Linitis plástica primaria rectal

Primary linitis plastica of the rectum is an infrequent and unusual rectal carcinoma. We report a new case that presented clinically as a haemorrhoidal syndrome. We comment on the characteristics--clinical picture and histopathology--of this uncommon presentation of rectal tumour, as well as its clinical history and prognosis taking into account that the literature consulted indicated the unusualness of primary linitis plastica of the rectum.     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.     

Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage.

Adipose tissue represents an accessible source of mesenchymal stem cells (ADSCs), with similar characteristics to bone marrow-derived stem cells. The aim of this work was to investigate the transdifferentiation of ADSCs into hepatic lineage cells in vitro. ADSCs were obtained from human adipose tissue from lipectomy. Cells were grown in medium containing 15% AB human serum. Cultures were serum deprived for two days and exposed to a two-step protocol with two different media using growth factors and cytokines. Hepatic differentiation was assessed by RT-PCR of liver-marker genes. ADSCs exhibited a fibroblastic morphology that changed to a cuboidal shape when cells differentiated. Expression of liver genes increased when using one of the two studied media consisting of DMEM supplemented with HGF, bFGF and nicotinamide for 14 days. The results indicate that, under certain specific inducing conditions, ADSCs can be induced to differentiate into hepatic lineage in vitro. Adipose tissue may be an ideal source of high amounts of autologous stem cells.     

What role does gemtuzumab ozogamicin have in the treatment of acute myelogenous leukemia?

Gemtuzumab ozogamicin (GO) is a novel, targeted chemotherapy designed to treat acute myeloid leukemia (AML). GO consists of an antitumor antibiotic, calicheamicin, linked to a humanized monoclonal antibody against CD33. It has been approved in the United States since 2000 to treat CD33+ AML in first relapse in older adults who are not candidates for cytotoxic therapy. Beyond this indication, the role of GO is evolving. Single-agent GO has a limited role in de novo AML. Incorporation of GO into standard induction treatment in de novo and relapsed AML is feasible. Comparative phase III studies of such an approach are ongoing. GO is associated with serious toxicities, such as infusional reactions, transient liver function test abnormalities, and veno-occlusive disease of the liver, especially in patients who undergo hematopoietic stem cell transplantation.     

Occupational asthma in bakeries caused by sensitivity to α-amylase

We report on a patient with asthma induced by occupational exposure to alpha-amylase derived from Aspergillus oryzae, which is a component of bread additives. A type I hypersensitivity to this enzyme was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an alpha-amylase extract.