Matrix Metalloproteinases in Asthma-Associated Airway Remodeling – Dr. Jekyll or Mr. Hyde ?

Matrix metalloproteinases (MMPs) are Zn2+-dependent endoproteases, which digest extracellular matrix (ECM) components and various non-ECM molecules. Main physiological role of MMPs concerns regulation of tissue remodeling and regeneration. The production and activity of MMPs are tightly supervised by multistage control mechanisms. These mechanisms include regulation of gene expression, and various post-transcriptional/post-translational modifications. However, without proper control MMPs reveal dual nature, similarly to character from the novella by R.L. Stevenson, “Strange Case of Dr Jekyll and Mr Hyde”. They become dangerous molecules, involved in cancer metastasis, or cardiovascular diseases

The MMP-9/TIMP-1 imbalance and the reduced level of TGF-β in the cervical area of amniotic membrane is a possible risk factor of PROM and premature labor — proof-of-concept study

Objectives: To assess the level MMP-9, TIMP-1 and TGF-β in placental and cervical region of amniotic membranes derived from at-term, pre-term and PROM deliveries. Material and methods: 14 amniotic membranes have been assessed; the quantitative analysis of MMP-9, TGF-β and TIMP-1 was assayed using respective Quantikine Immunoassay Kit. Results: The MMP-9 level in PROM samples was similar to the level of MMP-9 in at-term membranes and comparable between the cervical and placental region of these membranes. The concentration of TGF-β and TIMP-1 was decreased in the cervical area of AM derived from deliveries complicated with PROM. Conclusion: The MMP9/TIMP-1 imbalance, as well as the reduced level of TGF-β may be possible risk factors of pre-term labor and PROM

Recurrent carotid artery stenoses

Jednym z poważniejszych powikłań po udrożnieniach tętnic szyjnych są ich nawrotowe zwężenia. Ze względu na przebieg kliniczny oraz obraz histologiczny miejsca po operowanej tętnicy szyjnej wyróżnia się zwężenia nawrotowe wczesne i późne. Mianem restenozy wczesnej określa się zwężenie, które powstaje w ciągu pierwszych 2 lat po zabiegu operacyjnym. Podłożem nawrotu zwężenia w tym okresie jest intymalna hiperplazja. Zwężenie to charakteryzuje się niskim ryzykiem powikłań neurologicznych. Zwężenia późne są to zmiany powstające w późniejszym okresie po zabiegu. W badaniach patomorfologicznych nie różnią się one od zmian pierwotnych. Również ryzyko powikłań neurologicznych jest podobne jak w przypadku zwężeń pierwotnych. Konieczność reoperacji zachodzi w razie zwężeń zagrażających okluzją tętnicy szyjnej wewnętrznej lub w zmianach powodujących objawy neurologiczne. Wyniki odległe powtórnych zabiegów operacyjnych są podobne do operacji pierwotnych, jednak istnieje większe ryzyko powikłań śród- i pooperacyjnych. Nadal jednoznacznie nie określono roli zabiegów śródnaczyniowych w leczeniu zwężeń pierwotnych i wtórnych.Recurrent stenoses belong to the gravest complications after interventions of patency restoration of carotid arteries. According to the clinical course and the histological picture of the arterial site after intervention, recurrent stenoses are classified as either early or late. The term of early restenosis refers to arterial narrowing which occurs within the first two years following the procedure. In this period, recurrence of stenosis is caused by intimal hyperplasia. This type of stenosis bears a low risk of neurological complications. Late stenoses occur in the later period after the initial procedure. They do not differ from the primary lesions on pathomorphological grounds, and their risk of causing neurological complications is similar to that of the primary arterial narrowings. Stenoses bearing high risk of complete occlusion of carotid artery or provoking neurological symptoms necessitate reoperation. Although long-term results of repeated operations are similar to those of primary interventions, higher risk of intra- and postoperative complications should be taken into account. The role of endovascular interventions in primary and secondary arterial stenoses remains not unequivocally determined

Hemosyderyna wydalana w moczu jako marker przewlekłych zaburzeń żylnych

Wstęp. Ze względu na dużą powszechność występowania przewlekłe zaburzenia żylne stanowią poważny problem społeczny krajów rozwiniętych. Istotną rolę w patomechanizmie rozwoju zmian troficznych skóry w przebiegu niewydolności żylnej odgrywają tkankowe depozyty związków żelaza. Celem badania była ocena wydalania hemosyderyny w moczu u osób z objawami przewlekłych zaburzeń żylnych. Materiał i metody. Badano osad pochodzący z moczu, w którym wybarwiano kryształy hemosyderyny za pomocą roztworu Perla. Przebadano 76 osób, u których niewydolność żylna była w różnych stopniach zaawansowania klinicznego. Wyniki. Nie wykazano istnienia związku pomiędzy liczbą wydalanych w moczu kryształów a stopniem nasilenia patologii układu żylnego. Wnioski. Hemosyderyny nie można traktować jako wyznacznika nasilenia patologii żylnej.Background. Chronic venous insufficiency (CVI) is one of the most significant health problems of developed countries. Tissue deposits of iron play an important role in the pathogenesis of trophic skin changes. The purpose of the study was to test the correlation of clinical severity of venous insufficiency with urine excretion of hemosiderin. Material and methods. Urine sediments were stained for hemosiderin granules with Perl reagent. The urine samples of 76 persons representing various categories of venous insufficiency were evaluated. Results. There was no correlation between clinical category of venous insufficiency and number of hemosiderin granules noticed in urine. Conclusions. Thus, hemosiderinuria cannot be a marker of severity of venous disturbances

Buflomedil associated with pentoxifylline in the treatment of patients with intermittent claudication. Opened, randomised, one-centre-based study

Wstęp. Modyfikacja stylu życia i ograniczenie czynników ryzyka rozwoju miażdżycy poprawiają dystans marszu u chorych z chromaniem przestankowym. W leczeniu tych dolegliwości stosuje się jednocześnie wiele preparatów farmakologicznych. Postanowiono zbadać, czy skojarzone leczenie farmakologiczne będzie wpływało na zwiększenie dystansu marszu u chorych z chromaniem przestankowym. Materiał i metody. W prospektywnym, randomizowanym badaniu uczestniczyło 79 chorych chorych z przewlekłym niedokrwieniem kończyn dolnych (II stopień według klasyfikacji Fontaine). Chorych leczono przez 12 tygodni skojarzoną terapią buflomedilem (600 mg/d) i pentoksyfiliną (1200 mg/d), albo monoterapią za pomocą wyłącznie pentoksyfiliny (1200 mg/d). U wszystkich pacjentów na początku i na końcu badania przeprowadzono próbę na bieżni ruchomej (tempo marszu 3,2 km/h, nachylenie 12°), mierząc dystans marszu wolny od bólu i całkowity dystans marszu. Wyniki. Dystans marszu wolny od bólu wydłużył się istotnie statystycznie w obu grupach badanych (74,4% - w grupie terapii skojarzonej oraz 27,3% w grupie leczonej pentoksyfiliną). Natomiast całkowity dystans marszu istotnie statystycznie wydłużył się tylko w grupie terapii skojarzonej (41,8%). Odsetek działań niepożądanych był podobny w obu grupach badanych. Wniosek. Skojarzone stosowanie pentoksyfiliny i buflomedilu wydaje się efektywnym i bezpiecznym leczeniem u chorych z chromaniem przestankowym u chorych.Background. It has been known that modification of risk factors for atherosclerosis improves the walking distance of patients with intermittent claudication. On the other hand there are variety of different drugs widely used by physicians to meet the patients expectations. We decided to study whether a combine medical therapy has an impact on walking distance among the patients with intermittant claudication. Material and methods. In a randomised, prospective study, 79 patients with chronic arterial occlusive disease (Fontaine stage II) were treated either by buflomedil (600 mg daily) and pentoxifylline (1200 mg daily) or by pentoksyfilline (1200 mg daily) alone over 12 weeks. All patients underwent treadmill testing at the beginning and at the end of the study (treadmill speed 3,2 km/h and of 12° incline). The pain-free and maximal walking distance were measured at both time points. Results. The pain-free distance was significantly improved in both groups (74,4% - buflomedil and pentoxifylline group and 27,3% - pentoxifylline group) whereas the total walking distances was significantly higher only in the group of treated by buflomedil and pentoxifylline (41,8%). The percentage of side-effects and adverse events were equal among the studied groups. Conclusion. The combine treatment of buflomedil with pentoxifylline turned out to be effective and safe for the patients with intermittent claudication

Vergleichende STM-basierte Studie der thermischen Evolution von Co- und Ni-Germanid-Nanostrukturen auf Ge(001)

Since 1947, when Bardeen and Brattain initiated the era of microelectronics by constructing the first Germanium (Ge) transistor, semiconductors have become the main material platform for advanced integrated circuit (IC) technologies. Later on, given in particular the electrical stability of its native oxide, IC technology shifted from Ge to Silicon (Si) substrates and the dominance of Si-based complementary metal oxide semiconductor (CMOS) microelectronics is today unquestionable. However, as the semiconductor industry is approaching the limits of traditional Si CMOS scaling, the integration of new materials into Si micro- and nano-electronics is required to extend the performance and functionality of future CMOS-based IC technologies. Recently, Ge due to its superior optoelectronic properties and compatibility with conventional Si CMOS technology has re-emerged as an alternative semiconductor material on the mainstream Si technology platform. Many of the Ge integration challenges, such as e.g. doping, epitaxial quality etc., have been recently solved or minimized to an acceptable level. However, the fabrication of low resistance, thermally stable metal/Ge contacts is still one of the main barriers towards the full use of the potential offered by Ge. In particular, the formation of ohmic contacts is relevant for applications where high current densities are of importance (i.p. Ge p-MOSFET and Ge laser applications). Consequently, intensive investigations of metal/Ge contacts are imperative for future applications of Ge. Various metal/Ge contact systems were studied and demonstrated good thermal stability and promising electrical properties. However, given their widespread use in Si CMOS technologies in form of their respective silicides, Co- and Ni-germanides seem to be an obvious choice for electrical contacts in Ge-based devices. Both metal/Ge systems exhibit a complex bulk phase diagrams with a wide range of different physical properties. It is generally acknowledged that the stoichiometric CoGe2 and NiGe phases are best suited for ohmic metal contact formation, mainly due to their low resistivity. It is worth noting that the bulk phase diagram is limited in its use for nanoscience due to an increased surface/volume ratio as well as by the strong nanostructure/substrate interface influence. This PhD thesis sheds light on the formation process at the atomic level of Co and Ni germanide nanostructures on clean, reconstructed Ge(001) substrates. The main part of the presented research is based on in-situ scanning tunneling microscopy (STM) studies on the influence of subsequent, post-evaporation annealings at various temperatures in order to follow and investigate on the nano-scale the structural evolution of a few monolayers of Co and Ni metal (deposited at RT and in UHV conditions) on an atomically clean, reconstructed Ge(001) surface. Furthermore, additional techniques like LEED, (S)TEM-EDX and XPS were used to corroborate and complement the STM derived insights. It was demonstrated that - for both investigated systems - room temperature deposition of a few metal monolayers on clean Ge(001) results in a Volmer Weber growth mode. Starting with annealing treatments at relatively low temperature ranges, the formation of a continuous MetalxGey wetting layer from as-deposited 3D metal clusters on Ge(001) was detected. It should be noted that a very flat wetting layer was observed for the Co/Ge(001) system, which is different for the Ni/Ge(001) system where inhomogeneous terraced domains were formed. Finally, the 2D wetting layer gradually evolves with increasing temperature into well-ordered 3D MetalxGey nanostructures, surrounded by clean, reconstructed Ge(001). Analysis of these Co and Ni germanide nanostructures shows that the growth mechanism is different: in particular the Ni/Ge system is more reactive by means of Ni bulk diffusion and results in 3D Ni germanide nanostructures which show a strong tendency to be embedded into the Ge(001) substrate. In contrast, Co germanide nanostructures are situated initially on top of the Ge(001) substrate due to the fact that Ge diffusion dominates in the low temperature range. Only at higher annealing temperatures, Co diffusion into the bulk occurs and Co germanide nanostructures penetrate into the Ge substrate. For the Co- as well as Ni-Germanide system, the nanostructures undergo Ostwald ripening phenomena in the high temperature range. The present PhD thesis thus allows to understand on the nano-scale the main growth and reaction mechanisms of the Walser and Benè rule set up about 40 years ago to describe metal/semiconductor interface reaction on the macro-scale.Seit 1947 als Bardeen und Brattain die Ära der Mikroelektronik, durch die Konstruktion des ersten Germanium (Ge) Transistors, einleiteten, wurden Halbleiter zur Hauptgrundlage für fortschrittliche „integrated circuit“ (IC)-Technologien. Später wechselten IC-Technologien von Ge zu Silizium (Si)-Substraten, bedingt durch die elektrische Stabilität der natürlichen Oxide, wodurch die Dominanz von Si-basierten „complementary metal oxide semiconductor“ (CMOS) Mikroelektronik unangefochten wurde. Jedoch wird, durch die Annäherung an die Limitierung der traditionellen Si-CMOS-Skalierung, die Integration von neuen Materialien in die Si-Mikro- und Nanoelektronik notwendig, um die Leistung und Funktionalität von zukünftigen CMOS-basierten IC-Technologien weiter auszubauen. Jüngst hat sich Ge, durch seine optoelektronische Eigenschaften und Kompatibilität mit konventionellen Si-CMOS-Technologien, wieder als alternatives Halbleitermaterial auf einer Si-Technologieplattform hervorgetan. Viele der Ge-Integrationsherausforderungen, wie z.B. Dotierung, epitaktische Qualität etc., wurden mittlerweile gelöst oder auf ein akzeptables Niveau reduziert. Jedoch ist die Herstellung von niederohmigen, thermisch stabilen Metall/Ge-Kontakten immer noch eine der Hauptbarrieren zur vollständigen Nutzung des Potentials von Ge. Die Bildung von ohmschen Kontakten ist insbesondere für Anwendungen mit hohen Stromdichten (z.B. p-MOSFET und Laser) von großer Relevanz. Entsprechend sind intensive Untersuchungen von Metall/Ge-Kontakten zwingend notwendig für zukünftige Anwendungen von Ge. Es wurden diverse Metall/Ge-Systeme studiert, welche eine gute thermische Stabilität und vielversprechende elektrische Eigenschaften demonstrierten. Co- und Ni-Germanide, in Betracht ihrer weiten Verbreitung in CMOS-Technologien als entsprechende Silizide, scheinen offensichtlich eine gute Wahl für elektrische Kontakte in Ge-basierten Bauteilen zu sein. Beide Metall/Ge-Systeme weisen ein komplexes Volumenphasendiagramm, mit unterschiedlichsten physikalischen Eigenschaften, auf. Es ist allgemein anerkannt, dass die CoGe2- und NiGe-Phase sich am besten als ohmsche Metallkontakte durch ihren geringen Widerstand eignen. Es sollte erwähnt werden, dass das Volumenphasendiagramm in der Anwendbarkeit in den Nanowissenschaften, durch die erhöhte Oberflächen/Volumen-Ratio genauso wie durch den starken Nanostruktur/Substrat-Einfluss, limitiert ist. Diese Dissertation soll die Bildungsprozesse von Co- und Ni-Germanidnanostrukturen auf sauberen, rekonstruierten Ge(001) Substraten auf einem atomistischen Niveau näher beleuchten. Der Hauptteil der hier präsentierten Forschung basiert auf in-situ „scanning tunneling microscopy“ (STM)-Studien, bezüglich des Einflusses von aufeinanderfolgenden Temperschritten bei unterschiedlichen Temperaturen, um die nanoskalierte, strukturelle Evolution von wenigen Monolagen Co- und Ni-Metall nach der Abscheidung (bei RT und unter UHV-Bedingungen) auf einer atomar reinen, rekonstruierten Ge(001)-Oberfläche zu verfolgen und zu untersuchen. Des Weiteren wurden zusätzliche Techniken wie LEED, (S)TEM-EDX, und XPS verwendet, um die mit STM erzielten Ergebnisse zu bekräftigen und zu vervollständigen. Es wurde demonstriert, dass für die beiden untersuchten Systeme die Raumtemperatur-abscheidung von wenigen Monolagen Metall auf reinem Ge(001) in einem Volmer-Weber-Wachstumsmodus resultiert. Temperschritte bei relativ niedrigen Temperaturen führten anfangs zur Detektion von kontinuierlichen MetallxGey Benetzungsschichten ausgehend von den abgeschiedenen 3D Metallclustern auf Ge(001). Zu beachten ist, dass eine sehr flache Benetzungsschicht für das Co/Ge(001) beobachtet wurde, was sich zu dem Ni/Ge(001)-System unterscheidet, wo sich inhomogene Domänen mit Terrassen bildeten. Mit ansteigender Temperatur entwickelt sich die 2D Benetzungsschicht allmählich zu wohlgeordneten 3D MetallxGey Nanostrukturen umgeben von sauberen, rekonstruierten Ge(001)-Flächen. Eine genaue Analyse dieser Co- und Ni-Germanid-Nanostrukturen zeigt, dass ihre Wachstumsmechanismen unterschiedlich sind. So ist das Ni/Ge-System reaktiver, was sich durch eine erhöhte Ni-Volumendiffusion andeutet, wodurch sich eine starke Tendenz zu in Ge(001) eingebetteten 3D Ni-Germanid-Nanostrukturen ergibt. Im Gegensatz dazu befinden sich Co-Germanid-Nanostrukturen anfänglich auf dem Ge(001)-Substrat, da die Germaniumdiffusion bei niedrigen Temperaturen dominiert. Nur bei höheren Temperaturen tritt eine Co-Diffusion auf und die Co-Nanostrukturen dringen in das Ge-Substrat ein. Sowohl für das Co- sowie auch das Ni-Germanid-System vollziehen die Nanostrukturen einen Ostwald-Reifungsprozess bei hohen Temperaturen. Die vorliegende Dissertation erlaubt so Einblicke in das Verständnis von nanoskalierten Wachstums- und Reaktionsmechanismen der Walser und Benè Regeln, die schon vor 40 Jahren aufgesetzt wurden, um die Metall/Halbleiter-Grenzflächenreaktion auf einer makroskopischen Skala zu beschreiben

Hemodynamic and Radiological Classification of Ovarian Veins System Insufficiency

Ovarian veins system insufficiency is one of the most common reasons for pelvic venous insufficiency (PVI). PVI is a hemodynamic phenomenon responsible for the occurrence of venous insufficiency of the lower extremities and recurrent varicose veins in nulliparous and parous women, as well as for a set of symptoms described as pelvic congestion syndrome (PCS). In the years 2017–2019, 535 patients admitted to our center with symptoms of venous insufficiency of the lower extremities, underwent complete ultrasound diagnostics (color-duplex ultrasound) of the venous system of the abdomen, pelvis and lower limbs, as well as extended imaging diagnostics using computed tomography (CT) or magnetic resonance (MR) venography. On the basis of the obtained results, the authors proposed a 4-grade hemodynamic and radiological classification (grades I-IV) defining the stratification of ovarian veins insufficiency. Using the above mentioned classification approx. 32% patients were identified as Grade I and I/II, approximately 35% revealed morphological and hemodynamic changes corresponding to Grade II and II/III, approximately 25% were classified as Grade III, whereas the remaining 8% were assessed as Grade IV. The described classification allows for the grading of ovarian veins insufficiency based on transparent radiological criteria, making it easy to use in everyday clinical practice. According to the authors, the proposed classification could facilitate communication between diagnostic physicians, specialists dealing with the treatment of venous insufficiency and gynecologists, who admit patients with symptoms suggesting venous insufficiency of the pelvis

Two-Year Follow-Up after Endovenous Closure with Short-Chain Cyanoacrylate versus Laser Ablation in Venous Insufficiency

Background: The current treatment of venous disease is focused on the minimally invasive exclusion of the affected vein. Besides widely used thermal ablation, chemical ablation with cyanoacrylate, reported as safe and highly effective, has been gaining increasing interest. Patients and methods: In the current report, we present data from a two-year observation in 89 patients (61 female/28 male, mean age 44.3 ± 13.5) suffering from venous insufficiency (C2–C4), treated either using short-chain cyanoacrylate, the VenaBlock system (n = 43) or laser thermoablation with ELVeS 1470 (n = 46). The assessment comprised the occurrence of venous disease-related symptoms and the ultrasound examination of the leg venous system. Results: The frequency of recanalization after 2 years from the VenaBlock procedure was significantly higher than after laser treatment (37.2 vs. 8.7%). Apart from recanalization, in some individuals from both groups, the symptoms of recurrence and/or disease progression, including the development of insufficiency in other veins of treated or contralateral legs (9.3 vs. 15.2% and 9.3 vs. 17.4%, respectively), were observed. Unexpectedly, the general prevalence of the disease progression did not differ significantly between the VenaBlock and ELVeS groups (44.2 vs. 34.8%, respectively). Conclusions: Despite the higher recanalization rate of VenaBlock compared to ELVeS, the overall effectiveness of cyanoacrylate and laser thermoablation after two years was similar. Therefore, both methods similarly failed to prevent recurrence and disease progression, which seem to be method-independent