Promotion of fracture healing by vitamin E in rats

We investigated the effects of the antioxidant alphae-tocopherol on early- and late-phase fracture healing in a rat model. Sixty male Sprague-Dawley rats were randomized into two groups. The right tibia of each rat was fractured manually under anaesthesia, and fracture sites fixed with intramedullary Kirschner wires. The alpha-tocopherol group received 20 mg/kg alpha-tocopherol intraperitoneally; the control group received intraperitoneal saline injections. Ten rats from each group were sacrificed on day 15, day 45 and day 60. In the alpha-tocopherol group, malondialdehyde concentrations, a measure of lipid peroxidation associated with oxygen free radicals, were significantly decreased on day 15 and day 45 compared with the control group, but had regained the 15-day value on day 60. On histopathological and radiological assessment, fracture healing on day 60 was significantly more advanced in the alpha-tocopherol group. We conclude that alpha-tocopherol has a positive effect on both early and late-phase fracture healing, and may be beneficial in clinical fracture     

Folate-conjugated liposomes preferentially target macrophages associated with ovarian carcinoma

The folate receptor (FR) is overexpressed on many epithelial cancers and has been exploited for targeted delivery of folate-linked liposomes to cancer cells in vitro. The present studies investigate the distribution of folate-targeted liposomes in a FR(+) mouse model of ovarian cancer. According to flow cytometric analysis, folate-conjugation of liposomes significantly enhanced their uptake into ovarian cancer cells and tumor-associated macrophages within tumor ascites fluid. Compared to ovarian cancer cells, macrophages acquired tenfold more liposomes, and approximately 50% of this uptake was FR-dependent. These results demonstrate that, in addition to their cancer cell-targeting properties, folate-liposomes may be useful for targeting drugs to tumor-associated macrophages in vivo.     

HIV type 1 BF recombinant strains exhibit different pol gene mosaic patterns: descriptive analysis from 284 patients under treatment failure

Different complex structures of the pol gene have been identified in 284 HIV-1 B/F recombinant sequences obtained from a group of 587 patients under treatment failure from Argentina. To analyze the mosaic structures of these viral sequences and to determine their phylogenetic relationship, the 284 partial pol gene sequences of BF recombinant viruses were amplified by RT-PCR and sequenced. Intersubtype breakpoints were analyzed by bootscanning. Phylogenetic relationships were determined by means of neighbor-joining trees. The analysis of the sequences showed multiple phylogenetic topologies clustering within intersubtype BF reference sequences. At least three different mosaic patterns were found compared to previously described BF-type viruses with unequal distribution in the studied population. The analysis also showed that HIV-1 BF recombinant viruses with diverse mosaic structures are phylogenetically related in their F segments and in selected B fragments with the F1 subtype and with BF recombinant viruses from Brazil, respectively, suggesting a common recombinant ancestor. No association was observed between the prevalence of each mosaic pattern and the frequency of major drug-resistance mutations in PR and RT.     

The path from initial inquiry to initiation of treatment for social anxiety disorder in an anxiety disorders specialty clinic

Efficacious treatments for social anxiety disorder have become increasingly available, with approximately three-quarters of treatment completers showing significant improvement [Arch. Gen. Psychiatry 55 (1998) 1133.]. However, very few individuals with social anxiety disorder access these services. The present study reports on the path to initiation of treatment for social anxiety disorder among individuals contacting an anxiety disorder specialty clinic. Of 395 initial telephone inquiries, only 60 individuals (15%) started treatment. Three "critical points" associated with high pretreatment attrition were identified: scheduling an initial interview, attending a scheduled initial interview, and initiating a treatment program after receiving a principal diagnosis of social anxiety disorder. Several demographic variables (e.g., level of education, race) were related to attendance at the initial interview. However, no differences were found between those who did and did not initiate treatment on demographic variables, symptom severity, or quality of life. Given that most individuals who complete treatment for social phobia experience significant benefit, results of the current study suggest that future efforts should be devoted to increasing number of patients who access these services.     

Cysteine cathepsins (proteases)--on the main stage of cancer?

Cysteine cathepsins are involved in degradation of extracellular matrix, facilitating growth, invasion, and metastasis of tumor cells, in tumor angiogenesis, in apoptosis, and in events of inflammatory and immune responses. In this issue of Cancer Cell, demonstrate association of increased cathepsins activity with angiogenic vasculature and invasive fronts of carcinomas during tumorigenesis in transgenic mouse models using activity-based chemical probes and in vivo imaging. Moreover, this study shows that a broad-spectrum cysteine cathepsin inhibitor effectively blocks several stages of tumorigenesis in the RIP1-Tag2 transgenic mouse model, offering new therapeutic opportunities in cancer treatment.     

Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity

Cancer cells express self-antigens that are weakly recognized by the immune system. Even though responses against autologous cells are difficult to induce, the immune system is still able to mount a response against cancer. The discovery of the molecular identity of antigens that are recognized by the immune system of melanoma patients has led to the elucidation of tumor immunity at a cellular and molecular level. Multiple pathways in both the priming and effector phases of melanoma rejection have been described. Animal models' active immunotherapies for melanoma show a requirement for the cellular compartment of the immune system in the priming phase, primarily CD4+T cells. More diverse elements are required for the effector phase, including components from the innate immune system (macrophages, complement and/or natural killer cells) and from the adaptive immune system (CD8+T cells and B cells). Minor differences in amino-acid sequences of antigens must determine the particular mechanisms involved in tumor rejection. Since the immune system contains T and B cells that recognize and reject autologous cells, a consequence of tumor immunity is potential autoimmunity. There are distinct pathways for tumor immunity and autoimmunity. The requirements for autoimmunity at the priming phase seem to be CD4+/IFN-gamma dependent while the effector mechanisms are alternative and redundant. Vitiligo (autoimmune hypopigmentation) can be mediated by T cells, FcgammaR+macrophages and/or complement.     

Rectal cancer in Luxembourg : a national population-based data report, 1988–1998

Background  

Morphologic criteria which might help to support the need for a preventive strategy for early detection of rectal cancer were analysed. Population-based data on rectal adenomas with high-grade dysplastic changes (n = 199) and invasive adenocarcinomas (n = 912) registered by the national Morphologic Tumour Registry (MTR) and diagnosed in a central department of pathology in Luxembourg between 1988 and 1998 were considered.