Über Die SystematIk von 18 aus verschiedenen Krankheitsprozessen der menschlichen Haut gewonnenen Sprosspilzen

Ohne ZusammenfassungD 5.Bei Vollendung meiner Arbeit möchte ich meinem sehr verehrten Lehrer, Herrn Prof. Dr.Grütz, Direktor der Dermatologischen Universitätsklinik Bonn, meinen besten Dank aussprechen für die überlassung des Themas und seinen mir jederzeit freundlich gewährten Rat.     

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

Nicotinamide riboside, an NAD⁺ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD⁺ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.     

Translumbar retroperitoneal endoscopy: an alternative in the follow-up and management of drained infected pancreatic necrosis

BACKGROUND: The follow-up of drained infected pancreatic necrosis (IPN) is usually done with data on the patient's clinical evolution and information obtained from serial helical computed tomographic scans. Management often requires necrosectomies and periodic debridements. HYPOTHESIS: Translumbar retroperitoneal endoscopy is effective in the management of drained IPN. DESIGN: A prospective observational study. SETTING: University tertiary care hospital. PATIENTS: A series of 11 consecutive patients with drained IPN undergoing postoperative follow-up with translumbar retroperitoneal endoscopy. INTERVENTIONS: Initially, the IPN was drained via the posterior extraperitoneal translumbar approach; then, a superficial necrosectomy was performed during the same surgical intervention by flushing and endoscopic aspiration; and, finally, a lavage and drainage system was fitted. In the immediate postoperative period, for management of the IPN, we removed the drainage tube and inserted a flexible endoscope as far as the pancreatic area to eliminate the infected necrotic material by flushing and aspiration. MAIN OUTCOME MEASURES: In these patients, we studied control of the infection of the pancreatic area, quantification variables of the necrosectomy, technique-related morbidity and mortality, and the need for subsequent operations. RESULTS: The 11 patients studied showed good results regarding the control and complete elimination of the infected necrosis. There was no technique-related morbidity or mortality or need for subsequent operations. CONCLUSION: Translumbar retroperitoneal endoscopy allows exploration of the retroperitoneal space under direct visual guidance, facilitates lavage and aspiration, avoids subsequent surgical operations for debridement, decreases the need for repeated computed tomographic scans to evaluate the evolution of the IPN, and has no added morbidity or mortality.     

Efectividad y seguridad de la terapia de rescate en pacientes VIH

IntroductionThe treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen.Patients and methodsHIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed.ResultsThere were 28 patients studied, with an average of 10 treatment regimens prior to starting salvage therapy (SD = 3.5; 95 % CI, 8.9-11.1). A total of 85.7 % patients had treatment adherence > 90 %. For ENF, 70.8 % of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) < 400 copies/ml doubled, and cases with undetectable CV (< 50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia.ConclusionsThe salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness.     

Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

Some properties of marrow derived adherent cells in tissue culture

It has previously been shown that monolayer cultures derived adherent cells (MDAC), apparently consisting of fibroblasts, macrophages, epithelioid cells, and fat cells, can support long-term stem cell proliferation in vitro. In the present study, the hematopoietic support capability of murine MDAC monolayers was confirmed and the cultured cells further characterized with respect to the following properties: esterase I activity, complement (C3) receptors, IgG (Fc) receptors, colony stimulating activity (csa) production, and collagen synthesis. The cultures were also examined immunohistochemically to localize fibronectin, laminin, and collagen synthesis and to identify the collagen subtypes synthesized. MDAC morphology was as described in previous studies, although fat cells were few in number. It was found that MDAC included some cells with esterase I activity and C3 receptors. Fc receptors were not, however, detected, nor did the cultures produce csa, indicating that mononuclear phagocytes were not present. MDAC synthesized collagen types I and III and also fibronectin. Staining for epithelial basement membrane proteins (collagen types IV and V and laminin) was negative. The results indicate that the vast majority of these cultured MDAC were fibroblasts.     

Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene

Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals.