiroidismo primario) esporádico. Métodos: reclutamos 298 pacientes con HPP y 328 voluntarios sanos en un estudio transversal. Analizamos historia de fracturas o litiasis renal, parámetros bioquímicos, DMO en columna lumbar, cadera total, cuello femoral y radio distal y genotipado de los SNP mencionados. Resultados: no encontramos diferencias entre los genotipos de ninguno de los SNP estudiados en relación con la frecuencia de fracturas en HPP o en sujetos control. La DMO fue menor en el radio en los HPP homocigotos para el alelo menor en comparación con el resto de grupos en los SNP de OPG (163 A/G) y (245 T/G) pero no en sujetos control. En el resto de los SNP estudiados no encontramos diferencias entre genotipos y DMO en los sujetos con HPP o control excepto en el SNP de OPG (1181 G/C) en sujetos control con mayor DMO lumbar en el grupo CC respecto del GG. Conclusiones: los sujetos con HPP y homocigotos para el alelo menor (GG) en los SNP rs3102735 (163 A/G) y rs3134070 (245 T/G) de OPG tienen menor DMO en el radio distal. El resto de SNP estudiados no parecen influir en la diferente expresión de las manifestaciones óseas del HPP. / Background: we analyze the relationship between fractures and BMD (bone mineral density) and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG, the rs2277438 SNP of the RANKL, the rs7121 SNP (393 T/C) of GNAS1 and the rs219780 of CLDN14 in patients with sporadic PHPT (primary hyperparathyroidism). Methods: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed history of fractures or renal lithiasis, biochemical determinants, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied. Results: Regarding the frequency of fractures we found no differences between genotypes in any of the SNPs studied in the PHPT or in the control subjects groups. Significant lower BMD in the distal radius was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT but not in control subjects. We found no difference between genotypes of the rest of the SNPs studied in PHPT or control subjects with the exception of SNP OPG rs2073618 (1181 G/C) in control CC subjects which showed higher lumbar BMD than GG ones. Conclusions: Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius. All the other SNPs studied do not appear to influence the different expression of HPP in bone.

Många sjöar är idag påverkade av mänsklig aktivitet, bland annat är 1 % av Sveriges sjöar eutrofierade, däribland Ekoln. Ekoln är en stor sjö i Uppsala län söder om Uppsala som länge varit eutrofierad. Fyrisån och Örsundaån är de största inflödena till Ekoln och Sävjaån är ett betydande biflöde till Fyrisån. Kungsängsverket är Uppsalas reningsverk och har sitt utlopp i Fyrisån och som ett led i att minska eutrofieringen byggdes fosforreningen ut 1972. Fosforhalterna i Ekoln sjönk och algblomningarna blev färre. Kvävereningen byggdes ut 1999 och i detta arbete utvärderas detta reningssteg.   Hypotesen är att när ammonium minskar i bottenvattnet kommer syrgasförhållandena att förbättras på grund av minskad ammoniumnedbrytning som förbrukar syrgas. Med ökad halt syrgas är det känt sedan tidigare studier att den interna fosforbelastningen och algblomningen minskar.   För att undersöka om det skett en signifikant minskning av näringsämnen i intransporten till Ekoln och av halterna i Ekoln utfördes statistiska test av ämnena för perioden före och perioden efter införandet av kväverening. Intransporterna modellerades även i StormTac.   Resultatet visar att det skett en minskning av kväve- och ammoniumtransport och en ökning av fosfor-, fosfat- och TOC-transport. I Ekoln har en minskning påvisats i ammonium-, totalfosforhalt och en ökning i fosfat- och TOC-halt. Ammoniumhalten har minskat i bottenvattnet så den minskade intransporten av ammonium gett en effekt. Fosfor- och fosfathalten har inte förändrats signifikant i bottenvattnet, men det har skett en viss minskning av fosfor och en viss ökning av fosfat i Ekoln perioden 1990-1998 till 2000-2010. Även syrgashalten har ökat i bottenvattnet.   Att det inte skett signifikanta förändringar i fosfor, fosfat och syrgas tyder på att intransporten till vattenmassan inte förändrats. Ökade TOC-halter leder till ökad nedbrytning där syrgas förbrukas i bottenvattnet. Det är möjligt att situationen sett ännu värre ut i Ekoln om inte kväveutsläppen minskat.

Das RANKL/RANK/OPG-System spielt eine entscheidende Rolle in der Steuerung der Osteoklastendifferenzierung und -aktivierung durch Osteoblasten/ Knochenmarkbindegewebszellen im Rahmen des Knochenremodelings. Osteoblasten/Knochenmarkbindegewebszellen exprimieren RANKL. Dieses hat im Körper zwei Rezeptoren: RANK und OPG. RANKL kann durch Bindung an RANK auf Osteoklasten/Osteoklastenvorläuferzellen in Gegenwart von M-CSF seine osteoklastenstimulierende Wirkung entfalten. Der ebenfalls von Osteoblasten gebildete „decoy“-Rezeptor OPG blockiert als freies Protein durch Bindung an RANKL dessen Interaktion mit RANK und verhindert somit die Osteoklastogenese und Osteoklastenaktivierung. Das RANKL/RANK/OPG-System erfüllt im Körper noch weitere Funktionen im Immunsystem, in der Organentwicklung lymphatischer Gewebe und in der Entwicklung der laktierenden Brustdrüse. Viele Zytokine greifen hemmend oder aktivierend in die Osteoklastogenese ein. Sie können dies zum einen durch die Beeinflussung des RANKL/OPG-Verhältnisses, zum anderen durch direkte Interaktion mit Osteoklasten/Osteoklastenvorläuferzellen tun. Zytokine, die die Osteoklastogenese begünstigen, werden vor allem bei inflammatorischen Prozessen ausgeschüttet. Zusammen mit dem, bei diesen Zuständen von aktivierten T-Zellen produzierten RANKL kann dies längerfristig zu einem Knochenverlust führen, welcher sich im klinischen Bild der Osteoporose äußert. Aus den in der vorliegenden Dissertation durchgeführten Untersuchungen ergeben sich folgende Schlussfolgerungen: 1. Monozyten der Zelllinie RAW 264.7 lassen sich, wie bereits in der Literatur beschrieben, durch Zugabe von M-CSF und RANKL zu osteoklastenähnlichen Zellen differenzieren. 2. Die Osteoklastogenese lässt sich anhand der Veränderung verschiedener osteoklastenspezifischer Parameter charakterisieren. Es zeigt sich bei den mit M-CSF und RANKL stimulierten Monozyten eine erhöhte Transkription von CTR (Calcitoninrezeptor)- und TRAP (tartratresistente saure Phosphatase)-mRNA, eine erhöhte Expression des CTR-Proteins, eine erhöhte TRAP-Aktivität und eine Formierung TRAP-positiver mehrkerniger Riesenzellen, die in diesen Eigenschaften Osteoklasten entsprechen. Die zusätzliche Zugabe von TGF-b1 in Kombination mit M-CSF und RANKL resultiert in einer verstärkten Expression von CTR-mRNA und CTR-Protein. TRAP-mRNA-Expression und TRAP-Aktivität bleiben davon unbeeinflusst. 3. Als funktionelles Merkmal der in vitro differenzierten Osteoklasten können ihre Fähigkeit zur Ausbildung von Aktinringen und die Resorption von mineralisiertem Kollagen nachgewiesen werden. 4. Im Verlauf ihrer Differenzierung sekretieren Osteoblasten unterschiedliche Mengen an OPG. Das Maximum der Synthese liegt bei Tag 11. Freies RANKL lässt sich in Überständen von MC3T3-E1-Osteoblasten nicht nachweisen. 5. Das von Osteoblasten in das Medium abgegebene OPG ist in der Lage, die durch RANKL induzierte Osteoklastogenese von RAW-Monozyten zu hemmen. 6. In Kokulturen von MC3T3-E1-Osteoblasten und RAW-Monozyten kann keine Osteoklastogenese beobachtet werden, wahrscheinlich durch Fehlen der RANKLExprimierung oder zu starke OPG-Sekretion durch Osteoblasten. Besonders in der westlichen Welt mit ihrer hohen Lebenserwartung haben Krankheiten mit Knochenverlust sowie bösartige Neubildungen mit Knochenbefall eine große medizinische Bedeutung. Die Beeinflussung des RANKL/RANK/OPG-Systems bietet eine vielversprechende Möglichkeit zur Entwicklung hochwirksamer und nebenwirkungsarmer Medikamente zur Behandlung dieser Zustände.

Ensembles are today routinely applied to estimate uncertainty in numerical predictions of complex systems such as the weather. Instead of initializing a single numerical forecast, using only the best guess of the present state as initial conditions, a collection (an ensemble) of forecasts whose members start from slightly different initial conditions is calculated. By varying the initial conditions within their error bars, the sensitivity of the resulting forecasts to these measurement errors can be accounted for. The ensemble approach can also be applied to estimate forecast errors that are due to insufficiently known model parameters by varying these parameters between ensemble members. An important (and difficult) question in ensemble weather forecasting is how well does an ensemble of forecasts reproduce the actual forecast uncertainty. A widely used criterion to assess the quality of forecast ensembles is statistical consistency which demands that the ensemble members and the corresponding measurement (the ``verification\'\') behave like random independent draws from the same underlying probability distribution. Since this forecast distribution is generally unknown, such an analysis is nontrivial. An established criterion to assess statistical consistency of a historical archive of scalar ensembles and verifications is uniformity of the verification rank: If the verification falls between the (k-1)-st and k-th largest ensemble member it is said to have rank k. Statistical consistency implies that the average frequency of occurrence should be the same for each rank. A central result of the present thesis is that, in a statistically consistent K-member ensemble, the (K+1)-dimensional vector of rank probabilities is a random vector that is uniformly distributed on the K-dimensional probability simplex. This behavior is universal for all possible forecast distributions. It thus provides a way to describe forecast ensembles in a nonparametric way, without making any assumptions about the statistical behavior of the ensemble data. The physical details of the forecast model are eliminated, and the notion of statistical consistency is captured in an elementary way. Two applications of this result to ensemble analysis are presented. Ensemble stratification, the partitioning of an archive of ensemble forecasts into subsets using a discriminating criterion, is considered in the light of the above result. It is shown that certain stratification criteria can make the individual subsets of ensembles appear statistically inconsistent, even though the unstratified ensemble is statistically consistent. This effect is explained by considering statistical fluctuations of rank probabilities. A new hypothesis test is developed to assess statistical consistency of stratified ensembles while taking these potentially misleading stratification effects into account. The distribution of rank probabilities is further used to study the predictability of outliers, which are defined as events where the verification falls outside the range of the ensemble, being either smaller than the smallest, or larger than the largest ensemble member. It is shown that these events are better predictable than by a naive benchmark prediction, which unconditionally issues the average outlier frequency of 2/(K+1) as a forecast. Predictability of outlier events, quantified in terms of probabilistic skill scores and receiver operating characteristics (ROC), is shown to be universal in a hypothetical forecast ensemble. An empirical study shows that in an operational temperature forecast ensemble, outliers are likewise predictable, and that the corresponding predictability measures agree with the analytically calculated ones.

KRAS is a gene that plays a very important role in the initiation and development of several types of cancer. In particular, 90% of human pancreatic cancers are due to KRAS mutations. KRAS is difficult to target directly and a promising therapeutic path is its indirect inactivation by targeting one of its Synthetic Lethal Partners (SLPs). A gene G is a Synthetic Lethal Partner of KRAS if the simultaneous perturbation of KRAS and G leads to cell death. In the past, efforts to identify KRAS SLPs with high-throughput RNAi screens have been performed. These studies have reported only few top-ranked SLPs. To our knowledge, these screens have never been considered in combination for further examination. This thesis employs integrative analysis of the published screens, utilizing additional, independent data aiming at the detection of more robust therapeutic targets. To this aim, RankSLP, a novel statistical analysis approach was implemented, which for the first time i) consistently integrates existing KRAS-specific RNAi screens, ii) consistently integrates and normalizes the results of various ranking methods, iii) evaluates its findings with the use of external data and iv) explores the effects of random data inclusion. This analysis was able to predict novel SLPs of KRAS and confirm some of the existing ones.

No description available.

The behavior of rank procedures in measurement error models was studied - if tests and estimates stay valid and applicable when there are some measurement errors involved and if not how to modify these procedures to be able to do some statistical inference. A new rank test for the slope parameter in regression model based on minimum distance esti- mator and an aligned rank test for an intercept were proposed. The (asymptotic) bias of R-estimator in measurement error model was also investigated. Besides measurement errors the problem of heteroscedastic model errors was considered - regression rank score tests of heteroscedasticity with nuisance regression and tests of regression with nuisance heterosce- dasticity were proposed. Finally, in location model tests and estimates of shift parameter for various measurement errors were studied. All the results were derived theoretically and then demonstrated numerically with examples or simulations.

Objetivo: investigar a capacidade osteoclastogênica de células mononucleares do sangue periférico (PBMCs) de pacientes do sexo masculino com espondilite anquilosante (EA), comparando com indivíduos saudáveis e determinar a relação da osteoclastogênese com parâmetros clínicos e laboratoriais. Métodos: células mononucleares do sangue periférico de 85 pacientes com espondilite anquilosante e 59 controles saudáveis (CT) foram marcadas para avaliar a presença de células CD16 positivas (precursores de osteoclastos). As PBMCs foram mantidas, in vitro, por 21 dias para indução da diferenciação em osteoclastos e avaliação da apoptose destas células. Os níveis séricos do ligante do receptor ativador de fator nuclear kB (RANKL), osteoprotegerina (OPG), telopeptídeo C-terminal do colágeno tipo I (CTX) e propeptídeo Nterminal do procolágeno tipo I (P1NP) foram também avaliados. Resultados: PBMCs de pacientes com EA apresentaram menor porcentagem de células CD16 positivas (25,06 ± 8,59 vs. 28,59 ± 10,20%; p = 0,026) e originaram menor número de osteoclastos comparados aos controles saudáveis (647,7 ± 669,4 vs. 764,4 ± 561,9 OC/poço; p = 0,014). A porcentagem de osteoclastos em apoptose foi menos frequente nos pacientes com EA versus CT (31,8 ± 32,5 vs. 44,5 ± 34,3%; p = 0,007). Menores relações RANKL/OPG e CTX/P1NP foram observadas nos pacientes com EA em relação aos CT (0,05 ± 0,03 vs. 0,07 ± 0,07; p = 0,046 e 0,008 ± 0,003 vs. 0,010 ± 0,003; p < 0,001, respectivamente). Pacientes com EA em uso de terapia de anti-inflamatório não-hormonal (AINH) não apresentaram diferença associada ao número de osteoclastos gerados e à porcentagem de células CD16 positivas comparados aos CT (p > 0,05). Entretanto, pacientes com EA em uso de terapia com inibidor de TNFalfa (iTNFalfa) demonstraram menor número de osteoclastos gerados comparados aos indivíduos saudáveis (582,51 ± 717,56 vs. 764,43 ± 561,9 OC/poço; p = 0,047). Observou-se uma correlação negativa entre número de osteoclastos gerados a partir de PBMC de pacientes com EA e duração de doença (R = -0,220, p = 0,043). Conclusões: os presentes resultados demonstraram que monócitos de pacientes com EA apresentam uma menor capacidade em gerar osteoclastos comparados a indivíduos saudáveis, e que a osteoclastogênese esteve correlacionada negativamente à duração de doença. Estes dados sugerem que os osteoclastos possuem um papel importante na fisiopatologia da doença óssea nos pacientes com EA / Objective: the aim of this study was to investigate if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters. Methods: PBMCs from 85 male ankylosing spondylitis (AS) patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3 weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type 1 collagen (P1NP) were also evaluated. Results: PBMCs from AS patients had fewer CD16+ cells (25.06 ± 8.59 vs. 28.59 ± 10.20%; p = 0.026) and produced fewer osteoclasts (647.7 ± 669.4 vs. 764.4 ± 561.9 OC/well; p = 0.014) compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls (31.8 ± 32.5 vs. 44.5 ± 34.3%; p = 0.007). A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls (0.05 ± 0.03 vs. 0.07 ± 0.07; p = 0.046 e 0.008 ± 0.003 vs. 0.010 ± 0.003; p < 0.001, respectively). AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls (p > 0.05). However, patients taking TNFalpha inhibitors (TNFi) presented lower OC numbers than controls (582.51 ± 717.56 vs. 764.43 ± 561.9 OC/well; p = 0.047). A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration (R = -0.220, p = 0.043). Conclusion: monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-10-02T15:28:01Z No. of bitstreams: 2 Dissertação - Mateus Ferreira e Freitas - 2017.pdf: 4269845 bytes, checksum: e84e69d8747a21125170793812384a98 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-10-02T15:30:07Z (GMT) No. of bitstreams: 2 Dissertação - Mateus Ferreira e Freitas - 2017.pdf: 4269845 bytes, checksum: e84e69d8747a21125170793812384a98 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-10-02T15:30:07Z (GMT). No. of bitstreams: 2 Dissertação - Mateus Ferreira e Freitas - 2017.pdf: 4269845 bytes, checksum: e84e69d8747a21125170793812384a98 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-08-30 / Several applications process documents in different ways, aiming to filter, organize or learn with them. Nowadays, a great computational power is necessary in order to do that efficiently, due to the large and increasing number of documents. Usually, documents are independent of each other, which facilitates the use of parallelism to speed up this processing. This work explores three problems: active learning, learning to rank (L2R) and top-k search. Using the parallelism on multicore CPUs and manycore GPUs (Graphics Processing Unit), parallel algorithms were proposed and evaluated for each problem, and implemented with the OpenMP and CUDA APIs. For the active learning problem a multicore algorithm was proposed, which obtained 10.8x of speedup in the best case with 12 threads. The proposed manycore version obtained 128x of speedup over the serial version, and a solution with 4 GPUs achieved 3.5x of speedup over 1 GPU. For the L2R problem a manycore algorithm was proposed, which follows a thread-block approach using the concept of Combinadic, and uses a cache with fingerprint to speed up the processing. The best case speedups were 508x over the serial, 9x over a GPU baseline, and 4x over our solution when using 4 GPUs. When comparing with a version without combinadic, the speedup over it was 4.4x with both versions using 1 GPU and 3.9x with 4. These solutions used bitmap structures to speed up the association rules creation. In the top-k search a serial and multicore solutions were implemented from a state of the art manycore algorithm for exact searches. These implementations served as baselines for our extension of this algorithm, which includes the use of multi-GPU, group searches and an intra-block load balancing. The speedups were 2.7x over the original algorithm, 17x over the serial, 4x over the multicore, and 4x over our version when using 4 GPUs. / Diversas aplicações processam documentos de diferentes maneiras, visando filtrá-los, organizá-los ou aprender com eles. Atualmente, é necessário um grande poder computacional para que isso seja feito eficientemente, devido ao número grande e crescente de documentos. Geralmente os documentos são independentes entre si, o que facilita o uso de paralelismo para acelerar esse processamento. Este trabalho explora três problemas: aprendizado ativo, learning to rank (L2R) e busca top-k. Usando o paralelismo em CPUs multicore e GPUs (Graphics Processing Unit) manycore, algoritmos paralelos foram propostos e avaliados para cada problema, e implementados com as APIs OpenMP e CUDA. Para problema de aprendizado ativo foi proposto um algoritmo multicore, que obteve speedup de 10,8x no melhor caso com 12 threads. A versão manycore proposta obteve speedup de 128x em relação ao serial, e uma solução com 4 GPUs atingiu 3,5x de speedup sobre 1 GPU. Para o problema de L2R foi proposto um algoritmo manycore, que segue uma abordagem por bloco de threads} usando o conceito de Combinadic, e usa uma cache} com fingerprint para acelerar o processamento. Os speedups nos melhores casos foram de 508x sobre o serial, 9x sobre uma baseline em GPU, e 4x sobre nossa solução com 1 GPU ao usar 4 GPUs. Ao comparar com uma versão sem o combinadic, o speedup sobre ela foi de 4,4x com ambas versões usando 1 GPU e 3,9x usando 4. Estas soluções usaram estruturas de mapa de bits para acelerar a criação de regras de associação. Na busca top-k foram implementadas uma solução serial e uma multicore de um algoritmo manycore estado da arte para buscas exatas. Estas implementações serviram de baseline para nossa extensão desse algoritmo, que inclui o uso de multi-GPU, buscas em grupos e um balanceamento de carga intra-bloco. Os speedups obtidos foram de 2,7x sobre o algoritmo original, 17x sobre o serial, 4x sobre o multicore, e 4x sobre nossa versão ao usar 4 GPUs.

Os mini-implantes ortodônticos vem sendo amplamente utilizados na prática clínica como dispositivos de ancoragem. No entanto, há casos em que ocorre sua perda durante o tratamento. Inúmeros aspectos tem sido analisados com o intuito de detectar as causas do insucesso, porém estas ainda não estão totalmente esclarecidas. Portanto, utilizando-se dois grupos de mini-implantes - com estabilidade (sucesso) e sem estabilidade (falha) -, os objetivos do presente estudo in vivo foram: 1) avaliar a contaminação microbiana, empregando sondas de DNA para 40 espécies de bactérias, por meio da técnica de biologia molecular checkerboard DNA-DNA hybridization; 2) quantificar a endotoxina bacteriana presente nos mini-implantes dos dois grupos por meio do teste Limulus Amebocyte Lysate ; e 3) quantificar as citocinas pró-inflamatórias IL-1&alpha;, IL-6, IL-17 e TNF-&alpha; e proteínas marcadoras da osteoclastogênese (RANK, RANKL e OPG) por meio da técnica real-time polymerase chain reaction. Dezesseis pacientes de ambos os sexos (11-49 anos) em tratamento ortodôntico com aparelho corretivo e mini-implantes foram selecionados, sendo obtidos 19 miniimplantes com estabilidade e 10 mini-implantes sem estabilidade. O tempo médio de permanência na boca foi de 23,8 meses para os mini-implantes estáveis e 6,7 meses para os mini-implantes sem estabilidade. Foram utilizados mini-implantes da marca Neodent, com 1,6mm de diâmetro e com 7,0 ou 9,0 mm de comprimento, colocados na maxila e/ou mandíbula. Todos os mini-implantes foram instalados e removidos pelo mesmo cirurgião. No momento da remoção, foram coletados os miniimplantes e amostras de gengiva ao redor dos mesmos. Os mini-implantes foram processados para a detecção dos micro-organismos e para a quantificação da endotoxina bacteriana. As amostras de gengiva foram processadas para a quantificação das citocinas pró-inflamatórias e proteínas marcadoras da osteoclastogênese. Os resultados obtidos foram analisados por meio do teste nãoparamétrico de soma de postos de Wilcoxon, considerando-se os conglomerados, utilizando o software SAS. O nível de significância adotado foi de 5%. Todas (100%) as 40 espécies de microorganismos foram observadas em ambos os grupos de mini-implantes, com diferentes porcentagens de ocorrência. Não foi possível observar diferença entre os grupos com relação aos complexos microbianos (azul, roxo, amarelo, verde, laranja, vermelho e outras espécies). Também não foi possível observar diferença na quantificação de endotoxina e das citocinas e marcadores da osteoclastogênese (p>0,05), com exceção da IL-6 (p<0,05). Baseado nos resultados obtidos, pode-se concluir que a contaminação microbiana e a quantidade de endotoxina nos mini-implantes, assim como a expressão das citocinas pró-inflamatórias IL-1&alpha;, IL-17 e TNF-&alpha; e dos marcadores da osteoclastogênese RANK, RANKL e OPG no tecido gengival circundante não atuaram como fatores responsáveis pela perda da estabilidade dos mini-implantes e que a maior expressão da citocina próinflamatória IL-6 pode estar diretamente relacionada à perda da estabilidade dos mini-implantes, sugerindo-se estudos adicionais. / Orthodontic mini-implants have been widely used in clinical practice as anchorage devices. However, their loss may occur during the treatment. Several aspects have been investigated to identify the causes of failure, but they are not yet completely elucidated. Therefore, using two groups of miniimplants - stable and unstable/loose - the objectives of this in vivo study were: 1) to evaluate the microbial contamination, using DNA probes for 40 bacterial species by the checkerboard DNA-DNA hybridization biomolecular technique; 2) to quantify the bacterial endotoxin present in both groups of mini-implants by the Limulus Amebocyte Lysate assay; and 3) to quantify the proinflammatory cytokines IL-1&alpha;, IL-6, IL-17 and TNF-&alpha; and the osteoclastogenesis marker proteins (RANK, RANKL and OPG) by real-time polymerase chain reaction technique. Sixteen patients of both sexes (11 to 49 years old) under orthodontic treatment with corrective appliance and mini-implants were selected, obtaining 19 stable mini-implants and 10 unstable/loose mini-implants. The mean time of permanence in the mouth was 23.8 months for stable mini-implants and 6.7 months for unstable/loose mini-implants. The mini-implants (1.6 mm diameter x 7.0 or 9.0 mm long; Neodent) were placed in the maxilla and/or mandible. All mini-implants were placed and removed by the same surgeon. At the moment of removal, the mini-implants and periimplant gingival tissue samples were collected. The mini-implants were processed for detection of microorganisms and quantification of bacterial endotoxin, while the gingival tissue samples were processed for quantification of proinflammatory cytokines and osteoclastogenesis protein markers. The results were analyzed statistically by the nonparametric Wilcoxon rank-sum test, considering the conglomerates, using SAS software. A significance level of 5% was adopted for all analyses. All (100%) 40 microbial species were observed in both groups of mini-implants, with different percentages of occurrence. No differences could be observed between the groups with respect to the microbial complexes (blue, purple, yellow, green, orange, red and other species). There was no significant difference either in the quantification of endotoxin and cytokines and osteoclastogenesis markers (p>0.05), except for IL- 6 (p<0.05). Based on the obtained results, it may be concluded that neither the microbial contamination and amount of endotoxin in mini-implants, nor the expression of proinflammatory cytokines IL-1&alpha;, IL-17 and TNF-&alpha; and osteoclastogenesis markers RANK, RANKL and OPG in the periimplant gingival tissue acted as factors responsible for the loss of stability of the mini-implants, and that the higher expression of the IL-6 proinflammatory cytokine may be directly associated with the loss of stability of the mini-implants, suggesting additional studies.