Hybrid debranching and TEVAR of the aortic arch off-pump, in re-do patients with complicated chronic type-A aortic dissections : a critical report

Background: Patients suffering from acute type A aortic dissection undergo replacement of the ascending aorta, the proximal hemiarch or complete aortic arch, depending on the extent of the individual pathology. In a subset of these treated patients, secondary pathologies of the distal anastomosis or the remaining distal part of the aorta occur. The treatment of these pathologies is challenging, requiring major surgical re-do procedures with aortic arch replacement under extracorporeal circulation and hypothermic circulatory arrest. Methods: We report our experience of five patients with complex aortic pathologies after previous aortic surgery treated with a single stage re-do hybrid procedure, consisting of bypass grafting of the supraaortic branches off-pump, stent graft placement for endovascular aortic repair (TEVAR) and surgical debranching of the aortic arch. Results: In all patients the surgical vascular grafts and stent grafts were deployed successfully, there were no intraoperative deaths. Four out of five patients were discharged from hospital in good clinical condition. One patient died postoperatively due to cardiac tamponade. In one patient a type I endoleak persisted leading to occlusion of a bypass branch requiring surgical revision at one year after debranching. Conclusion: We discuss the prerequisites, all steps and potential pitfalls of this hybrid aortic arch replacement. The current procedure avoids cardiopulmonary bypass and circulatory arrest, which may benefit early patient outcome; however, patient and device selection plays a key role for immediate success and midterm outcomes. In addition, precise procedural planning and development of customized stents may help to develop this procedure into a true alternative for conventional aortic arch replacement

Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced Porcine Failing Heart Model

For treatment of advanced heart failure, current strategies include cardiac transplantation or blood-contacting pump technology associated with complications, including stroke and bleeding. This study investigated an individualized biventricular epicardial augmentation technology in a drug-induced porcine failing heart model. A total of 11 pigs were used, for the assessment of hemodynamics and cardiac function under various conditions of support pressures and support durations (n = 4), to assess device positioning and function by in vivo computer tomographic imaging (n = 3) and to investigate a minimally invasive implantation on the beating heart (n = 4). Support pressures of 20-80 mmHg gradually augmented cardiac function parameters in this animal model as indicated by increased left ventricular stroke volume, end-systolic pressures, and decreased end-diastolic pressures. Strong evidence was found regarding the necessity of mechanical synchronization of support end with the isovolumetric relaxation phase of the heart. In addition, the customized, self-expandable implant enabled a marker-guided minimally invasive implantation through a 4cm skin incision using fluoroscopy. Correct positioning was confirmed in computer tomographic images. Continued long-term survival investigations will deliver preclinical evidence for further development of this concept

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

Two experiments were conducted to determine: 1) whether the adult male transgenic sickle cell mouse (Tg58 × Tg98; TSCM), exhibits the patterns of reproductive endpoints (hypogonadism) characteristic of men with sickle cell disease (SCD) and 2) whether hydroxyurea (HU) exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM) (N = 10/group) for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline) as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ± 0.004g) that was further decreased on day 56 (0.06 ± 0.003g; treatment x time interaction) compared with controls (day 28, 0.15 ± 0.01g; day 56, 2, 0.16 ± 0.01g). Concomitant with a 52% shrinkage (P<0.001) in area of testes in 56 days of HU treatment, testes from HU-treated TSCM exhibited significant atrophic degeneration in the seminiferous tubules compared with controls. Furthermore, treated TSCM had only Sertoli cells and cell debris remaining in most of the seminiferous tubules in comparison with controls. Leydig cell prominence and hyperplasia were more evident (P<0.05) in the steroidogenic compartments of testes of HU-treated TSCM compared with controls. However, plasma testosterone concentrations were reduced by HU treatment (P<0.05; treatment x time interaction) compared with controls on the two time periods studied. Epididymides from HU-treated TSCM sustained a 25% shrinkage (P<0.05), along with 69 (P<0.005) and 95% reduction (P<0.005), in stored sperm density and sperm progressive motility (treatment x time interaction P<0.05), respectively on day 56 of treatment compared with controls. These data demonstrate that TSCM used in this study exhibited SCD-induced hypogonadism, thus authenticating their use for studying the effect of HU on male reproductive endpoints observed in SCD patients. Secondarily, our data show that HU treatment exacerbated the already SCD-induced hypogonadism to gonadal failure

Increased Inducible Nitric Oxide Synthase Expression in Organs Is Associated with a Higher Severity of H5N1 Influenza Virus Infection

BACKGROUND: The mechanisms of disease severity caused by H5N1 influenza virus infection remain somewhat unclear. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. However, enzymes of the nitric oxide synthase (NOS) family such as the inducible form of NOS (iNOS) generate NO, which serves as a potent anti-viral molecule to combat infection in combination with acute phase proteins and cytokines. Nevertheless, excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: There are dramatic differences in the severity of disease between chickens and ducks following H5N1 influenza infection. Chickens show a high level of mortality and associated pathology, whilst ducks show relatively minor symptoms. It is not clear how this varying pathogenicty comes about, although it has been suggested that an overactive inflammatory immune response to infection in the chicken, compared to the duck response, may be to blame for the disparity in observed pathology. In this study, we identify and investigate iNOS gene expression in ducks and chickens during H5N1 influenza infection. Infected chickens show a marked increase in iNOS expression in a wide range of organs. Contrastingly, infected duck tissues have lower levels of tissue related iNOS expression. CONCLUSIONS/SIGNIFICANCE: The differences in iNOS expression levels observed between chickens and ducks during H5N1 avian influenza infection may be important in the inflammatory response that contributes to the pathology. Understanding the regulation of iNOS expression and its role during H5N1 influenza infection may provide insights for the development of new therapeutic strategies in the treatment of avian influenza infection

Lehrstückunterricht gestalten. Linnés Wiesenblumen, Aesops Fabeln, Faradays Kerze. Exemplarische Studien zur lehrkunstidaktischen Kompositionslehre.

In der vorliegenden Dissertation wird zunächst das pädagogische Konzept der Lehrkunstdidaktik in seiner Entwicklung zwischen 1995 (dem Publikationsjahr des Buches „Lehrkunst. Lehrbuch der Didaktik“ von Hans Christoph Berg und Theodor Schulze) und 2003 (dem gemeinsamen Referat von Wolfgang Klafki und Hans Christoph Berg auf dem Kongress „Unterrichtsentwicklung“ in Luzern/CH) dargestellt. Auf dieser Basis wird erörtert, welche Merkmale den Lehrstückunterricht (das ist die charakteristische Unterrichtsform der Lehrkunstdidaktik) konstituierend kennzeichnen. Acht „Lehrstückkomponenten“ kristallisieren sich heraus, welche die Unterrichtsprinzipien des Exemplarischen, Genetischen und Dramaturgischen (nach Martin Wagenschein) konkretisieren. Ausserdem werden Kriterien zur sachgerechten Analyse zusammenfassender Lehrstückdarstellungen in Textform erarbeitet. Dabei wird gezeigt, dass die bildungstheoretischen Überlegungen Wolfgang Klafkis im Konzept der kategorialen Bildung den Bergschen Ansatz der Lehrkunstdidaktik fundieren. Im Hauptteil der Arbeit werden die theoretischen Einsichten im Lehrstückunterricht auf der Sekundarstufe 1 konkretisiert. In ausführlichen Unterrichtsschilderungen, Auswertungen und pädagogisch-didaktischen Reflexionen der Lehrstücke „Linnés Wiesenblumen“, „Aesops Fabeln“ und „Faradays Kerze“ erweisen sich die exponierten Kompositionsmerkmale als praxistauglich hinsichtlich der Analyse, Weiterentwicklung und Neukomposition von Lehrstücken

Studies of the interaction of acetylcholinesterase from Electrophorus electricus with selected inhibitors

Choroba Alzheimera dotyka obecnie coraz większą liczbę osób po 65 roku życia. Jest to nieodwracalna i postępująca degeneracja ośrodkowego układu nerwowego. Podejmowane są próby zaprojektowania nowych leków, które byłyby skuteczne w skutecznym leczeniu tej choroby. Dotychczas wprowadzono do terapii kilka leków o właściwościach hamujących cholinoesterazy (takryna, donepezil, galantamina, rywastygmina). Leki te są inhibitorami i zwiększają poziom acetylocholiny (ACh) w ośrodkowym układzie nerwowym poprzez hamowanie jej rozkładu przez acetylocholinesterazę i butyrylocholinesterazę. Celem pracy było zbadanie oddziaływania acetylocholinesterazy z nowymi związkami hamującymi jej aktywność poprzez wyznaczenie krystalicznych struktur kompleksów białko-ligand. Zakupione preparaty białek oraz zsyntetyzowane inhibitory poddano krystalizacji. Próby otrzymania kryształów kompleksów enzym-inhibitor nie powiodły się. Kryształy nadające się do pomiarów dyfraktometrycznych otrzymano tylko dla inhibitora N24. Rozwiązano i udokładniono jego strukturę. Otrzymana struktura inhibitora N24 może posłużyć jako model w przyszłych badaniach in silico.The number of people under the age of 65 that suffer from Alzheimer disease is constantly growing. Alzheimer disease is irreversible and progressive degeneration of the central nervous system. Numerous attempts are undertaken to design new drugs that are effective in preventing of this disease. Up today several drugs that inhibit cholinesterases have been introduced for the treatment, including tacrine, donepezil, galantamine, rivastigmine. These drugs increase the level of acetylcholine (ACh) in the central nervous system by inhibiting its degradation perfomed by two enzymes: acetylcholinesterase and butyrylcholinesterase. The purpose of presented studies was to investigate the interaction of acetylcholinesterase with the new compounds that inhibit its activity by determining crystal structures of protein-ligand complexes. Crystallization trials for purchased protein samples and synthesized inhibitors were performed. For proteins the crystallization was unsuccessful. The crystals suitable for X-ray data collection were obtained for inhibitor N24. For this compound structure was solved and refined. Determined structure of N24 will serve as a model in future in silico experiments

The Influence of Solvent Addition on Selected Properties of Cores Covered with Protective Coating

Obciążenia cieplne, którym poddawane są formy i rdzenie, powodują termiczne zmęczenie materiału, które może generować tworzenie się wad takich jak: pęknięcia, wżarcia, żyłki, wykruszanie materiału formy podczas zalewania. Może dochodzić także do przypalenia i penetracji metalu do masy formierskiej lub rdzeniowej. Jednym z rozwiązań ograniczającym występowanie niekorzystnych zjawisk jest zastosowanie powłok ochronnych. Nanoszone są one w celu poprawy jakości powierzchni odlewów oraz ułatwienia wyjęcia odlewu z formy. W niniejszym artykule zaprezentowano wstępne wyniki badań wpływu zwiększonej ilości rozcieńczalnika w powłokach, na głębokość penetracji powłoki w głąb rdzeni oraz pomiar parametru hot distortion.Thermal loads applied to moulds and cores cause thermal fatigue and the appearance of flaws such as: cracks, penetration, veins, spalling of mould material during casting. Scorching and penetration of metal into the moulding sand or core sand are also possible. One of the solutions that limit the occurrence of unfavourable phenomena is using protective coatings. They are applied in order to improve the quality of castings and make it easier to extract a casting from the mould. This article presents a general classification of coatings applied to casting moulds and cores. It focusses mainly on protective coatings and describes the methods of applying and drying them. Preliminary results of coating tests are presented, including microscopic observation of the depth of coating penetration into mass and a measurement of the hot distortion parameter relative to the amount of solvent added