Microemulsion for Intradermal Delivery Of Cetyl Alcohol and Octyl Dimethyl PABA

A water-in-oil microemulsion was prepared to deliver cetyl alchohol [I] octyl dimethyl PABA or Padimate-O [II] in vitro using human and hairless mouse skin. A standard Franz diffusion cell and a microsectiong cryostat microtome were used to quantify the rate and the depth of penetration and the results were compared in the percent does penetrated for this microemulsion and two macroemulsion formulations, namely a cream and a lotion. It appeared that the microemulsion had the ability to deliver [I] into the skin 2-6 times faster and at least twice as much as that with the other two formulations. Furthermore, the absorption of [I] from the cream or lotion product could bel enhanced by as much as 50-250% if the skin had been pretreated with microemulsion prior to product application. The advantage of using a microemulison to acheieve deeper and faster penetratin of the permeating compunds was clearly demonstreated in this study.     

Effect of temperature on stresses and delamination failure of z-pinned joints

Although z-pins have been shown effective in preventing delaminations in adhesively bonded and co-cured joints, their applicability depends on a reliable assessment of the strength of a z-pin-composite assembly. In particular, high residual thermal stresses that have been found in experiments dictate the necessity in a local stress analysis. Elevated temperature applied to the joint during its lifetime may also affect its effectiveness in preventing delaminations. The present paper illustrates an approach to determining local residual stresses confirming the observations regarding a possible delamination and cracking in the composite structure due to high post-processing transverse stresses. The analysis of the effect of elevated temperature applied at one of the surfaces on the response of a z-pinned joint is conducted using the concept of a double cantilever beam with an “insulated” crack. In addition, it is illustrated that an elevated temperature may actually benefit the integrity of the joint if it causes an increase in the z-pin-composite interfacial strength.     

Stress increases the population of splenic macrophages, permissive for Langat virus, in mice

Cytogenetic study conducted after a single intraperitoneal injection of cyclophosphane in doses of 10, 20, and 40 mg/kg showed in 1.5-2-month-old male mice that the level of bone marrow cells damaged by the mutagen was significantly higher in NZW animals than in C57Bl/6 animals. The ability to produce active oxygen forms in response to addition of opsonized zymosan and phorbol myristate acetate was also higher in bone marrow suspensions of NZW mice. The higher sensitivity of NZW animals to pro-oxidant and clastogenic effects may be related to the genetically determined decrease of antioxidant protection in NZW animals.     

Unusual immunocytochemical and ultrastructural features of synovial fluid cells in multicentric reticulohistiocytosis. A case report

We present the first report in which cells in synovial fluid from a patient with multicentric reticulohistiocytosis (MRH) were studied by immunocytochemistry for correlation with routine light and electron microscopy. MRH cells stained predominantly for lymphocyte-related surface antigens and not for the monocyte marker LEU M3 (CD14). These findings suggest a lymphocytic origin of MRH cells and not a histiocytic origin, as previously suggested. In addition, large numbers of membrane-bound, electron-dense, secretory-type granules were found ultrastructurally in the cytoplasm of these cells.     

Dissecting the order of bacteriophage T4 DNA polymerase holoenzyme assembly

Most biological organisms rely upon a DNA polymerase holoenzyme for processive DNA replication. The bacteriophage T4 DNA polymerase holoenzyme is composed of the polymerase enzyme and a clamp protein (the 45 protein), which functions as a processivity factor by strengthening the interaction between DNA and the holoenzyme. The 45 protein must be loaded onto DNA by a clamp loader ATPase complex (the 44/62 complex). In this paper, the order of events leading to holoenzyme formation is investigated using a combination of rapid-quench and stopped-flow fluorescence spectroscopy kinetic methods. A rapid-quench strand displacement assay in which the order of holoenzyme component addition is varied provided data indicating that the rate-limiting step in holoenzyme assembly is associated with the clamp loading process. Pre-steady-state analysis of the clamp loader ATPase activity demonstrated that the four bound ATP molecules are hydrolyzed stepwise during the clamp loading process in groups of two. Clamp loading was examined with stopped-flow fluorescence spectroscopy from the perspective of the clamp itself, using a site-specific, fluorescently labeled 45 protein. A mechanism for T4 DNA polymerase holoenzyme assembly is proposed in which the 45 protein interacts with the 44/62 complex leading to the hydrolysis of 2 equiv of ATP, and upon contacting DNA, the remaining two ATP molecules bound to the 44/62 complex are hydrolyzed. Once all four ATP molecules are hydrolyzed, the 45 protein is poised on DNA for association with the polymerase to form the holoenzyme.     

Diagnosis and therapy of chronic polyarthritis

Rheumatoid arthritis (RA) is the most frequent inflammatory joint disease, and it affects about 1% of the population. The onset of arthritis is rarely acute; it is subacute and usually progresses slowly. The clinical picture of RA is variable: mild to very aggressive and destructive courses, sometimes accompanied by organ involvement, leading to severe functional impairment and early disability can be observed. RA is diagnosed according to the ACR criteria published in 1958 and modified in 1988. The appearance of a palpable joint swelling or effusion is obligatory for the clinical diagnosis of arthritis. In RA, typically involvement of the joint of the hands and feet can be seen. Laboratory parameters play an important role as both diagnostic and prognostic tools. Besides clinical features and laboratory parameters, imaging techniques provide another cornerstone in the diagnosis of RA. Until now plain X-rays, which primarily visualize osseous changes, are the most important technique in daily practice, whereas magnetic resonance imaging and ultrasound may provide information about soft tissue changes in an earlier stage of disease. The main differential diagnoses of RA to be considered are the seronegative spondylarthropathies (psoriatic arthritis, arthritides accompanying inflammatory bowel diseases, Reiter's syndrome, and spondylitis ankylosans with peripheral arthritis), Parvovirus-induced arthritis, crystal-induced arthritides and septic arthritis. Early diagnosis and therapeutic intervention seem to be of great prognostic importance. In several independently performed investigations a higher mortality was found in RA patients than in the normal population. Drug therapy of RA consists of nonsteroidal antirheumatic drugs (NSAIDs), corticosteroids and disease-modifying drugs (DMARDs). When the functional and radiological parameters were assessed, the DMARDs were found to have a disease modifying and in rare cases a remission-inducing property. Moreover, tolerance these to drugs is limited. Newer therapeutic trials have employed substances like Tenidap, Leflunomid, bacterial extracts, antibiotics and biological subcomes (e.g., monoclonal antibodies against cytokines, fusion proteins for soluble cytokinereceptors). Some promising results of these investigations need confirmation in larger patient populations, but some new perspectives for a more efficacious treatment of RA can be expected.