Esta pesquisa teve como objetivo estudar in situ o efeito protetor de um gel à base de Cranberry aplicado sobre a dentina submetida à erosão. Este estudo duplo cego e cruzado constou de 2 fases com duração de 5 dias cada. Para tal, 10 voluntários utilizaram2 aparelhos palatinos (um em cada fase) com 4 blocos de dentina bovina divididos em 2 grupos. Na primeira fase estiveram presentes os grupos: G1 Ação da bebida ácida (Coca-cola®) sobre a dentina bovina sem nenhum tipo de tratamento prévio; G2 - Ação da bebida ácida sobre a dentina tratada com gel à base de Cranberry e na segunda fase foi testado os grupos: G3 Ação da bebida sobre a dentina tratada com gel de aplicação tópica sem nenhum princípio ativo; G4 - Ação da bebida ácida sobre a dentina tratada previamente com gel de Clorexidina. Cada aparelho foi imerso na bebida ácida, 3x/dia, durante 5 minutos por 5 dias. A porcentagem de perda de microdureza de superfície (%PDS) e a perfilometria foram as variáveis utilizadas para quantificar as alterações dadentina. A comparação dos grupos por meio da análise de variância de medidas repetidas seguido do teste de Fisher mostrou haver diferenças estatisticamente significativas entre os grupos para o desgaste (G1: 4,98 μm ± 1,36; G2: 3,29 μm ± 1,16; G3: 4,38 μm ± 1,19; G4: 3,32 μm ± 1,55) e não apresentou diferenças entre eles na %PDS (G1: 28,12 ± 5,71; G2: 24,92 ± 5,38; G3: 25,74 ± 9,15; G4: 29,83 ± 8,63).Assim, quanto ao desgaste não houve diferença estatisticamente significativa entre os grupos controle e placebo, também não houve uma diferença entre os grupos Cranberry e clorexidina. Porém, os grupos Cranberry e clorexidina apresentaram menores valores de desgaste em relação aos grupos Placebo e Controle (sem gel), sendo esta diferença estatisticamente significativa. Os resultados obtidos nesse estudo sugerem uma significativa eficácia dos géis ativos à base de Cranberry e de Clorexidina na prevenção do desgaste da dentina submetida à erosão dentária. / The aim of this study is to evaluate the in situ effect of a Cranberry gel over dentine submitted to a erosive challenge. This crossover doble-blinded study was performed in 2 phases of 5 days each. For that purpose, 10 volunteers wore 2 palatal devices (1 for each phase) with 4 dentin specimens divided into 2 groups: First Phase: G1 - Erosive challenge (Coca-cola®) over dentine without any previous treatment; G2 - Erosive challenge over dentine previously treated with Cranberry gel; and Second Phase: G3 - Erosive challenge over dentine previously treated with a gel withot any active principle; G4 - Erosive challenge over dentine previously treated with Clorexidine gel. Each device was immersed into the acid beverage, 3 times daily for 5 minutes during 5 days. The surface microhardness change percentage (%SMC) and profilometry were be used to quantify the dentin alteratons. The comparison between groups by repeated measures analysis of variance followed by Fisher\'s test showed statistically significant differences between groups for wear (G1: 4.98 ± 1.36 mM, G2: 3.29 ± 1 mM, 16, G3: 4.38 ± 1.19 mM; G4: 3.32 ± 1.55 mM) and showed no differences b in% SMH (G1: 28.12 ± 5.71; G2: 24.92 ± 5.38, G3: 25.74 ± 9.15; G4: 29,83 ± 8,63). So as to wear there was no statistically significant difference between the placebo and control groups.There was also no difference between Cranberry andchlorhexidine groups. However, Cranberry and chlorhexidine groups presented lower wear compared to placebo and control groups (without gel), and this difference was statistically significant. The results of this study suggest a significant efficacy of active gels based Cranberry and chlorhexidine in preventing wear of dentin subjected to dental erosion.

O processo de reparo do tecido ósseo tem sido alvo de estudos com o intuito de promover uma melhora na qualidade e tempo de reparo. Um elemento que tem sido estudado por alguns grupos é o fluoreto, pois tem sido proposto como terapêutico para osteoporose (Europa). Deste modo, o objetivo deste trabalho foi avaliar comparativamente o efeito do fluoreto administrado na água de beber sobre o reparo ósseo alveolar de ratos. Neste estudo foram utilizados 4 grupos com ratos Wistar de 80 dias de vida (n=200), os quais receberam água de beber contendo 5, 15 e 50 ppm de fluoreto e água deionizada (controle) durante todo experimento. Esses animais tiveram o incisivo superior direito extraído. Os animais foram eutanasiados 0 hora, 7, 14, 21 e 30 e 60 dias após a extração. Amostras de plasma sanguíneo foram obtidas para análise de concentração de flúor, e a região do alvéolo dental foi coletada para as análises de microscopia (Hematoxilina Eosina e imunoistoquímica) e zimografia (metaloproteinases de matriz 2 e 9 MMP-2 e 9). A análise de concentração de flúor no plasma sangüíneo mostrou maior presença desse elemento no grupo tratado com 50 ppm de F nos períodos de 21 e 30 dias. Na análise histológica foi detectado osso neoformado em todos os animais até 60 dias, porém o grupo de 50 ppm de F apresentou menor formação óssea nos períodos de 14, 21 e 30dias. A análise morfométrica confirmou um aumento na densidade de volume de osso neoformado, entre 7 e 60 dias, nos grupos controle, 5 ppm, 15 ppm e 50 ppm de F, com concomitante diminuição na densidade de volume de coágulo sangüíneo. A expressão de RANK-L e OPG não foi alterada pela exposição crônica ao fluoreto na água de beber durante os períodos estudados (p<0,05). A atividade da MMP-2 foi mais acentuada no período inicial, enquanto a MMP-9 teve maior atividade no período final. Concluiu-se que o F, em altas concentrações pode alterar a dinâmica do reparo ósseo alveolar diminuindo a formação de novo tecido ósseo, associado a um atraso na remissão do coágulo sangüíneo. Proteínas como RANK-L, OPG, MMP-2 e MMP-9 também podem ter sua expressão alterada no tecido ósseo em reparo. / The repair of bone has been investigated with the aim of promoting an improvement in the quality and time of the repair process. One element that has been studied by some groups is fluoride, it has been proposed as a treatment for osteoporosis (Europe). Thus, the objective was to comparatively evaluate the effect of fluoride administered in drinking water on alveolar bone repair in rats. This study used 4 groups of rats of 80 days (n=200), which received drinking water containing 5, 15, and 50 ppm of fluoride, and deionized water (control) throughout the experiment. These animals had their upper right incisor extracted. The animals were euthanized 0 hours, 7, 14, 21 and 30 and 60 days after extraction. Samples of blood plasma were obtained for analysis of fluoride concentration, and the region of the alveolus was collected for microscopic analysis (Hematoxylin eosin and Immunohistochemistry) and zymography (metalloproteinases 2 and 9 MMP-2 and 9). Analysis of fluoride concentration in blood plasma showed a greater presence of this element in the group treated with 50 ppm of F in periods of 21 and 30 days. Histological analysis detected a new bone formed in all animals up to 60 days, but the group of 50 ppm F showed lower bone formation at 14, 21 and 30 days. Morphometric analysis confirmed an increase in the volume density of newly formed bone, between 7 and 60 days in control groups, 5 ppm, 15 ppm and 50 ppm F, with a concomitant decrease in the volume density of blood clot. The expression of RANK-L and OPG was not altered by chronic exposure to fluoride in drinking water during the study period (p<0.05). The activity of MMP-2 was more pronounced in the early period, while MMP-9 had higher activity in the final period. It was conclude that the F, in high concentrations change the dynamics of the alveolar bone repair by decreasing the formation of new bone, associated with a delay in treating the blood clot. Proteins as RNK-L, OPG, MMP-2 and MMP-9 may also have changed in their expression in bone tissue repair.

Esta pesquisa teve como objetivo estudar in situ o efeito protetor de um gel à base de Cranberry aplicado sobre a dentina submetida à erosão. Este estudo duplo cego e cruzado constou de 2 fases com duração de 5 dias cada. Para tal, 10 voluntários utilizaram2 aparelhos palatinos (um em cada fase) com 4 blocos de dentina bovina divididos em 2 grupos. Na primeira fase estiveram presentes os grupos: G1 Ação da bebida ácida (Coca-cola®) sobre a dentina bovina sem nenhum tipo de tratamento prévio; G2 - Ação da bebida ácida sobre a dentina tratada com gel à base de Cranberry e na segunda fase foi testado os grupos: G3 Ação da bebida sobre a dentina tratada com gel de aplicação tópica sem nenhum princípio ativo; G4 - Ação da bebida ácida sobre a dentina tratada previamente com gel de Clorexidina. Cada aparelho foi imerso na bebida ácida, 3x/dia, durante 5 minutos por 5 dias. A porcentagem de perda de microdureza de superfície (%PDS) e a perfilometria foram as variáveis utilizadas para quantificar as alterações dadentina. A comparação dos grupos por meio da análise de variância de medidas repetidas seguido do teste de Fisher mostrou haver diferenças estatisticamente significativas entre os grupos para o desgaste (G1: 4,98 &#x3BC;m ± 1,36; G2: 3,29 &#x3BC;m ± 1,16; G3: 4,38 &#x3BC;m ± 1,19; G4: 3,32 &#x3BC;m ± 1,55) e não apresentou diferenças entre eles na %PDS (G1: 28,12 ± 5,71; G2: 24,92 ± 5,38; G3: 25,74 ± 9,15; G4: 29,83 ± 8,63).Assim, quanto ao desgaste não houve diferença estatisticamente significativa entre os grupos controle e placebo, também não houve uma diferença entre os grupos Cranberry e clorexidina. Porém, os grupos Cranberry e clorexidina apresentaram menores valores de desgaste em relação aos grupos Placebo e Controle (sem gel), sendo esta diferença estatisticamente significativa. Os resultados obtidos nesse estudo sugerem uma significativa eficácia dos géis ativos à base de Cranberry e de Clorexidina na prevenção do desgaste da dentina submetida à erosão dentária. / The aim of this study is to evaluate the in situ effect of a Cranberry gel over dentine submitted to a erosive challenge. This crossover doble-blinded study was performed in 2 phases of 5 days each. For that purpose, 10 volunteers wore 2 palatal devices (1 for each phase) with 4 dentin specimens divided into 2 groups: First Phase: G1 - Erosive challenge (Coca-cola®) over dentine without any previous treatment; G2 - Erosive challenge over dentine previously treated with Cranberry gel; and Second Phase: G3 - Erosive challenge over dentine previously treated with a gel withot any active principle; G4 - Erosive challenge over dentine previously treated with Clorexidine gel. Each device was immersed into the acid beverage, 3 times daily for 5 minutes during 5 days. The surface microhardness change percentage (%SMC) and profilometry were be used to quantify the dentin alteratons. The comparison between groups by repeated measures analysis of variance followed by Fisher\'s test showed statistically significant differences between groups for wear (G1: 4.98 ± 1.36 mM, G2: 3.29 ± 1 mM, 16, G3: 4.38 ± 1.19 mM; G4: 3.32 ± 1.55 mM) and showed no differences b in% SMH (G1: 28.12 ± 5.71; G2: 24.92 ± 5.38, G3: 25.74 ± 9.15; G4: 29,83 ± 8,63). So as to wear there was no statistically significant difference between the placebo and control groups.There was also no difference between Cranberry andchlorhexidine groups. However, Cranberry and chlorhexidine groups presented lower wear compared to placebo and control groups (without gel), and this difference was statistically significant. The results of this study suggest a significant efficacy of active gels based Cranberry and chlorhexidine in preventing wear of dentin subjected to dental erosion.

Background: Matrix metalloproteinases (MMPs) have been shown to be involved in cancers and atherosclerosis, the leading causes of present day mortality. The objectives of the cancer element of this project were to investigate single nucleotide polymorphisms (SNPs) in MMP1 and MMP8 regarding breast cancer and malignant melanoma, and a functional characterisation of the genetic variants, including the MMP1 polymorphism rs19799750, previously associated with multiple cancers. The objective of the second part of this project was to investigate whether MMP8 played a role in the development of atherosclerotic lesions and if so, the underlying mechanisms. Methods/Results: Genetic investigations found the MMP8 SNP rs11225395 to be associated with the occurrence of both breast cancer and malignant melanoma; furthermore it was also associated with reduced lymph node metastasis, reduced cancer relapse and greater survival. Functional luciferase assays showed that the minor allele of the polymorphism has higher promoter activity in breast cancer and melanoma cell lines. They also showed haplotypic effects on MMP1 promoter activity in several cancer cell lines by the 2G allele of polymorphism rs1799750 and one or more MMP1 promoter SNPS. The second part of the study found an association between a MMP8 SNP and the extent of coronary atherosclerosis; additionally a relationship among MMP8 gene variation, plasma VCAM-1 level, and atherosclerosis progression was observed in a prospective study. Murine studies showed reduced atherosclerosis in MMP8/ApoE knockout mice compared with ApoE knockout littermate controls. Biochemical studies confirmed that MMP8 can convert angiotensin I to angiotensin II. Conclusions: The data of the first part of this project support the notion that genetic polymorphisms in the MMP1 and MMP8 influence the expression of these genes and the development and progression of cancer. The results of the second part of this project indicate an important role of MMP8 in the pathogenesis of atherosclerosis.

Matrix metalloproteinases (MMPs) are required for tissue remodelling processes, including angiogenesis. MMP activity is generally proangiogenic but MMP-12 is suggested to be antiangiogenic and its precise role is still unclear. The work in this thesis describes the synthesis of an MMP-12 inhibitor and activity probe to address the hypothesis that MMP-12 inhibits angiogenesis. An inhibitor, synthesised in-house, selectively inhibited MMP-12 in in vitro recombinant enzyme assays. An activity probe, also synthesised in-house, was selective for MMP-12 in in vitro recombinant enzyme assays. The function of MMP-12 during angiogenesis was assessed using murine models of angiogenesis; the in vivo sponge implantation, and the ex vivo aortic ring assays. Angiogenesis and MMP activity were imaged in vivo in sponges in C57Bl6/J mice over 7 − 21 days (D) using commercial probes (MMPSense™ and AngioSense™). MMP-12 protein concentration and activity were higher in sponges during early angiogenesis (D 3 − 7) when gene expression of vascular endothelial growth factor (a proangiogenic marker) was also high. Gene expression for MMP-12 and platelet-derived growth factor receptor (a marker of vascular maturation) were both higher on D 21 as angiogenesis started to stabilise. The MMP-12 activity probe was unsuccessful in selectively detecting MMP-12 activity in sponge lysate mixtures from D 7 − 21. Administration of an MMP-12 inhibitor did not increase angiogenesis in the sponges in vivo. Additionally, sponges implanted in MMP-12-/- mice did not exhibit significant changes in angiogenesis or MMP activity when imaged in vivo using commercial probes (MMPSense™ and AngioSense™) on D 7. Supporting this, histological analysis of the sponges (removed on D 21) showed that deletion of MMP-12 also did not increase angiogenesis within the sponges.

Compelling evidence indicated that major risk factors for atherosclerosis such as oxidatively modified low density lipoprotein (oxLDL), high glucose, and reactive oxygen species promote endothelial cell apoptosis and thereby may contribute to the initiation of atherosclerotic lesion formation. Using fast protein liquid chromatography (FPLC), plasma LDL from familial hypercholesterolemic (FH) patients were separated into five subfractions, L1¡VL5. Among them, L5 subfraction was highly electronegative and suppressed DNA synthesis in cultured bovine aortic endothelial cells (BAEC) and stimulated mononuclear cell adhesion to cultured endothelial cells in vitro. Because impaired angiogenesis plays an important role in the pathogenesis of atherosclerosis, the anti-angiogenic functions of LDL subfractions from FH subjects were examined. Subconfluent BAEC (6 to 10 passages) maintained in DMEM containing 10% serum were treated with LDL subfractions at a dose of 20 £gg/ml, and the effects on anti-angiogenic functions, including cell proliferation, migration, apoptosis, tube formation, and secretion of matrix metalloproteinase (MMP) were determined. Similar to Cu2+ ox-LDL, FH-L4 and FH-L5 inhibited cell proliferation to 80.9¡Ó2.4% (p<0.05) and 58.5¡Ó4.3% of control (p<0.001), respectively, while the other FH (L1-L3) and all subfractions isolated from normocholesterolemic (N) subjects had negligible effects. Similarly, FH-L4 and -L5, but not FH-L1 to -L3, retarded cell migration to 326.9 ¡Ó 19.4 (p<0.05) and 215¡Ó16 cells (p<0.001 with the control values of 402¡Ó34 cells), respectively. FH-L5 induced almost 20% of BAEC to undergo apoptosis; FH-L4 caused very mild effects, and other subfractions did not affect apoptosis In addition, FH-L4 and -L5 perturbed tube formation by BAEC in culture (5.8¡Ó0.2 and 3.4¡Ó0.4, respectively, versus control 8.5¡Ó1.5 tubes). Finally, FH-L4 and -L5 inhibited secretion of MMP-2 by BAEC (72.7¡Ó6.9 and 18.9¡Ó4.8% of control, respectively). The results demonstrate that FH-L5 potently affects multiple processes that are vital to normal angiogenesis, FH-L4 had milder effects, and other FH and N subfractions had negligible effects. In turn, these effects in vitro on processes pivotal to angiogenesis are consistent with potential effects of ox-LDL on endothelial dysfunction during atherogenesis in vivo.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

Η κιρσοκήλη αποτελεί τη συχνότερη αιτία ανδρικής υπογονιμότητας και ορίζεται ως η παθολογική κιρσοειδής διεύρυνση των φλεβών του σπερματικού τόνου (ελικοειδούς πλέγματος). Η επίπτωση της κιρσοκήλης στο γενικό πληθυσμό κυμαίνεται σε ποσοστό 15‐20%, ενώ στους υπογόνιμους άνδρες αγγίζει το 40%. Παρά το γεγονός ότι η κιρσοκήλη είναι σπάνια στα παιδία, πρόσφατες μελέτες έδειξαν πως το ποσοστό της αγγίζει το 6% σε παιδιά ηλικίας 10 ετών, ενώ στους εφήβους το αντίστοιχο ποσοστό ανέρχεται στο 16%. Πιθανότατα, προκαλείται λόγω ανεπάρκειας των φλεβικών βαλβίδων, κάτι που σαν αποτέλεσμα έχει την παλινδρόμηση του αίματος εντός των σπερματικών φλεβών. Η κιρσοκήλη εμφανίζεται κυρίως στην αριστερή πλευρά, εξαιτίας της ανατομίας των φλεβών στην περιοχή αυτή. Παρά την αυξημένη συχνότητα της, η παθοφυσιολογία της παραμένει εν πολλοίς άγνωστη. Πρόσφατες μελέτες σε κιρσοειδείς φλέβες κάτω άκρων έχουν δείξει ότι η μείωση του ρυθμού απόπτωσης σχετίζεται με την εμφάνιση πρωτοπαθούς φλεβίτιδας. Επιπλέον αυξημένη παραγωγή των συστατικών της εξωκυττάριας θεμέλιας ουσίας, οδηγεί στις μορφολογικές αλλοίωσεις και στην απώλεια του φλεβικού τόνου που χαρακτηρίζει τους κιρσούς κάτω άκρων. Σκοπός: Θεωρώντας ότι αντίστοιχοι μηχανισμοί πρέπει να ισχύουν όχι μόνο στους κιρσούς κάτω άκρων αλλά και στην κιρσοκήλη, υποθέσαμε ότι στο τοίχωμα των κιρσοειδών έσω σπερματικών φλεβών θα παρατηρείται κατ’ αναλογία μείωση του ρυθμού απόπτωσης και αύξηση στο ρυθμό σύνθεσης των συστατικών της εξωκυττάριας θεμέλιας ουσίας με μείωση της έκφρασης των MMPs (MMP‐1, MMP‐ 9) και αντίστοιχη αύξηση των TIMPs (TIMP‐1). Μέθοδοι: Το υλικό μελέτης αποτελούσαν 45 δείγματα έσω σπερματικών φλεβών ασθενών με κιρσοκήλη. Σαν μάρτυρες χρησιμοποιήθηκαν κλάδοι των κάτω επιγαστρικών φλεβών που αφαιρέθηκαν από τον κάθε ασθενή κατά τη διάρκεια χειρουργικής επέμβασης, έτσι ώστε ο κάθε ασθενής να αποτελεί και τον δικό του μάρτυρα. Προσδιορίσαμε τις μορφολογικές αλλοιώσεις στο αγγειακό τοίχωμα με ανοσοϊστοχημική χρώση έναντι της ακτίνης. Επιπλέον, μελετήσαμε την έκφραση των MMP‐1 και MMP‐9 καθώς και του TIMP‐1 στο τοίχωμα των κιρσοειδών όσο και των υγιών φλεβών. Τέλος, το σύνολο των δειγμάτων, εξετάσθηκαν ανοσοϊστοχημικά για την ανίχνευση των μεσολαβητών που ρυθμίζουν το ενδογενές (Bcl‐2, Cas‐9) και το εξωγενές (Cas‐8) μονοπάτι της απόπτωσης. Αποτελέσματα: Συγκριτικά με τις φυσιολογικές φλέβες, οι κιρσοειδείς εμφάνισαν πάχυνση του μέσου χιτώνα. Οι MMP‐1 και TIMP‐1 εκφράσθηκαν στο κυτταρόπλασμα των λείων μυϊκών κυττάρων του μέσου χιτώνα των αγγείων, τόσο στις φυσιολογικές όσο και στις κιρσοειδώς διευρυμένες, με την ένταση της έκφρασης όμως, να είναι μεγαλύτερη στους κιρσούς. Η MMP‐9 εντοπίσθηκε στο κυτταρόπλασμα των λείων μυϊκών κυττάρων του μέσου χιτώνα μόνο των κιρσών. Όσον αφορά την έκφραση των αποπτωτικών δεικτών, παρατηρήσαμε έκφραση της Cas‐9 στο πυρήνα των λείων μυϊκών κυττάρων του μέσου χιτώνα τόσο στις κιρσοειδείς φλέβες όσο και στους μάρτυρες, με την ένταση να είναι μεγαλύτερη στους κιρσούς. Σε μικρό αριθμό δειγμάτων παρατηρήσαμε πυρηνική χρώση της Cas‐ 8 στα λεία μυϊκά κύτταρα του μέσου χιτώνα στους κιρσούς. Bcl‐2 δεν ανιχνεύθηκε σε κανένα από τα δείγματα που εξετάσθηκαν.Συμπεράσματα: Τα δεδομένα μας έδειξαν υπερτροφία των λείων μυϊκών κυττάρων του μέσου χιτώνα των αγγείων στις κιρσοειδείς φλέβες. Επιπλέον παρατηρήσαμε αυξημένη έκφραση των δεικτών Cas‐9, MMP‐1, MMP‐9 και TIMP‐1 στις κιρσοκήλες σε σύγκριση με τους μάρτυρες. Η έκφραση των δεικτών αυτών ήταν ανεξάρτητη από παραμέτρους όπως ο βαθμός (Grade) της κιρσοκήλης και η ηλικία των ασθενών. Τα ευρήματα μας αυτά δεν συνάδουν με αντίστοιχα από κιρσούς κάτω άκρων υποδηλώνοντας ότι πιθανώς άλλοι μηχανισμοί εμπλέκονται στην πρόκληση των κιρσοειδώς διευρυμένων έσω σπερματικών φλεβών. / Background: Varicocele is the most common cause of male infertility, defined as the abnormal varicose enlargement of the scrotal portion of the spermatic veins (pampiniform plexus). The incidence of varicocele in the general population ranges from 15% to 20%, while in subfertile men it reaches 40%. In children the frequency of varicocele is considered to be rare but recent studies have shown its presence in 6% of children aged 10 years, while in adolescents this figure rises up to 16%. Probably caused by insufficient venous valves which cause retrograde flow into the spermatic veins. Varicocele occurs predominately on the left side because of the anatomy of the veins in this region. Despite its great frequency, its pathophysiology remains unclear. Recent studies from varicose veins in the legs have shown that the reduction of rate of apoptosis is associated with the occurrence of primary varicose veins. Furthermore an increased production of the components of the extracellular matrix, leads to morphological alterations and loss of venous tone that characterizes varicose veins in the legs. Purpose: Considering that similar mechanisms should apply not only to lower limbs varicose veins but also at vericocele, we hypothesized that the medial wall of internal spermatic veins should show correspondenly a reduction in the rate of apoptosis and an increase in the rate of synthesis of components of the extracellular matrix by reducing expression of MMPs (MMP‐1, MMP‐9) and a corresponding increase in TIMPs (TIMP‐1). Methods: The study group consisted of 45 samples of internal spermatic vein (ISV) from patients with varicocele. Normal subcutaneous veins were harvested from each patient at the time of surgery and used as control specimens, so that each patient would serve as its own control. Both pathological ISVs and normal subcutaneous veins were used to detect the mediators that regulate the instrinsic (Bcl‐2 and Caspase‐9) and extrinsic (Caspase‐8) apoptotic pathways by immunohistochemical staining. We also investigated matrix metalloproteinases (MMPs) and also their inhibitors (TIMPs) expression in the varicose ΙSV, including MMP‐1, MMP‐9 and TIMP‐1. Finally, we examined the morphological alterations of varicose veins by immunohistochemical staining of Anti‐Actin antibody. Results: Compared with normal veins, a thickening of the smooth muscle layer of the ISV, was found in patients with varicocele. MMP‐1 and TIMP‐1 were expressed within cytoplasm of smooth muscle cells in media of both normal and varicose veins, but normal veins expressed less ΜΜP‐1 and TIMP‐1 than varicoceles did. MMP‐9 was localized to cytoplasm of smooth muscle cells only in varicose veins. As for the expression of apoptotic proteins, we showed expression of Cas‐9 within nuclei of smooth muscle cells in media of both normal and varicose veins however the expression was higher in varicoceles. In small number of samples we noticed nuclear staining of Cas‐8 within nuclei of smooth muscle cells in varicoceles. Bcl‐2 was not detected with immunohistochemistry in any specimens examined. Conclusions: Our data showed vascular smooth muscle hypertrophy in the diseased vessels. We also noticed increased expression of Cas‐9, MMP‐1, MMP‐9 and TIMP‐1 in varicoceles compared with normal veins. The expression of these markers was independent on factors such as the degree of varicocele and the age of the patients. Our findings are not consistent with corresponding varicose veins from legs, suggesting that other mechanisms are probably involved in causing vericoceles.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Lic.-avh. (sammanfattning) Umeå : University. / Härtill 3 uppsatser.