Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study.

To evaluate the course of neuropsychological impairment, patients with first-episode schizophrenia and healthy controls were assessed with a comprehensive test battery at the time of index treatment and after a 5- and 15-year follow-up period. Summary scores for verbal intelligence (VBI), spatial organization, verbal fluency, verbal learning, semantic memory, visual memory, delay/retention rate, short-term memory, visual-motor processing and attention (VSM) and abstraction/flexibility were constructed. Our results show that neurocognitive functioning is impaired already at the onset of schizophrenia and remains stable over the 15-year follow-up period with an improvement in VBI. With regard to the presence of a deficit syndrome, it became apparent that the group with a deficit syndrome showed a deterioration of neurocognitive functions during the follow-up period, most pronounced in VSM. On the other hand, the group without a deficit syndrome showed an improvement in neurocognitive functions at the 15-year follow-up, which exceeded the learning effects of healthy control subjects. Neurocognitive performance at index assessment strongly predicted the performance at the 15-year follow-up. Most likely due to the small sample size, there were only weak associations between treatment with different types of neuroleptics and neurocognitive performance.

Amphotericin B concentrations in healthy mallard ducks (Anas platyrhynchos) following a single intratracheal dose of liposomal amphotericin B using an atomizer.

Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3 mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos). Following intratracheal delivery, amphotericin B was present in lung parenchyma at concentrations above the targeted MIC of 1 µg/g for up to 9 days post-administration; however, distribution of the drug was uneven, with the majority of the drug concentrated in one lung lobe. Concentrations in the contralateral lung lobe and the kidneys were above the targeted MIC 1 day after administration but declined exponentially with a half-life of approximately 2 days. Plasma concentrations were never above the targeted MIC. Histological examination of the trachea, bronchi, lungs, heart, liver, and kidneys did not reveal any toxic changes. Using a commercial atomizer, intratracheal delivery of amphotericin B at 3 mg/kg resulted in lung parenchyma concentrations above 1 µg/ml with no discernable systemic effects. Further studies to establish a system of drug delivery to both sides of the pulmonary parenchyma need to be performed, and the efficacy of this treatment for disease prevention remains to be determined.

Antifungal activity, yield, and composition of Ocimum gratissimum essential oil.

Ocimum gratissimum L. or clove basil, belongs to the Lamiaceae family, has various desirable uses and applications. Beyond its aromatic, seasoning, and medicinal applications, this plant also has antimicrobial activity. This study was aimed at assessing the antifungal activity, yield, and composition of the essential oil (EO) of O. gratissimum. The species was cultivated in garden beds with dystrophic red latosol soil type containing high organic-matter content. The EO was obtained by hydrodistillation of dried leaves in a modified Clevenger apparatus, followed by determination of its content. Chemical characterization was carried out by gas chromatography-mass spectrometry (GC-MS). Microbial activity was assessed using the broth microdilution method, by determining the minimum inhibitory concentration (MIC), in order to compare the antimicrobial effect of EO in 10 isolates-Fusarium oxysporum f. sp tracheiphilum (CMM-0033), F. oxysporum f. sp. cubense (CMM-0813 and CMM-2819), F. oxysporum f. sp lycopersici (CMM-1104), F. solani (CMM-3828), Rhizoctonia solani (CMM-3274), and Macrophomina phaseolina (CMM-2715, CMM-3875, CMM-3615, and CMM-3650). The EO was a highly effective inhibitor of the studied phytopathogenic fungi, with MICs varying from 31.25 to 125 µg/mL. F. oxysporum f. sp lycopersici and R. solani were the most sensitive; both were inhibited at an MIC of 31.25 µg/mL. The EO content in the plant extract was 0.18%. Thirty chemical compounds were detected via GC-MS, with linalool (32.9%) being the major compound followed by 1,8-cineole (21.9%), both oxygenated monoterpenes. It can be concluded that clove basil EO is a highly effective antifungal agent, and therefore, a potential alternative for the control of plant pathogenic diseases.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

[Surgical techniques in mitral valve diseases. Reconstruction and/or replacement]. / Operative Techniken bei Mitralklappenerkrankungen. Rekonstruktion und/oder Ersatz.

Mitral valve (MV) disease is one of the most common heart valve diseases. The surgical and interventional treatment for MV disease requires a multidisciplinary approach. For primary mitral valve regurgitation (MVR) surgical MV repair is the treatment of choice, which can be performed with an excellent outcome and long-term survival in reference centers. The surgical technique used for MV repair depends on the pathological mechanism, the morphological dimensions of the MV, the operative risk and the expertise of the cardiac surgeon. The surgical and interventional treatment of secondary MVVR is the subject of on-going discussions. In patients with moderate secondary MVR undergoing coronary artery bypass grafting, concomitant MV repair should be performed. In the presence of severe secondary MR with risk factors for failure of MV repair, patients should consider having MV replacement. In the rare cases of patients presenting with mitral valve stenosis (MVS) MV repair can be considered in young patients and who are most often treated with MV replacement. The choice between biological or mechanical MV replacement depends on the pathophysiology, the comorbidities, the amount of anticoagulation necessary and the age of the patient. New percutaneous techniques for MV replacement offer new treatment options for reoperation in high-risk patients.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

Weight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding.

BACKGROUND: Bladder dysfunction has one of the highest prevalences as a comorbidity of obesity in industrialized countries. The aetiopathogenesis of obesity-associated bladder dysfunction is still obscure, but there is growing evidence that general metabolic changes in obese patients may be in part responsible. As demonstrated recently, high fat diet (HFD) significantly alters the protein expression in the urinary bladder, activates multiple signalling pathways associated with cell survival and inflammation and ultimately provokes bladder fibrosis in an obese rat model. The study aimed to elucidate the role of matrix metalloproteases (MMPs) and their specific tissue inhibitors of metalloproteases (TIMPs) in obesity-related bladder extracellular matrix (ECM) remodelling and the effect of weight loss surgery via sleeve gastrectomy (SG) on phenotype and molecular parameters. METHODS: Twenty-four male Sprague-Dawley rats were used for (i) characterization of the HFD phenotype and (ii) evaluation of alterations following SG. Metabolic status, the degree of bladder fibrosis and tissue expression and activity of MMP2, MMP9, MMP14, TIMP1 and TIMP2 were analysed by immunohistochemistry, enzyme-linked immunosorbent assay and activity assays. Statistical differences were calculated by analysis of variance or independent Student's t-test. A P-value <0.05 was considered statistically significant. RESULTS: In HFD rats, we found significant alterations in lipid metabolism, fat mass, free fatty acid profile, insulin resistance and inflammatory markers. Voided volume was significantly decreased, and bladder showed marked fibrosis. MMPs and TIMPs were differentially regulated depending on animal status (controls, chow diet, HFD, and SG- and sham-operated animals) in both urothelium and detrusor smooth muscle. Although animal weight and most metabolic parameters were positively affected by SG, bladder fibrosis persisted. The limitations of this study were 1 month follow-up and lack of direct measurement of bladder function. CONCLUSIONS: Early diagnosis of the bladder dysfunction associated with obesity is essential to allow targeted early intervention, that is, before manifestation of potentially irreversible ECM fibrotic alterations.

Immunological monitoring of extracorporeal photopheresis after heart transplantation.

Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance-inducing effects of ECP such as up-regulation of regulatory T cells (T(regs)) are known, but specific effects of ECP on regulatory T cell (T(reg)) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of T(regs) and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of T(regs) and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of T(regs) and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4⁺CD25(high)CD127(low) T(regs) showed that CD62L-, CD120b- and CD147-positive T(regs) did not differ between the groups. CD39-positive T(regs) increased during ECP treatment compared to HTxC. ECP-treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of T(regs), pDCs and the immune balance status before and up to 12 months after starting ECP.

Invasive cardiac aspergillosis after orthotopic liver transplantation.

Invasive aspergillus infection occurs in 5 - 42 % of liver-transplanted recipients and is a dangerous complication, associated with high mortality if untreated. However, the early diagnosis of invasive aspergillosis can be elusive, as clinical signs are unspecific and the pathogenic agent is difficult to demonstrate. We here report about a 58-year-old man with acute liver failure caused by newly diagnosed chronic hepatitis B infection who underwent liver transplantation. The postoperative course was uneventful, and the patient was discharged after 30 days. After 105 days the patient was readmitted because of fever, recurrent chest and abdominal pain. Computed tomography revealed a cardiac lesion; other diagnostic steps including bone-marrow and endomycordial biopsy, virological and microbiological investigations gave no clear findings. To exclude a malignant process, thoracotomy with mass and simultaneous lower left lobe resection were performed. Histopathological findings revealed an invasive perimyocardial aspergillosis. Immediate intravenous therapy with voriconazole and caspofungin was initiated and monitoring of the mass was performed with transesophageal echocardiography and Cardio-MRI. Due to slightly increase of the lesion, medication was switched to posaconazole and caspofungin. Under this dual fungal treatment the lesion regressed and the patient could be discharged after two months in good clinical condition. Frequent Cardio-MRI scan after discharge showed further mass-regression. Therefore antifungal treatment was switched to oral posaconazole mono-therapy. After one year, complete reduction of the mass was achieved and antifungal therapy was discontinued. Recent diagnostic imaging follow-up showed no pathological finding.

Near-infrared spectroscopy monitoring of the collateral network prior to, during, and after thoracoabdominal aortic repair: a pilot study.

OBJECTIVE: The aim of this study was to evaluate the feasibility of non-invasive monitoring of the paraspinous collateral network (CN) oxygenation prior to, during, and after thoracoabdominal aortic repair in a clinical series. METHODS: Near-infrared spectroscopy optodes were positioned bilaterally-over the thoracic and lumbar paraspinous vasculature-to transcutaneously monitor muscle oxygenation of the CN in 20 patients (age: 66 ± 10 years; men = 11) between September 2010 and April 2012; 15 had open thoracoabdominal aortic repair (Crawford II and III), three had thoracic endovascular aortic repair (TEVAR; Crawford I), and two had a hybrid repair (Crawford II). CN oxygenation was continuously recorded until 48 hours postoperatively. RESULTS: Hospital mortality was 5% (n = 1), 15% suffered ischemic spinal cord injury (SCI). Mean thoracic CN oxygenation saturation was 75.5 ± 8% prior to anesthesia (=baseline) without significant variations throughout the procedure (during non-pulsatile cooling on cardiopulmonary bypass and with aortic cross-clamping; range = 70.6-79.5%). Lumbar CN oxygenation (LbS) dropped significantly after proximal aortic cross-clamping to a minimum after 11.7 ± 4 minutes (74 ± 13% of baseline), but fully recovered after restoration of pulsatile flow to 98.5% of baseline. During TEVAR, stent-graft deployment did not significantly affect LbS. Three patients developed relevant SCI (paraplegia n = 1/paraparesis n = 2). In these patients LbS reduction after aortic cross-clamping was significantly lower compared with patients who did not experience SCI (p = .041). CONCLUSIONS: Non-invasive monitoring of CN oxygenation prior to, during, and after thoracoabdominal aortic repair is feasible. Lumbar CN oxygenation levels directly respond to compromise of aortic blood circulation.

[Basic standards for a department of cardiac surgery. Quality requirements for the care of cardiac patients in connection with operations on the heart, the heart vessels and thoracic organ transplantation]. / Basisstandards einer Fachabteilung für Herzchirurgie. Qualitätsanforderungen für die Versorgung von herzkranken Patientinnen und Patienten im Zusammenhang mit Operationen/Eingriffen am Herzen, den herznahen Gefäßen und der thorakalen Organtransplantation.

Current evolutions and substantial amendments of the German health care system in combination with distinguished progress in cardiac surgery over the past years require both a reflection of principles in patient-centered care and an update of basic standard requirements for a department of cardiac surgery in Germany. In due consideration of the data from the voluntary registry of the German Society for Thoracic and Cardiovascular Surgery, this article accurately defines core requirements for a cardiac surgical department (cardiac surgery on-site), subdivided into facilities, staff and processes. If based on these standards, one may anticipate that cardiac surgical care is performed under appropriate conditions leading to an intrinsic benefit for patients.

Bypass surgery versus percutaneous coronary intervention for the treatment of unprotected left main disease. A meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis of randomized controlled trials to compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for the treatment of de novo unprotected left main disease. BACKGROUND: Although CABG is accepted to be standard of care for revascularization of unprotected left main stenosis, PCI is increasingly being used as an alternative primary approach. METHODS: We searched for randomized, controlled trials comparing CABG and PCI for the treatment of unprotected left main disease. Major adverse cardiac and cerebrovascular events (all-cause death, myocardial infarction, stroke, and repeat revascularization) were analyzed. RESULTS: The search strategy identified 4 randomized controlled trials enrolling a total of 1,611 patients. Follow-up ranged between 1 and 2 years. There were no significant differences in the risk of death or myocardial infarction between the two treatment modalities. While the risk of stroke was significantly lower in patients undergoing PCI (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.10-0.69, p = 0.007), the risk of repeat revascularization was higher among patients undergoing PCI (RR 1.94, 95% CI 1.43-2.61, p < 0.001). No relevant statistical heterogeneity across studies could be found. CONCLUSION: In this largest series of randomized patients with unprotected left main stenosis to date, the risk of death and myocardial infarction was comparable between CABG and PCI. However, patients undergoing CABG had a higher risk of stroke, whereas patients undergoing PCI were at a higher risk for repeat revascularization.

[Imaging prior to transcatheter aortic valve implantation]. / Bildgebung vor Transkatheteraortenklappenersatz.

Percutaneous transcatheter aortic valve implantation (TAVI) is an established alternative to open heart surgery in patients with severe aortic stenosis (AS) unsuitable for conventional aortic valve replacement due to comorbidities with a high perioperative risk or contraindications. Preprocedural imaging plays a major role for adequate determination of indications and prosthesis selection, prosthesis sizing and therefore for a reduction of periprocedural complications. Besides Doppler echocardiography which is mainly used for grading of the severity of aortic valve stenosis and peri-interventional imaging, cardiac computed tomography (CCT) is the imaging modality of choice. The CCT procedure not only allows for reliably assessment and measuring of the complex 3-dimensional geometry of the aortic root but also for the aorta and the peripheral vessels used as potential access paths.

Experience with anatomically orientated devices for transapical aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a new technology, which is rapidly growing to a routine procedure amenable for patients with symptomatic aortic valve stenosis and higher than average risk for conventional aortic valve surgery. The crucial disadvantage of TAVI remains the not well foreseeable risk of more than trivial degree of paravalvular leakage and a high rate of atrioventricular block and consecutive pacemaker implantation. In addition, current implantation techniques do not allow controlling the rotation of first-generation devices that might be beneficial regarding optimal physiological valve performance, optimal coronary flow and avoidance of placement of covered commissures in front of the coronary ostia. These shortcomings had pushed the development of second-generation self-expandable nitinol-based devices for subcoronary implantation that aim a reduction of paravalvular leak and AV-block by anatomical orientated positioning into the aortic root. This review focuses on the description of three different TAVI concepts, which are presently under early clinical evaluation, or have recently received commercial approval, using the transapical approach.

[Adult patients with congenital heart disease]. / Angeborene Herzfehler im Erwachsenenalter.

Unlike a few decades ago, today most patients with congenital heart disease reach adulthood after intervention or reparative surgery. As complete correction is generally not possible, a patient population with great complexity and a particular challenge to medical management is rising and a regular follow-up is mandatory. The aim of care is the timely recognition of residual or associated problems. Frequency and intensity of follow-up examinations depend on type and complexity of the lesion. The standard repertoire at follow-up consists of a specific history, clinical examination, ECG, Holter-monitoring, exercise tests, and echocardiography. Depending on the indication, cardio-MRI, CT scan, and sophisticated cardiac catheterization may become necessary. Long-term complications like rhythm disturbances, pulmonary hypertension, or heart failure are frequent, despite optimal care. Acute complications like arrhythmias, infective endocarditis, cerebral events, cerebral abscesses, aortic dissection, pulmonary embolism, and bleeding have to be recognized early and treated appropriately. Additional focus has to be placed on counseling and management of noncardiac disease and surgery, pregnancy and delivery, exercise at work and in private life, driving, and insurance issues. Training and certification of physicians as well as the establishment of specialized centers will help to ensure high quality health care for the affected patient population.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos).

Adult mallard ducks (Anas platyrhynchos) were orally dosed with bunker C fuel oil for 5 days, and five different inflammatory markers (haptoglobin, mannan-binding lectin, ceruloplasmin, unsaturated iron-binding capacity, and plasma iron) were measured in blood plasma prior to and 8, 24, 48, and 72 hr following exposure. In order to contrast the response to fuel oil with that of a systemic inflammatory response, an additional five ducks were injected intramuscularly with bacterial lipopolysaccharide (LPS). Oil-treated birds had an inflammatory marker profile that was significantly different from control and LPS-treated birds, showing decreases in mannan-binding lectin-dependent hemolysis and unsaturated iron-binding capacity, but no changes in any of the other inflammatory markers. Birds treated with oil also exhibited increased liver weights, decreased body and splenic weights, and decreased packed cell volume.

Role of CD40 ligand-mediated endothelial cell-monocyte interaction at atherosclerosis predilection sites.

BACKGROUND: Monocyte recruitment into the vessel wall at atherosclerosis predilection sites is essential for lesion development in the early phase of atherosclerosis. Platelets interacting with ultra-large von Willebrand Factor (ULVWF) multimers deposited after CD40 receptor ligation on the endothelial surface form adhesive bridges and facilitate monocyte diapedesis. We hypothesise that enhanced endothelial CD40 expression at arterial bifurcations is responsible for monocyte recruitment and that its absence reduces susceptibility to atherosclerosis. METHODS: Y-shaped channel slides covered with endothelial cells (HUVEC) and isolated perfused carotid artery bifurcations from different mouse lines were used for adhesion studies with isolated fluorescent dye-labelled platelets and monocytes. Monocyte adherence was quantified via fluorescence imaging. Oil Red O staining visualised aortic atherosclerotic plaques, and mRNA expression was determined by qRT-PCR. RESULTS: In response to soluble CD40 ligand (sCD40L) stimulated ULVWF release, the number of monocytes bound distal to the bifurcation of the Y-slide was 1.8-fold greater than without stimulation. The number of adherent monocytes in sCD40L-treated carotid artery bifurcations was 6 to 12.3-fold greater in ApoE knockout mice as compared to bifurcations derived from CD40/ApoE-deficient or control mice. CD40 mRNA expression was 2-fold higher in carotid artery bifurcations of ApoE knockout mice as compared to the proximal unbranched segment. Introduction of the CD40 knockout into the ApoE-/- background reduced the atherosclerosis burden along the entire aorta of these mice by 60 %. CONCLUSIONS: Our data demonstrate the importance of endothelial CD40 expression at atherosclerosis predilection sites for endothelial cell-platelet-monocyte interaction in the early phase of atherosclerosis.

Short-term rapamycin treatment increases life span and attenuates aortic aneurysm in a murine model of Marfan-Syndrome.

BACKGROUND: Marfan syndrome (MFS) is a genetic disorder leading to medial aortic degeneration and life-limiting dissections. To date, there is no causal prevention or therapy. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, regulating cell growth and metabolism. The mgR/mgR mice represent an accepted MFS model for studying aortic pathologies to understand the underlying molecular pathomechanisms. This study investigated whether rapamycin inhibits the development of thoracic aortic aneurysms and dissections in mgR/mgR mice. METHODS: Isolated primary aortic smooth muscle cells (mAoSMCs) from mgR/mgR mice were used for in vitro studies. Two mg kg/BW rapamycin was injected intraperitoneally daily for two weeks, beginning at 7-8 weeks of age. Mice were sacrificed 30 days post-treatment. Histopathological and immunofluorescence analyses were performed using adequate tissue specimens and techniques. Animal survival was evaluated accompanied by periodic echocardiographic examinations of the aorta. RESULTS: The protein level of the phosphorylated ribosomal protein S6 (p-RPS6), a downstream target of mTOR, was significantly increased in the aortic tissue of mgR/mgR mice. In mAoSMCs isolated from these animals, expression of mTOR, p-RPS6, tumour necrosis factor α, matrix metalloproteinase-2 and -9 was significantly suppressed by rapamycin, demonstrating its anti-inflammatory capacity. Short-term rapamycin treatment of Marfan mice was associated with delayed aneurysm formation, medial aortic elastolysis and improved survival. CONCLUSIONS: Short-term rapamycin-mediated mTOR inhibition significantly reduces aortic aneurysm formation and thus increases survival in mgR/mgR mice. Our results may offer the first causal treatment option to prevent aortic complications in MFS patients.