Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Combined differentiating therapy for myelodysplastic syndromes: a phase II study

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.     

Low temperature delamination of plastic encapsulated microcircuits

Plastic encapsulated microcircuits (PEMs) are increasingly being used in applications requiring operation at temperatures lower than the manufacturer’s recommended minimum temperature, which is 0°C for commercial grade components and −40°C for industrial and automotive grade components. To characterize the susceptibility of PEMs to delamination at these extreme low temperatures, packages with different geometries, encapsulated in both biphenyl and novolac molding compounds, were subjected to up to 500 thermal cycles with minimum temperatures in the range −40 to −65°C in both the moisture saturated and baked conditions. Scanning acoustic microscopy revealed there was a negligible increase in delamination at the die-to-encapsulant interface after thermal cycling for the 84 lead PQFPs encapsulated in novolac and for both 84 lead PQFPs and 14 lead PDIPs encapsulated in biphenyl molding compound. Only the 14 lead novolac PDIPs exhibited increased delamination. Moisture exposure had a significant effect on the creation of additional delamination.     

Use of the polymerase chain reaction in the diagnosis of leprosy

A case is described in which a pericardial branch of a nongrafted left internal mammary artery communicated directly with the distal left anterior descending artery, following saphenous vein bypass grafting. This type of collateralization following coronary artery bypass surgery seems to be very rare, and perhaps could protect the myocardium from severe ischemia.     

On the Use of the Flickermeter to Limit Low-Frequency Interharmonic Voltages

The possibility of using the IEC flickermeter for the assessment of the limits of low frequency interharmonic voltages is critically analyzed. The response of flickermeters to interharmonic components is analytically investigated, obtaining approximation formulas for the calculation of Pst in the presence of couples of components at frequencies that are symmetric with reference to the fundamental and in the presence of one or more single components. The instrument characteristics and limitations are also highlighted, using the results obtained from a numerical implementation of the IEC flickermeter. Finally, the general problem of the limits of low frequency interharmonic voltages is discussed and practical solutions are proposed.     

EGF/EGF-R system and benign breast disease during and following the treatment of gynaecological pathologies with an analogue of LH-RH

Clinical and pathological changes of the mammary gland have been studied in 64 women affected by symptomatic Benign Breast Disease (BBD) coexisting with endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They were evaluated clinically and ultrasonographically before and after treatment to find possible changes of BBD as well as of endometriosis or uterine leiomyomata. Mammary biopsies were performed before and after treatment in all the patients to study the changes of EGF-R expression. Results showed that clinical improvement is accompanied with a reduction of EGF-R expression.     

Heart arrest during dipyridamole scintigraphy: report of 3 cases

Potentially life threatening rythm disturbances, such as third degree A-V block and sinus arrest without "escape rythm", represent infrequent and unexpected events during dipyridamole thallium scintigraphy. We report three cases of cardiac arrest requiring resuscitation maneuvers after dipyridamole infusion during myocardial thallium scan. On the basis of these clinical observations we suggest that a trained cardiologist and resuscitation kit should be available in nuclear lab. Moreover elderly patients may require careful screening for preexisting conduction defects and sick sinus syndrome. When dipyridamole infusion provokes severe bradyarrhythmias not related to myocardial ischemia, a transesophageal electrophysiological study should always be performed.     

Proteomics integrated with Escherichia coli vector-based vaccines and antigen microarrays reveals the immunogenicity of a surface sialidase-like protein of Propionibacterium acnes

Proteomics is a powerful tool for the identification of proteins, which provides a basis for rational vaccine design. However, it is still a highly technical and time‐consuming task to examine a protein's immunogenicity utilizing traditional approaches. Here, we present a platform for effectively evaluating protein immunogenicity and antibody detection. A tetanus toxin C fragment (Tet‐c) was used as a representative antigen to establish this platform. A cell wall‐anchoring sialidase‐like protein (SLP) of Propionibacterium acnes was utilized to assess the efficacy of this platform. We constructed an Escherichia coli vector‐based vaccine by overexpressing Tet‐c or SLP in E. coli and utilized an intact particle of E. coli itself as a vaccine (E. coli Tet‐c or SLP vector). After ultraviolet (UV) irradiation, the E. coli vector‐based vaccines were administered intranasally into imprinting control region mice without adding exogenous adjuvants. For antibody detection, we fabricated antigen microarrays by printing with purified recombinant proteins including Tet‐c and SLP. Our results demonstrated that detectable antibodies were elicited in mice 6 weeks after intranasal administration of UV‐irradiated E. coli vector‐based vaccines. The antibody production of Tet‐c and SLP was significantly elevated after boosting. Notably, the platform with main benefits of using E. coli itself as a vaccine carrier provides a critical template for applied proteomics aimed at screening novel vaccine targets. In addition, the novel immunogenic SLP potentially serves as an antigen candidate for the development of vaccines targeting P. acnes‐associated diseases.