Lipapheresis: an immunoglobulin-sparing treatment for Refsum's disease

Introduction – Toxic phytanic acid concentrations in patients with Refsum's disease can be reduced by plasma separation, performed either as plasmapheresis, or as cascade filtration. The latter procedure is as efficient and safe as plasmapheresis, and eliminates the need for albumin replacement. This study investigates the loss of immunoglobulins associated with the procedure. Material and methods — Immunoglobulin- and phytanic acid serum concentrations before and after cascade filtration (n=16) were measured in a patient with Refsum's disease and their removal determined. Filters with sieving coefficients for immunoglobulin G of 70% and 30% were compared with each other and with historical data on plasmapheresis. Results — While differences in immunoglobulin M loss are negligible, the loss of immunoglobulin G in cascade filtration is significantly less than that reported for plasmapheresis and depends upon the pore size of the employed filters. The loss is least with larger pore size, but this advantage becomes statistically insignificant if immunoglobulin G loss is related to the lesser decrease in phytanic acid concentration that was achieved simultaneously in this study. Conclusion — Unless transplantation of a-hydroxylase containing tissue can be established as treatment for Refsum's disease, cascade filtration appears to be the treatment of choice in order to avoid loss of albumin and to reduce the loss of immunoglobulin G.     

Digital tourniquets: a pressure study with clinical relevance

This study measured the pressures under the three most commonly used digital tourniquets--the Penrose drain, the rolled rubber glove, and the rubber band. A miniature pressure transducer and a digital strain indicator were used to measure pressures generated by the various tourniquets. The rolled rubber glove technique was highly consistent, irrespective of the clinical experience of the subject, and uniformly generated pressures of less than 500 mm Hg. Pressures generated by Penrose drains and rubber bands were highly variable and were significantly greater than 500 mm Hg. The so-called calibrated Penrose drain generated the highest pressures in the study. The relationship between tourniquet pressures and neurovascular injury in the human digit is not clearly defined.     

Saponins from Thinouia coriacea]

The investigation of the stems of Thinouia coriacea Britton (Sapindaceae), an ichthyotoxic plant from South Brazil, afforded eight glycosides of oleanolic acid. Structures were assigned based on data from partial hydrolysis. 13C-NMR and mass spectral procedures as 3-O-alpha-L-arabinopyranoside (1), 3-O-alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranoside+ ++ (2), 3-O-beta-D-glucopyranosyl-(1----4)-alpha-L-arabinopyranoside (3), 3-O-beta-D-glucopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2 )-alpha-L-arabinopyranoside (4), 3-O-alpha-L-rhamnopyranosyl-(1----2)[beta-D-glucopyranosyl-(1----4 )]-alpha-L-arabinopyranoside (5), 3-O-beta-D-xylopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2) [beta-D-glucopyranosyl-(1----4)[alpha-L-arabinopyranoside (6), 3-O-beta-D-glucopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2 )[beta-D-glucopyranosyl-(1----4)]-alpha-L-arabinopyranoside (8). Saponin 7 showed the same sugars as 8, but the attachment between the sugars could not be elucidated. The same saponins were present in the roots, but not in the leaves.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Ueber Theilungsvorgänge in den Riesenzellen des Knochenmarkes

Ohne ZusammenfassungHierzu Taf. IV.     

Über Stoffe,die das Bindegewebswachstum zu beeinflussen vermögen

Zusammenfassung Bei der systematischen biologischen Prüfung der verschiedenen Bestandteile bestimmter ?le mineralischen Ursprungs hat sich herausgestellt, da? deren Kraft, das Wachstum des Bindegewebes anzuregen, allerwahrscheinlichst in dem Gehalte an begrenzten Mengen unges?ttigter, insbesondere partiell hydrierter Kohlenwasserstoffe zu suchen ist. Auch scheint diese Bindegewebsenergie durch Spuren h?hermolekularer basischer Stoffe in organischer Bindung und einen ebenfalls begrenzten Gehalt an bestimmten hydroxylhaltigen K?rpern etwas unterstützt zu werden. Die ?le, bei denen Bindegewebsenergie tierexperimentell festgestellt werden konnte, enthielten aber zugleich auch Stoffe, die durch übergro?e Reizung zu sch?digen vermochten und daher vor einer therapeutischen Verwendung ihres ursprünglichen Tr?gers entfernt werden mu?ten. Ein unter Verwertung dieser Erfahrungen hergestelltes Pr?parat mit durchschnittlich brauchbarstem Gehalte an Bindegewebsenergie ist das “Granulierende Wund?l-Knoll”. Die dauernde Gleichwertigkeit des Knollschen Wund?les sowie sein stetes Freisein von Nebenwirkungen wird durch biologische Kontrolle einer jeden Herstellung gew?hrleistet bleiben.     

Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.     

Short-term patient-reported outcomes after different exercise-based cardiac rehabilitation programmes.

BACKGROUND: An objective of exercise-based cardiac rehabilitation is improvement in patient-reported outcomes such as health-related quality of life as well as anxiety and depressive symptoms. There are no direct comparisons of the effectiveness of inpatient and outpatient exercise-based cardiac rehabilitation programmes on patient-reported outcomes. METHODS: In this non-randomized study we collected patient-reported outcomes data with the MacNew Heart Disease health-related quality of life questionnaire and the Hospital Anxiety and Depression Scale at baseline, 1 month and again 3 months after admission to exercise-based cardiac rehabilitation in a cohort of 216 consecutive patients enrolled either in a 4-week inpatient exercise-based cardiac rehabilitation (n=62) or a 3-month outpatient exercise-based cardiac rehabilitation (n=87) and in a usual care group (n=67) to document the natural course in patient-reported outcome variables without exercise-based cardiac rehabilitation. RESULTS: Although MacNew health-related quality of life scores improved more with inpatient than outpatient exercise-based cardiac rehabilitation by month 1, the improvement was still significant in both groups at month 3 and also in the usual care group when compared to baseline. The health-related quality of life scores in the inpatient group, however, decreased between month 1 and 3 whereas they continued to improve in the outpatient group. The significant reduction in both anxiety and depressive symptoms in both exercise-based cardiac rehabilitation groups by month 1 was maintained at month 3 only with outpatient exercise-based cardiac rehabilitation. No significant changes over the 3 months were observed in the usual care group. CONCLUSION: Significant improvements of 1-month patient-reported outcomes are achieved in patients attending inpatient as well as outpatient exercise-based cardiac rehabilitation when compared with no exercise-based cardiac rehabilitation. In contrast to inpatient exercise-based cardiac rehabilitation, however, outpatient exercise-based cardiac rehabilitation leads to a further improvement of patient-reported outcomes. These results suggest that, if patients have to be admitted for inpatient exercise-based cardiac rehabilitation, this programme should be followed by an outpatient exercise-based cardiac rehabilitation to further improve and stabilize these patient-reported outcome variables.     

Thermal and cold neutron phase-contrast radiography.

In this paper, we will discuss a phase-contrast imaging method that avoids the complications of interferometry to provide phase contrast in weakly absorbing samples. A transversely coherent neutron beam is used with the traditional radiography scheme. Images taken with this scheme show dramatic intensity variations due to sharp changes in the neutron wave refractive index. With some numerical processing these images may be used to reconstruct a quantitative phase radiograph of specimens imaged with this technique.