Resorptions- und Sekretionsprüfungen bei Perfusion des Rattendarms mit hypo- und hypertonischen Glucoselösungen

Ohne Zusammenfassung     

The Kallikrein-Kinin system and muscle metabolism—Clinical aspects

The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients.     

CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition

We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based vaccines in nine HIV-1 seronegative vaccine recipients with regard to their patterns of HLA restriction and epitope recognition. We found that seven of nine volunteers developed detectable CTL reactivities against novel epitopes within the HIV-1 Env and Gag proteins. Although four of nine subjects were HLA-A*0201, none of the cellular responses was restricted in the context of this allele. The type of responses observed in this sampling of vaccines appeared similar to those reported during primary infection and among long term non-progressors, with three out of nine subjects recognizing HLA-B27 or HLA-B17(57)-restricted epitopes. Although the majority of CTL responses were directed against novel epitopes, these effectors were still able to mediate cross-clade reactivities.     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

Exposure to epididymal extracellular vesicles enhances immature sperm function and sustains vitality of cryopreserved spermatozoa in the domestic cat model

Journal of Assisted Reproduction and Genetics - Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer key factors to maturing spermatozoa. Using an in vitro system previously...     

Effects of Androgen Disruption by DDE on the Development and Functioning of the Immune System in Japanese Quail

We hypothesized that immunosuppression in birds that is caused by exposure to antiandrogenic chemicals occurs mainly through disruption of the development of the androgen-sensitive avian lymphoid organ, the bursa of Fabricius. Injections of 20.0 or 40.0 μg of p,p′-DDE [ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)], an antiandrogen, were administered at embryonic day 1. Bursas from only chicks treated with DDE were larger than, had fewer follicles, and exhibited vacuolization within follicles compared with controls; spleens were unaffected. No differences in either immune response test were observed. This study demonstrates that the bursa may play a role in androgen-active endocrine disrupting chemical-induced immunosuppression.     

Short term suppression of follicular recruitment and spontaneous ovulation in the cat using levonorgestrel versus a GnRH antagonist

Suppression and subsequent rebound of ovarian activity using a progestin (levonorgestrel; Norplant) versus a GnRH antagonist (antide) was assessed in the domestic cat via fecal estradiol and progesterone metabolite analyses. Following an initial dose-response trial, queens were assigned to one of four treatments: (1) antide, two 6 mg/kg injections 15 days apart (n = 8 cats); (2) levonorgestrel, six silastic rods (36 mg levonorgestrel/rod) implanted for 30 days (n = 8); (3) control injections (n = 5); and (4) control implants (n = 5). Steroid metabolites were quantified from daily fecal samples for 90 days before, 30 days during, and 90 days after treatment. Antide and levonorgestrel inhibited estrous cyclicity in contrast to continued cyclicity in controls. Cats already at estradiol baseline in antide (n = 7) and levonorgestrel (n = 4) groups remained inhibited during treatment. In females with elevated estradiol levels at treatment onset (Day 0), a normal estradiol surge was completed before concentrations declined to baseline (∼Days 5-7) and remained suppressed throughout the remaining treatment period. Additionally, 56% of treatment animals exhibited at least one spontaneous ovulation during the pre-treatment period, but no female ovulated during treatment with levonorgestrel or antide. Antide-treated cats exhibited lower (P < 0.05) baseline estradiol concentrations during treatment compared to pre- and post-treatment. In contrast, levonorgestrel induced elevations in baseline estradiol following treatment compared to pre- and during treatment intervals. Control females showed no change (P > 0.05) in baseline estradiol throughout the study period. All levonorgestrel and antide cats returned to estrus after treatment withdrawal. Results demonstrate that: (1) both antide and levonorgestrel are effective for inducing short-term suppression of follicular recruitment and ovulation in the cat; (2) inhibition is reversible; and (3) GnRH antagonists and progestins differentially regulate basal estradiol secretion. This study also confirmed a relatively high incidence of spontaneous ovulation in the cat, a species generally considered to be an induced ovulator.     

Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia

Atypical chronic myeloid leukemia (aCML) occurs rarely and is associated with a poor prognosis when treated with conventional chemotherapy. We evaluated the outcome of aCML after allogeneic hematopoietic stem cell transplantation (HSCT). Nine patients were transplanted from HLA-identical siblings (n = 4), HLA-compatible unrelated donors (n = 4) or twin brother (n = 1). Median follow-up was 55 months after transplant (range, 9.1-118.1 months). One patient who was transplanted in advanced disease with bone marrow from his twin brother relapsed 19 months post transplant. This patient was successfully retransplanted from the original donor. All patients remained in complete remission. Analysis of the leukocyte chimerism of peripheral white blood cells and bone marrow buffy coat cells by VNTR-polymerase chain reaction (PCR) and single-nucleotide polymorphism real-time PCR revealed complete chimerism in all patients who had received an allogeneic transplant. One patient suffering from cerebral toxoplasmosis died 9 months post transplant. All other patients were alive at the time of analysis. Our findings suggest that the outcome of allogeneic or syngeneic transplantation in patients with aCML may not be worse than the outcome of transplantation for BCR-ABL-positive CML.