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Browsing by Author "Akota, Ilze"

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    Apoptosis and MMP-2, TIMP-2 expression in cleft lip and palate
    (2013) Smane, Liene; Pilmane, Mara; Akota, Ilze; Institute of Anatomy and Anthropology; Department of Morphology; Rīga Stradiņš University
    Aim of our study was complex detection of appearance and distribution of specific signalling proteins and apoptosis in facial tissue of children with complete bilateral cleft lip and palate (CBCLP). MATERIALS AND METHODS. Nineteen CBCLP patients and 11 unaffected subjects were involved in this study. All the tissue samples were proceeded for detection of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and apoptosis. The intensity of immunostaining was graded semi-quantitatively. Results of the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method were obtained by counting apoptosis positive cells in five unintentionally chosen fields of vision. Groups were compared using the Mann-Whitney test. RESULTS. TUNEL-positive oral epithelial cells were significantly increased in the control group when compared with the CBCLP group. Connective tissue cells have a statistically significant lower expression of TIMP-2 in the control group compared to the CBCLP group. CONCLUSIONS. TIMP-2 positive connective tissue cells increasingly found in oral mucosa lamina propria proves the decrease of local apoptosis in CLP patients. Prominent expression of MMP-2 in cleft affected soft tissue indicates a possible increase of tissue remodelling.
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    Appearance and distribution of tissue remodellation factors in the hard tissue of patients affected by cleft lip palate
    (2020-06-01) Buile, Dace; Pilmane, Māra; Akota, Ilze; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    Bone repair after surgical intervention on cleft lip palate (CLP) depends on the coordinated action of multiple tissue regeneration factors. We determined the relative number and appearance of tissue factors: matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic protein 2/4 (BMP 2/4), transforming growth factor beta (TGF-ß), Wnt3a protein (Wnt3a), Runt-related transcription factor 2 (Runx2), basic fibroblast growth factor (bFGF) and osteoprotegerin in hard tissue of CLP patients during first time surgical intervention. Fourtythree CLP patients with 24 bone and 36 cartilage samples were involved. Immunohistochemistry was used to assess the levels of tissue factors and the semi-quantitative census method was used for quantification of immunological structures. The increased amount of MMP-2 and bFGF positive cells was detected in the CLP group in cartilage and bone (p < 0.05), compared to the controls. A statistically significant (p = 0.012) increased amount of BMP 2/4 positive cells was found in cartilage of CLP patients, in comparison to the control group. Increased appearance of MMP-2, bFGF in hard tissue of the CLP patients indicates the predominance of tissue degradation. Increased number of BMP2/4 positive chondrocytes suggests improved cartilage growth and better regeneration in CLP patients.
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    ARTICULATE : A European glossary of terms used in oral health professional education
    (2023-05) Davies, Julia R.; Field, James; Dixon, Jonathan; Manzanares-Cespedes, Maria Cristina; Vital, Sibylle; Paganelli, Corrado; Akota, Ilze; Quinn, Barry; Roger-Leroi, Valerie; Murphy, Denis; Gerber, Gabor; Tubert-Jeannin, Stephanie; Rīga Stradiņš University
    Introduction: The Erasmus+O-Health-EDU project aims to gain a comprehensive view of oral health professional (OHP) education in Europe, through the development of web-based surveys and online toolkits. A glossary to facilitate a common language through which academic teams could cooperate and communicate more accurately was identified as a key need within the project. The aim of ARTICULATE was thus to create a shared language, with a European focus, for terms and concepts used in the field of OHP education. Methods: The methodology was developed from those published for construction of other glossaries with a circular and iterative process: the creation of content and definitions by a group of experts in OHP education, the testing of “fitness for purpose” of the content, and stakeholder consultation. All creation steps were followed by refinements based on testing results and stakeholder comments. The final glossary was then launched as an online resource including a built-in mechanism for user feedback. Results: The scope and structure of the glossary were mapped out at a workshop with 12 dental education experts from 7 European countries. A total of 328 terms were identified, of which 171 were finally included in ARTICULATE. After piloting with a close group of other colleagues, the glossary was opened for external input. Thirty European Deans or Heads of Education assessed the definition of each term as “clear” or “not clear.” A total of 86 definitions were described as “clear” by all individuals. Terms deemed unclear by at least one individual were revisited and changes made to 37 of the definitions. In conjunction with the launch of the glossary, a range of stakeholder organisations were informed and asked to participate in an open global consultation by providing feedback online. Since its launch in June 2021, the ARTICULATE website (https://o-health-edu.org/articulate) has had an average of 500 visits/month. To promote community ownership, forms embedded on the ARTICULATE webpage allow users to give feedback and suggest new terms. A standing taskforce will meet regularly to consider amendments and make changes to ensure that the glossary remains a relevant and up-to-date resource over time. Conclusion: ARTICULATE is a unique, evolving, online glossary of terms relating to OHP education, created as a resource for all interested OHP educators. The glossary is a key output of the O-Health-Edu project, which relies on a comprehensive vision of OHP education to address the future oral health needs of the European population.
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    Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations
    (2014) Kempa, Inga; Ambrozaitytė, Laima; Stavusis, Janis; Akota, Ilze; Barkane, Biruta; Krumina, Astrida; Matulevičienė, Aušra; Utkus, Algirdas; Kučinskas, Vaidutis; Lace, Baiba; Scientific Laboratory of Molecular Genetics; Rīga Stradiņš University
    Cleft lip with or without cleft palate (CLP and CL, respectively) and isolated cleft palate (CP) represent one of the most common human birth defects, with a prevalence of approximately 1 in 300-2500 depending on the population. Formation of non-syndromic CL/CLP and CP arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP4 gene (encoding bone morphogenetic protein 4) and non-syndromic CL/CLP and CP in order to clarify the role of this gene in the aetiology of the malformation in Latvian and Lithuanian populations. We genotyped three markers of the BMP4 gene (rs17563, rs2071047 and rs1957860) in order to perform single marker and haplotype association analyses for Latvian and Lithuanian non-syndromic CL/CLP and CP patients and controls. Transmission disequilibrium test was also conducted for Latvian and Lithuanian proband-parent trios. The case-control analysis revealed that SNP rs2071047 allele A was associated with a decreased risk of CL/CLP in the Latvian population, which was confirmed by the haplotype analysis. A modest association was detected between SNP rs1957860 and CP in the Lithuanian population, where allele C was associated with a decreased risk of this cleft phenotype, corroborating haplotype analysis data. Our findings support a role of the BMP4 gene in the aetiology of non-syndromic CL/CLP and CP in the studied populations.
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    Barx1, growth factors and apoptosis in facial tissue of children with clefts
    (2008) Krivicka-Uzkurele, Benita; Pilmane, Mara; Akota, Ilze; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    OBJECTIVE: Clefts of lip and palate belong to the most common birth defects worldwide. Growth factors and genes play an important role in tissue growth, differentiation and induction and upregulation of growth factors, apoptosis and matrix metalloproteinases might be involved in pathogenesis of facial clefts. The aim of this study was investigation of palate tissue in children with unilateral cleft lip palate for detection of local tissue growth factors, barx1 and apoptosis. MATERIALS AND METHODS:We investigated soft and hard palate tissue from 36 children with complete unilateral cleft lip and palate from cleft area.14 children were in age before and primary dentition, but 22 children were in mixed dentition period. We examined the localization of barx1, FGFR1, NGFR, TGFbeta, BMP2/4, MMP2, PGP 9,5 by immunohistochemistry. TUNEL method was performed for detection of apoptotic cells. RESULTS: Abundance of FGFR1 positive cells was seen almost in all cases. FGFR richly stained cells of soft and hard palate tissue. Abundance of NGFR positive cells was detected in basal epithelium, hair follicles, nerve fibers in wall of blood vessels and subepithelium, and was more often seen in children before mixed dentition. TGFbeta has showed intensive expression in epithelium, cartilage and bone in both dentition ages. Chondrocytes, fibroblasts and macrophages expressed MMP2 predominant before mixed dentition. Regional expression of barx1 was observed in epithelium before the mixed dentition, while during mixed dentition gene appeared in hyaline cartilage. TUNEL discovered apoptosis in both dentition ages. CONCLUSIONS: FGFR1 and TGFbeta are main tissue stimulating growth factors in both dentition ages. Expression of barx1 appears in cleft lip palate affected structures mainly in mixed dentition ages. NGFR and neuropeptides-containing structures are mainly characteristic in cleft tissue before mixed dentition. Distribution of genes, GF and apoptosis seem to correlate rather with dentition age than to type of CLP.
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    Characterization of cytokines and proliferation marker Ki67 in cleft affected lip tissue
    (2019-09) Pilmane, Mara; Sidhoma, Elga; Akota, Ilze; Kazoka, Dzintra; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    Background and objectives: Cleft lip palate takes the second place among all anomalies. The complex appearance of cytokines and proliferation markers has still not been clarified despite their possible crucial role in cleft tissue. Therefore, the aim of work was the detection of appearance of pro- and anti-inflammatory cytokines and proliferation marker Ki67, and their inter-correlations in cleft affected lip (CAL). Materials and Methods: The lip material was obtained from 16 children aged before primary dentition during plastic surgery. Control was obtained from 7 non-CAL oral tissue. Tissues were stained for IL-1, IL-4, IL-6, IL-8, IL-10 and Ki67 immunohistochemically. Nonparametric statistic, Mann-Whitney and Spearman’s coefficient were used. Results: All cytokines positive cells were observed more into the epithelium. Statistically significant difference was seen between epithelial IL-1, IL-10, IL-8 and Ki67 positive cells and IL-10-, IL-4-containing connective tissue cells in comparison to the control. Strong positive correlation was detected in CAL epithelium between IL-10 and IL-8, IL-10 and IL-4, IL-10 and IL-1, IL-1 and IL-8, IL-1 and IL-4, IL-4 and IL-8, IL-8 and Ki67, IL-10 and Ki67, but moderate-in connective tissue between IL-1 and IL-10, IL-1 and IL-4. Conclusion: The CAL epithelium is the main source for the interleukins. Rich similar expression of IL-1 and IL-10 suggests the balance between pro-and anti-inflammatory tissue response on basis of dysregulated tissue homeostasis (increase of IL-8). The correlations between the different ILs -1, -4, -8, -10 in CAL epithelium seem to indicate the self-protection compensatory mechanism for intensification of local inflammatory-immune response without involvement of IL-6. The correlations between Ki67 and cytokines indicate the involvement of IL-8 and IL-10 in stimulation of cellular proliferation. IL-4 and IL-10 expression from CAL connective tissue simultaneously to IL-1, IL-4 and IL-10 inter-correlations there suggests the intensification of local immune response regulated probably by main pro-inflammatory cytokine-IL-1.
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    Characterization of SHH, SOX3, WNT3A and WNT9B Proteins in Human Non-Syndromic Cleft Lip and Palate Tissue
    (2023-06-09) Vaivads, Mārtiņš; Akota, Ilze; Pilmane, Māra; Institute of Anatomy and Anthropology; Department of Oral and Maxillofacial Surgery and Oral Medicine
    Orofacial clefts have been associated with specific cleft candidate genes which encode regulatory proteins required for orofacial region development. Cleft candidate genes encode proteins involved with the cleft morphopathogenesis process, but their exact interactions and roles are relatively unclear in human cleft tissue. This study evaluates the presence and correlations of Sonic Hedgehog (SHH), SRY-Box Transcription Factor 3 (SOX3), Wingless-type Family Member 3A (WNT3A) and 9B (WNT9B) protein containing cells in different cleft tissue. Non-syndromic cleft-affected tissue was subdivided into three groups—unilateral cleft lip (UCL) (n = 36), bilateral cleft lip (BCL) (n = 13), cleft palate (CP) (n = 26). Control tissue was obtained from five individuals. Immunohistochemistry was implemented. The semi-quantitative method was used. Non-parametric statistical methods were applied. A significant decrease in SHH was found in BCL and CP tissue. SOX3, WNT3A and WNT9B had a significant decrease in all clefts. Statistically significant correlations were found. The significant decrease in SHH could be associated with BCL and CP pathogenesis. SOX3, WNT3A and WNT9B could have morphopathogenetic involvement in UCL, BCL, and CP. Similar correlations imply the presence of similar pathogenetic mechanisms in different cleft variations.
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    Cleft Candidate Genes and Their Products in Human Unilateral Cleft Lip Tissue
    (2021-06) Vaivads, Mārtiņš; Akota, Ilze; Pilmane, Māra; Institute of Anatomy and Anthropology; Department of Oral and Maxillofacial Surgery and Oral Medicine
    Cleft lip and palate are common congenital pathologies that affect the human population worldwide. The formation of cleft lip is associated with multiple genes and their coded proteins, which regulate the development of craniofacial region, but the exact role of these factors is not always clear. The use of morphological studies for evaluation of human cleft-affected tissue has been limited because of insufficiency of available pathological material. The aim of this study was to detect and compare the immunohistochemical expression of cleft candidate gene coded proteins (DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, and FOXE1) in the non-syndromic unilateral cleft lip patient tissue and control group tissue. A semiquantitative counting method was used to evaluate the tissue in biotin-streptavidin-stained slides. Statistically significant differences between the patient and control groups were found for the number of immunoreactive structures for SHH (p = 0.019) and FOXE1 (p = 0.011) in the connective tissue and SOX3 (p = 0.012) in the epithelium. Multiple statistically significant very strong and strong correlations were found between the immunoreactives in cleft-affected tissue. These significant differences and various correlations indicate that multiple morphopathogenetic pathways are possibly involved in unilateral cleft lip pathogenesis. Therefore, we further discuss these possible interactions.
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    Cleft-related nose deformation evaluation and measurement methods. Literature review
    (2015) Bāgante, Ieva; Akota, Ilze; Rīga Stradiņš University
    INTRODUCTION: Rhinoplasty for the cleft lip and palate patient is very challenging and surgical outcome of the nose is difficult to evaluate. Discussions of aesthetic evaluation of the nose in cleft lip and palate patients remain problematical. Many different nose aesthetic evaluation methods have been described in the literature; they differ even among articles published in a single year. AIM: To analyse the literature concerning aesthetic evaluation of the nose in cleft lip and palate patients and to identify the most objective method for such evaluation postoperatively. MATERIAL AND METHODS: The literature was reviewed using MedLine and PubMed sources dated between January 1996 and December 2014. In total, 118 full text articles in English language were selected. Exclusion criteria were: case reports, surgical reviews, literature review, and single evaluations of nasal function. RESULTS: Measurements were obtained from two-dimensional images in 73 articles. Noses were evaluated from 3D images in 22 and by clinical examination in 15. Other methods were evaluation from dental/facial casts, cephalometric evaluation, computer tomography and video recording. In 26 articles some combination of methods was used. CONCLUSIONS: The most popular evaluation method is still two-dimensional photography and measurements using anthropometric facial landmarks. Measurements from three-dimensional images seem to be the most objective method and automated facial anthropometric landmark protraction seems to hold promise for the future.
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    COVID-19 : The immediate response of european academic dental institutions and future implications for dental education
    (2020-11-01) Quinn, Barry; Field, James; Gorter, Ronald; Akota, Ilze; Manzanares, Maria Cristina; Paganelli, Corrado; Davies, Julia; Dixon, Jonathan; Gabor, Gerber; Amaral Mendes, Rui; Hahn, Petra; Vital, Sibylle; O’Brien, Judith; Murphy, Denis; Tubert-Jeannin, Stéphanie; Rīga Stradiņš University
    The COVID-19 pandemic has had an immediate and dramatic impact on dental education. The Association of Dental Education in Europe decided to carry out an investigation to assess the immediate response of European Academic Dental Institutions. An online survey was sent to both member and non-member dental schools to investigate the impact on non-clinical and clinical education, assessment and the well-being/pastoral care measures implemented. The preliminary findings and discussion are presented in this paper, for the responses collected between the 25 March and 5 April 2020. The survey at this time of publication is ongoing, and detailed results can be accessed https://adee.org/covid-19-european-dental-education%E2%80%99s-immediate-response.
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    Craniofacial Morphology in the Parents of Children with Cleft Lip, Cleft Lip and Palate and Isolated Cleft Palate. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2011) Mauliņa, Ieva; Akota, Ilze
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    Deguna elpošanas funkcija un estētika bērniem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2018) Bāgante, Ieva; Akota, Ilze
    Lūpu un aukslēju šķeltnes ir biežākā iedzimtā patoloģija sejas un žokļu rajonā. Vienpusējas caurejošas lūpas, alveolārā izauguma un aukslēju šķeltnes gadījumā vienmēr novēro tipisku deguna deformāciju. Tā kā deguns ir novietots sejas centrālajā daļā, tā izskatam ir ievērojama ietekme kopējā sejas estētikā. Pētījumi par iedzimtām sejas šķeltnēm joprojām ir aktuāli, jo nav vienotas pieejas par šādu deformāciju korekcijas laikiem un metodiku, lai panāktu gan labu funkcionālu, gan estētisku rezultātu. Arī diskusijas par deguna estētikas novērtēšanas metodēm pacientiem ar lūpu un aukslēju šķeltnēm joprojām ir aktuālas. Deguna estētikas objektīvai un kvantitatīvai novērtēšanai līdz šim nav aprakstītas vispāratzītas metodes. Tāpat nav noteikti vispāratzīti mērāmie parametri, pēc kuriem noteikt deguna estētiku. Lai varētu novērtēt deguna un augšlūpas estētiku un deguna elpošanas funkciju bērniem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni, nepieciešamas objektīvas un ērti lietojamas metodes, ar kurām varētu kvalitatīvi un kvantitatīvi noteikt ārstēšanas rezultātus. Pētījumā veikta detalizēta literatūras avotu analīze par deguna estētikas novērtēšanas metodēm, apkopojot to pozitīvos un negatīvos aspektus. Literatūrā visbiežāk deguna estētika tika noteikta divdimensiju (2D) fotoattēlos. Pētījuma pirmajā daļā tika iekļauti 27 bērnu 2D fotoattēli deguna estētikas noteikšanai ar modificētu Anastassov un Chipkov (2003) detalizēto vērtēšanas skalu un vizuālo analogu skalu. Līdz šim šāda detalizēta deguna estētikas novērtēšanas skala mērījumiem 2D fotoattēlos literatūrā nav bijusi aprakstīta. Pēc datu statistiskās apstrādes konkrētajai pētījuma grupai varēja secināt, ka izvēlētās metodes objektivitāte nebija pārliecinoša. Pētījuma otrajā daļā deguna simetrijas novērtēšanai tika izmantoti trīsdimensiju (3D) fotoattēli ar antropometrisko punktu atlikšanu. Literatūras dati liecināja, ka deguna simetrijas mērījumi 3D fotoattēlos ir bijuši objektīvi. Pētījuma otrajā daļā tika iekļauti 35 bērni ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni un tika izmantota inovatīva aparatūra un metode deguna un augšlūpas simetrijas novērtēšanai 3D fotoattēlos un deguna elpošanas funkcijas noteikšana ar priekšēju rinomanometriju, salīdzinot ar kontroles grupu. Rezultātā deguna anatomiskā forma pēc plastiskajām vienpusējas caurejošas lūpas, alveolārā izauguma un aukslēju šķeltnes operācijām bija atjaunota, tomēr deguna simetrija pētījuma grupā atšķīrās no kontroles grupas. Pacientiem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni pēc rinoplastikas elpošanas plūsma caur veselo pusi bija labāka nekā caur šķeltnes pusi. Kontroles grupā elpošana bija labāka nekā pacientiem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni. Deguna simetrijas novērtējums 3D fotoattēlos ar detalizētiem antropometriskiem mērījumiem bija kvalitatīvi un kvantitatīvi vērtējams, bet deguna estētikas novērtējums 2D fotoattēlos ar izvēlētajām novērtēšanas metodēm uzrādīja subjektīvus rezultātus. Deguna simetrijas noteikšanai rekomendējams izmantot 3D fotoattēlus ar izvēlētajiem antropometriskajiem punktiem. Šajā pētījumā lietotie antropometriskie punkti un attālumi deguna un augšlūpas simetrijas noteikšanai rekomendējami lietot klīnikā rutīnā. Rinomanometriju ieteicams veikt kā rutīnas izmeklējumu pirms un pēc deguna ķirurģiskas ārstēšanas.
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    Deguna elpošanas funkcija un estētika bērniem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni. Promocijas darbs
    (Rīgas Stradiņa universitāte, 2018) Bāgante, Ieva; Akota, Ilze
    Lūpu un aukslēju šķeltnes ir biežākā iedzimtā patoloģija sejas un žokļu rajonā. Vienpusējas caurejošas lūpas, alveolārā izauguma un aukslēju šķeltnes gadījumā vienmēr novēro tipisku deguna deformāciju. Tā kā deguns ir novietots sejas centrālajā daļā, tā izskatam ir ievērojama ietekme kopējā sejas estētikā. Pētījumi par iedzimtām sejas šķeltnēm joprojām ir aktuāli, jo nav vienotas pieejas par šādu deformāciju korekcijas laikiem un metodiku, lai panāktu gan labu funkcionālu, gan estētisku rezultātu. Arī diskusijas par deguna estētikas novērtēšanas metodēm pacientiem ar lūpu un aukslēju šķeltnēm joprojām ir aktuālas. Deguna estētikas objektīvai un kvantitatīvai novērtēšanai līdz šim nav aprakstītas vispāratzītas metodes. Tāpat nav noteikti vispāratzīti mērāmie parametri, pēc kuriem noteikt deguna estētiku. Lai varētu novērtēt deguna un augšlūpas estētiku un deguna elpošanas funkciju bērniem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni, nepieciešamas objektīvas un ērti lietojamas metodes, ar kurām varētu kvalitatīvi un kvantitatīvi noteikt ārstēšanas rezultātus. Pētījumā veikta detalizēta literatūras avotu analīze par deguna estētikas novērtēšanas metodēm, apkopojot to pozitīvos un negatīvos aspektus. Literatūrā visbiežāk deguna estētika tika noteikta divdimensiju (2D) fotoattēlos. Pētījuma pirmajā daļā tika iekļauti 27 bērnu 2D fotoattēli deguna estētikas noteikšanai ar modificētu Anastassov un Chipkov (2003) detalizēto vērtēšanas skalu un vizuālo analogu skalu. Līdz šim šāda detalizēta deguna estētikas novērtēšanas skala mērījumiem 2D fotoattēlos literatūrā nav bijusi aprakstīta. Pēc datu statistiskās apstrādes konkrētajai pētījuma grupai varēja secināt, ka izvēlētās metodes objektivitāte nebija pārliecinoša. Pētījuma otrajā daļā deguna simetrijas novērtēšanai tika izmantoti trīsdimensiju (3D) fotoattēli ar antropometrisko punktu atlikšanu. Literatūras dati liecināja, ka deguna simetrijas mērījumi 3D fotoattēlos ir bijuši objektīvi. Pētījuma otrajā daļā tika iekļauti 35 bērni ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni un tika izmantota inovatīva aparatūra un metode deguna un augšlūpas simetrijas novērtēšanai 3D fotoattēlos un deguna elpošanas funkcijas noteikšana ar priekšēju rinomanometriju, salīdzinot ar kontroles grupu. Rezultātā deguna anatomiskā forma pēc plastiskajām vienpusējas caurejošas lūpas, alveolārā izauguma un aukslēju šķeltnes operācijām bija atjaunota, tomēr deguna simetrija pētījuma grupā atšķīrās no kontroles grupas. Pacientiem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni pēc rinoplastikas elpošanas plūsma caur veselo pusi bija labāka nekā caur šķeltnes pusi. Kontroles grupā elpošana bija labāka nekā pacientiem ar vienpusēju caurejošu lūpas, alveolārā izauguma un aukslēju šķeltni. Deguna simetrijas novērtējums 3D fotoattēlos ar detalizētiem antropometriskiem mērījumiem bija kvalitatīvi un kvantitatīvi vērtējams, bet deguna estētikas novērtējums 2D fotoattēlos ar izvēlētajām novērtēšanas metodēm uzrādīja subjektīvus rezultātus. Deguna simetrijas noteikšanai rekomendējams izmantot 3D fotoattēlus ar izvēlētajiem antropometriskajiem punktiem. Šajā pētījumā lietotie antropometriskie punkti un attālumi deguna un augšlūpas simetrijas noteikšanai rekomendējami lietot klīnikā rutīnā. Rinomanometriju ieteicams veikt kā rutīnas izmeklējumu pirms un pēc deguna ķirurģiskas ārstēšanas.
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    Dental Anomalies and Oral Health in Children with Nonsyndromic Clefts in Latvian Population and Their Association with Genetic Changes. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2017) Kadiķe, Kristīne; Care, Rūta; Akota, Ilze
    Cleft lip and palate is one of the most common congenital malformation in maxillofacial region. The etiology of clefts are complex, involving both genetic and environmental factors. Dental anomalies in children with congenital clefts occure more often, they are considered as an additional clinical marker for determining the risk of clefts. One of the most common oral disease is dental caries. There is increasing research into genetics relating to dental caries and genes involved in caries susceptibility. The aim of this study is to investigate the types of dental anomalies and determine the oral health status of children with nonsyndromic congenital clefts in Latvia and their association with genetic markers rs2240308, rs11867417, rs9929218, rs642961, rs11362, rs1800972. This study is important as it has provided novel data about dental anomalies and oral health in children with nonsyndromic congenital clefts in Latvia as well as studied specific genetic markers in association with both dental anomalies and dental caries. The study consisted of three parts; the first, a retrospective analysis of 126 clinical charts for children with nonsyndromic clefts. It shoved that more dental anomalies were seen in children with bilateral (87.5%) and unilateral (75%) cleft lip and palate. The most common dental anomalies werehypodontia (29.37%) and microdontia(28.57%). The second part was the assesment of oral health evaluating the presence of dental caries, plaque and gum bleeding. Oral health was evaluated in 171 children with nonsyndromic clefts. This was compared to the control group of 196 children inthree different age groups (2 – 3, 6 – 7 and 11 – 12 year olds) according to the bite development. Overall, the prevalence of caries in cleft group children was lower compared to the control group. Caries intensity of 2 – 3 year old children with clefts was lower (dmf=3.49) compared to control group (4.78). In the 6 – 7 year old group caries intensity was higher and more filled teeth were present in the cleft group. In the 11 – 12 year old group caries intensity was similar in both groups. The plaque and bleeding index in both cleft and control groups was similar, except for plaque index in the 2 – 3 year old children and bleeding index in the 6 – 7 year old group which was less in the cleft group compared to the control group. When assessing oral health influencing behavioural factors using parental questionnaires, no specific factors were identified. The third part of this study was the identification of genetic markers associated with both, dental anomalies (rs2240308, rs11867417, rs9929218, rs642961), and dental caries (rs11362, rs1800972).The research identifiedIRF6(Interferon Regulatory Factor 6) genegenetic markers rs642961 significant association with dental anomalies and nonsyndromic clefts.This marker’s A allele was particularly associated with an increased risk of clefts. DEFB1(Defensin beta 1) gene genetic markers rs11362 studies identified association with caries in children with nonsyndromic clefts. In addition this gene’s expression in the oral cavity may be associated with an individual’s susceptibility to the dental caries. The results of this study provides insight in this complex multifactorial pathology and the role of possible genes involved. A multidisciplinary approach between health professionals from Cleft lip and palate centres and other professionals involved in the care is essential in order to improve care for the children with congenital nonsyndromic clefts.
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    Evaluation of the multiple tissue factors in bone of primary osteoplasty and rhinoplasty in patients affected by cleft lip palate
    (2022-07) Buile, Dace; Pilmane, Māra; Akota, Ilze; Department of Morphology; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    Clefts of the lip and/or palate (CLP) are visible disruptions of standard facial structure. The aim of our study was to determine a relative number and appearance of the tissue factors in bone of patients with CLP during first time plastic alveolar osteoplasty or rhinoplasty. Immunohistochemistry was performed with matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), osteopontin (OPN), osteocalcin (OC), Runt-related transcription factor 2 (Runx2), beta-defensin-2 (βdef-2), beta-defensin-3 (βdef-3), interleukin-1 alpha (IL-1α), and interleukin-10 (IL-10). The bone formation was observed by Masson-trichrome (Masson) staining. For the quantification of structures, the semi-quantitative census method was used. Spearman rank order correlation coefficient and Mann-Whitney U test were used for the statistical analysis. A significantly higher number of OPN positive osteocytes was observed in the CLP group when compared to the control group (p=0.002). The number of OC positive osteocytes (p=0.000) and βdef-2 positive osteocytes (p=0.003) was significantly lower in the CLP group in comparison to the control group. Strong, positive correlations between IL-10 and OC (rs=0.608; p=0.002), IL-1α and MMP-9 (rs=0.666; p=0.000), OPN and MMP-8 (rs=0.620; p=0.002) were detected in the CLP group. A tendency for the increased appearance of MMP-8, MMP-9 positive osteocytes of the patients with CLP, suggests elevated tissue remodelling properties. Increased appearance of OPN positive osteocytes in bone of the patients with CLP shows increased bone homeostasis based on seriously decreased mineralization, which may be a possible compensatory reaction to decreased quality of postsurgical bone.
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    Evaluation of the Multiple Tissue Factors in the Cartilage of Primary and Secondary Rhinoplasty in Cleft Lip and Palate Patients
    (2022-10-02) Buile, Dace; Pilmane, Māra; Akota, Ilze; Department of Morphology; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    Cleft lip and palate (CLP) is one of the craniofacial defects. The objective of this study was to identify the differences in appearance between the tissue factors in cartilage of CLP patients after primary and secondary rhinoplasty. Immunohistochemistry was performed with MMP-2, MMP-8, MMP-9, TIMP-2, IL-1α, IL-10, bFGF, and TGFβ1. The quantification of the structures was performed using a semi-quantitative census method. MMP-2, -9, IL-1a, and bFGF demonstrated higher number of positive cells in patients, while the number of MMP-8, IL-1a, -10 and TGFβ1 cells was higher or equal in the control subjects. The only statistically significant difference between CLP-operated patients was found in the TIMP-2 group, where the primary CLP patient group had a higher number of TIMP-2 positive chondrocytes than the secondary CLP patient group (U = 53.5; p = 0.021). The median value of the primary CLP group was ++ number of TIMP-2 positive chondrocytes compared to +++ in the secondary CLP group. No statistically significant difference was found between primary and secondary rhinoplasty patients for other tissue factors. Commonly, the rich expression of different tissue factors suggests a stimulation of higher elasticity in cleft affected cartilage. The statistically significant TIMP-2 elevation in primary operated cartilage indicates an impact of the selective tissue remodeling for hard tissue.
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    Expression of gene proteins, interleukins and β-defensin in cleft-affected tissue
    (2017) Jankovska, Iveta; Pilmane, Mara; Akota, Ilze; Rīga Stradiņš University; Department of Morphology; Institute of Anatomy and Anthropology
    OBJECTIVES: The aim of the study was to investigate cleft - affected tissues in children with cleft lip and palate in order to detect appearance of β-defensin, interleukins (IL) and gene proteins. MATERIAL AND METHODS: The study group included 10 patients with cleft lip and palate. During nose surgery tissue samples from bone and cartilage have been taken, and stained with immunohistochemistry for β-defensin 2, IL4, IL6, IL7, IL8, IL10 and MSX1, RYK, PAX9, IRF6 gene proteins. RESULTS: Results showed prominent expression of IL10 (mean value 47.28±4.26 in visual field) followed by IL7 (35.62±11.18) in cartilage of patients, but slightly less pronounced expression of IL8 (30.14±8.74), IL6 (22.52±10.88) and IL4 (14.81±6.94). The expression of β-defensin 2 was prominent (34.52±11.79) and similar to expression of IL7 in tissue samples of cartilage. MSX1, PAX9, RYK and IRF6 (17.67±5.94; 16.14±5.52; 16.57±5.22 and 11.86±4.21) in cartilage was less pronounced than interleukins and β-defensin 2. MSX1 (12.44±3.34), PAX9 (6.89±2.14), RYK (11.0±5.92) and IRF6 (9.1±4.76) gene proteins expression in bone showed mostly rare occurrence of positive structures. CONCLUSIONS: Significant expression of IL7 and β-defensin 2 and IL10 in cartilage proves the prominent immune response in cleft affected hard tissue. Mostly indistinct MSX1, PAX9, RYK and IRF6 gene proteins expression in bone might be an indicator of not complete cellular differentiation, proliferation and migration events in cleft disordered hard tissue.
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    Expression of Gene Runx2, Wnt and OPG in Palate Cleft Reconstruction Material
    (2018) Šmitiņš, Emīls; Danberga, Dace; Pilmane, Māra; Akota, Ilze; Institute of Anatomy and Anthropology; Rīga Stradiņš University
    Introduction. Facial morphogenesis occurs from the fourth to the twelfth gestation week, when the cells from nerve crest migrate to the region of face, forming the primary palate. The cleft palate is an abnormality in embryogenesis period, which is characterized by the absence of fusion of palatal shelves. The incidence of cleft lip and palate is one in 700 live births. In recent years the effect of different genes and signaling molecules, including Runx2, Wnt3 and OPG have been studied in the development of cleft palate, because these substances are considered to be regulators of pathogenesis responsible for formation of bone and cartilage tissue and particularly the bone. Aim of the Study. The aim of the work was to evaluate the expression of Runx2, Wnt3 and OPG in palate bone and nasal cartilage for children with cleft palate. Material and methods. Eleven bone and cartilage samples were obtained from 21 children of the lip, soft and hard palate correction surgery. All the patients were diagnosed with clefts of the lip, alveolar process of maxilla, and palate. In the tissue sections using the immunohistochemistry method (IMH), were determined Runx2 (code: AB192256, 1: 250, Abcam GB, rabbit), Wnt3 (code: AB1992, 1: 800, Abcam GB, rabbit), and OPG (code: A0611, 1: 100, The Orbit USA, rabbit) local expression. We used a semi-quantitative census method for quantifying the positive structures. Results. Runx2 expression was observed in five patient bone tissue samples and six patient cartilage tissue samples. Of the Runx2 positive bone tissue, in one case we observed occasional, in two cases- few, in one case- moderate to numerous and in one case numerous positive osteocytes while in tissue of cartilage in two cases we observed few, in one case- few to moderate, in two cases moderate, and in one case numerous positive chondrocytes. A significant difference in Wnt3 expiation was observed between bone and cartilage tissues. Wnt3 expressing chondrocytes were observed in all samples, where in one case- occasional, in three cases few, in one case-moderate, and in six cases-numerous positive cartilage cells were observed. The expression of the gene in the bone was observed in nine cases, which contained mostly occasional or few positive structures, except in three cases where in one Wnt3 was marked by few to moderate and in two cases numerous positive osteocytes. OPG expression was observed in all samples, but in the cartilage, the expression was more pronounced. In the cartilage in seven cases, there were numerous positive chondrocytes, in one case- few to moderate, in two cases moderate to numerous and in one case few to moderate number of chondrocytes. OPG showed variable expression. In four cases, we observed occasional to few, in one case few to moderate, in one case- moderate, in one case moderate to numerous and in four cases numerous positive bone cells. Conclusion. Cartilage tissue expresses significantly more Runx2, Wnt3 genes and OPG proteins, indicating a greater compensatory tissue capacity. In the case of palate clefts, the high expression of Wnt3 and OPG and lower expression of Runx2 could indicate a significant tissue proliferation which predominates over mineralization and ossification processes.
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    Expression of growth factors and growth factor receptors in human cleft-affected tissue
    (2013) Krivicka, Benita; Pilmane, Mara; Akota, Ilze; Institute of Anatomy and Anthropology; Department of Oral and Maxillofacial Surgery and Oral Medicine
    OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate and cleft lip with or without alveolar clefting for detection of local tissue growth factors and growth factor receptors and compare findings. Design. Morphological analysis of human tissue. Patients. Three groups were studied: 14 patients with cleft palate at the age from eight months to 18 years and two months, 12 patients with cleft lip with or without alveolar clefting in the age from four months to 15 years and four months and 11 control patients. RESULTS. In general, cleft palate disordered tissue showed more prominent expression of BMP2/4 (z=3.574; p=0.0004) and TGFβ (z=2.127; p=0.033), while expression of TGFBR3 significantly higher was only in connective tissue (z=3.822; p=0.0001). Cleft lip affected tissue showed significantly pronounced expression of FGFR1 in general as well as separately in epithelium. CONCLUSIONS. The marked and statistically significant expression of BMP 2/4 in cleft palate disordered soft tissue probably is delayed, but still proliferation and differentiation as well as tissue, especially, bone remodeling contributing signal. Cleft palate affected tissue show more prominent expression of TGFβ, still the weak regional expression of TGFβ type III receptors prove the disordered tissue growth and changed TGFβ signalling pathway in postnatal pathogenesis. In general, expression of TGFβ, BMP 2/4 and FGFR1 is significantly different, giving evidence to the involvement of these mentioned factors in the cleft severity morphopathogenesis.
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    Expression of TGFβ-3, PAX9, RYK, matrix metalloproteinases and their tissue inhibitors in human cleft-affected tissue
    (2015-07-07) Krivicka, Benita; Pilmane, Māra; Akota, Ilze; Institute of Anatomy and Anthropology; Department of Morphology; Rīga Stradiņš University
    Formation of mammalian lip and palate involves multiple developmental steps that finally lead to the fusion of the two bilateral palatal shelves along the facial midline. Recent studies confirm that on the basis successful orofacial formation is coordinated interactions of several factors including genes, growth factors, enzymes and their natural inhibitors. The aim of our study was to investigate cleft disordered tissue in children with cleft lip and palate for detection of local expression of key regulators of palatogenesis. The study involved 10 patients with unilateral cleft lip and palate at the age of three months to four years and eight months. Tissue samples were collected during the surgical procedure from the borders of the cleft region. Material was proceed for detection of PAX9, RYK, TGFβ-3, MMP-8, MMP-9 and TIMP-2 with biotin-streptavidin immunohistochemistry. Distribution of immunoreactive structures was detected semiquantitatively. Expression of PAX9 and RYK was more pronounced in cleft lip and palate disordered epithelium. The relative number of PAX9 positive epitheliocytes was very variable, while RYK mainly stained few cells localized into middle layers. Expression of TGFβ-3 was detected in the tissue of all patients. We saw numerous positive epitheliocytes in eight cases, but underlying connective tissue mainly demonstrated few or moderate number immunoreactive cells. Expression of MMP-8 was found only in epithelium of eight patients and it was slight, while MMP-9 and TIMP-2 marked variable number of positive epithelial and connective tissue cells. Conclusions. Expression of Pax-9 is more characteristic for cleft lip and palate affected tissue and probably facilitates tissue reconstruction due to its mitogenic effect. Rich expression of TGFβ-3 in cleft lip and palate disordered tissue may play a role in successful tissue remodelling and scar-free healing. Cleft lip and palate disordered tissue are characterizied by more pronounced expression of MMP-9, it slightly predominate expression of TIMP-2, giving evidence to the involvement of mentioned factors in the postnatal tissue remodeling.
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