Ein Beitrag zur Kenntniss des Diabetes mellitus

Ohne Zusammenfassung     

Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine,captopril, CGP 37 849, and strychnine in mice

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37 849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37 849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.     

Effects of a long-distance run on cardiac markers in healthy athletes.

BACKGROUND: Running a marathon is a stressful event for athletes. Limited research exists on the role of cardiac markers during such a strenuous event. The aim of this study was to investigate detailed changes in cardiac markers before and after a long-distance run. METHODS: We studied 25 male and 2 female runners (age 34-64 years) who were running the Visé-Maastricht-Visé marathon. Blood samples were drawn just before and immediately after finishing the marathon. An additional blood sample was collected 24 h later. RESULTS: Running the marathon led to a significant increase in cortisol. This returned to baseline values 24 h after the marathon. There was a slight increase in brain natriuretic peptide (BNP); however, this was not statistically significant. On the contrary, the N-terminal fragment of BNP (NT-pro-BNP) was significantly increased immediately after the run and was normalized 24 h later in 26 out of 27 runners (96%). The magnitude of the transient elevations in BNP and NT-pro-BNP increased with the age of the athletes. Furthermore, in 9 out of 27 runners there was a significant increase in troponin T. However, in all these runners this increase was transient and troponin-T levels returned to baseline values 24 h after the marathon. CONCLUSIONS: Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage. It seems that the magnitude of the increase in BNP could serve as a marker of the biological age of the myocardium.     

Distinct effects of surgical denervation on hepatic perfusion, bowel ischemia, and oxidative stress in brain dead and living donor porcine models.

The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death.     

Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.     

Magnetic Resonance Imaging in Patients with Bone Marrow Disorders

Magnetic resonance imaging (MRI) provides a non-invasive means to evaluate a large fraction of marrow in less than one hour. Marrow disorders produce non-specific changes in marrow signal intensities which primarily reflect changes in proportions of fat and cellular elements. The pattern of these signal changes narrows the differential diagnosis, and the combination of these features with the clinical context allows interpretations which are clinically useful in many ways. These include: I) the diagnosis of avascular necrosis (and its distinction from other causes of joint pain), 2) detection of osteomyelitis, 3) differential diagnosis of hypo-plastic disorders, 4) staging of lymphomas and myeloma, 5) selection of patients for autolo-gous bone marrow transplant, 6) objective measures of marrow response to therapy, 7) detection of leukemic transformation, and 8) improved detection of marrow disease (primary or secondary) in patients with otherwise unexplained bone pain.     

Myoblast fusion in Drosophila melanogaster is mediated through a fusion-restricted myogenic-adhesive structure (FuRMAS).

During myogenesis in Drosophila embryos, a prominent adhesive structure is formed between precursor cells and fusion-competent myoblasts (fcms). Here, we show that Duf/Kirre and its interaction partners Rols7 (found in founder myoblasts and growing myotubes) and Sns (found in fcms) are organized in a ring-structure at the contact points of fcms with precursor cells, while cytoskeletal components like F-actin and Titin are centered in this ring in both cell types. The cytoplasmic protein Blow colocalizes with the actin plugs in fcms after cell adhesion. Furthermore, the requirement of additional as yet unidentified components was demonstrated by using mammalian C2C12 myoblasts. In this study, we propose that the fusion-restricted myogenic-adhesive structure (FuRMAS) is pivotal in linking cell adhesion as well as local F-actin assembly and dynamics to downstream events that ultimately lead to plasma membrane fusion. Moreover, we suggest that the FuRMAS may restrict the area of membrane breakdown.     

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.     

Hereditary cholinesterase deficiency: A report of a family with two rare genotypes

Cholinesterase deficiency was detected in a young girl following an episode of post-anesthesia apnea. Subsequently, plasma and serum cholinesterase levels and dibucaine numbers were determined on blood samples from 56 members of her extended family. Including the proband, three individuals were identified with severe cholinesterase deficiency and 12 were found to have mild abnormalities. The occurrence of two genetic variants regulating cholinesterase production, the "silent" gene and the atypical enzyme, is postulated to account for the unusual pattern of inheritance in this family. Screening family members of confirmed cases is essential to prevent the potentially fatal consequences of this hereditary disorder.