In Silico Study of Novel Cyclodextrin Inclusion Complexes of Polycaprolactone and Its Correlation with Skin Regeneration.

Three novel biomaterials obtained via inclusion complexes of ß-cyclodextrin, 6-deoxi-6-amino-ß-cyclodextrin and epithelial growth factor grafted to 6-deoxi-6-amino-ß-cyclodextrin with polycaprolactone. Furthermore, some physicochemical, toxicological and absorption properties were predicted using bioinformatics tools. The electronic, geometrical and spectroscopical calculated properties agree with the properties obtained via experimental methods, explaining the behaviors observed in each case. The interaction energy was obtained, and its values were -60.6, -20.9 and -17.1 kcal/mol for ß-cyclodextrin/polycaprolactone followed by the 6-amino-ß-cyclodextrin-polycaprolactone complex and finally the complex of epithelial growth factor anchored to 6-deoxy-6-amino-ß-cyclodextrin/polycaprolactone. Additionally, the dipolar moments were calculated, achieving values of 3.2688, 5.9249 and 5.0998 Debye, respectively, and in addition the experimental wettability behavior of the studied materials has also been explained. It is important to note that the toxicological predictions suggested no mutagenic, tumorigenic or reproductive effects; moreover, an anti-inflammatory effect has been shown. Finally, the improvement in the cicatricial effect of the novel materials has been conveniently explained by comparing the poly-caprolactone data obtained in the experimental assessments.

A Portable Fuzzy Driver Drowsiness Estimation System.

The adequate automatic detection of driver fatigue is a very valuable approach for the prevention of traffic accidents. Devices that can determine drowsiness conditions accurately must inherently be portable, adaptable to different vehicles and drivers, and robust to conditions such as illumination changes or visual occlusion. With the advent of a new generation of computationally powerful embedded systems such as the Raspberry Pi, a new category of real-time and low-cost portable drowsiness detection systems could become standard tools. Usually, the proposed solutions using this platform are limited to the definition of thresholds for some defined drowsiness indicator or the application of computationally expensive classification models that limits their use in real-time. In this research, we propose the development of a new portable, low-cost, accurate, and robust drowsiness recognition device. The proposed device combines complementary drowsiness measures derived from a temporal window of eyes (PERCLOS, ECD) and mouth (AOT) states through a fuzzy inference system deployed in a Raspberry Pi with the capability of real-time response. The system provides three degrees of drowsiness (Low-Normal State, Medium-Drowsy State, and High-Severe Drowsiness State), and was assessed in terms of its computational performance and efficiency, resulting in a significant accuracy of 95.5% in state recognition that demonstrates the feasibility of the approach.

Phase 2 trial of Allovectin-7 in advanced metastatic melanoma.

Treatment of metastatic melanoma with chemotherapeutic regimens has led to disappointing response rates, duration of response and no appreciable impact on survival. Intralesional injection of a low dose of an HLA-B7/beta2 microglobulin plasmid formulated with cationic lipids (Allovectin-7 is a registered trademark of Vical, Incorporated, San Diego, California, USA) has been shown previously to be safe and well tolerated. A phase 2, open-label study was performed at 16 centers in the United States. Seventy-seven patients were treated with 10 mug intralesional Allovectin-7 weekly for 6 weeks and clinical response to treatment were evaluated by World Health Organization criteria. Minimal adverse events were associated with the Allovectin-7 injections. Seven patients (9.1%) had complete or partial response with 4.8 months median duration of response. Allovectin-7 was shown to be safe and exhibit biological activity at this dose. Its safety profile may enable Allovectin-7 to be used at higher doses, which may provide greater clinical activity.

Efficacy and safety of HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex (Allovectin-7) in patients with metastatic melanoma.

Human leukocyte antigen (HLA)-B7/beta-2 microglobulin plasmid DNA/lipid complex, otherwise known as Allovectin-7 (Vical, Inc., San Diego, CA, USA), has been developed as a non-viral gene delivery product. After multiple laboratory and human trials, it appears that the concept of gene transfer has established itself as a clinical reality. While the manifestations of the gene transfer have not been as dramatic as one might have hoped, HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex appears to be a promising agent with an extremely safe toxicity profile. Ongoing trials are further investigating potential clinical uses of Allovectin-7.

High-dose vincristine sulfate liposome injection (Marqibo) Is not associated with clinically meaningful hematologic toxicity.

BACKGROUND: Vincristine sulfate liposome injection (VSLI) facilitates vincristine dose intensification and densification, is active in untreated and relapsed lymphoma, and has been approved in the United States for relapsed and refractory acute lymphoblastic leukemia. Cancer- and concomitant chemotherapy-related anemia, neutropenia, and thrombocytopenia in patients with hematologic malignancy have complicated the evaluation of hematologic toxicity related to new drugs. PATIENTS AND METHODS: We assessed the hematologic toxicity of VSLI 2.25 mg/m(2) administered every 14 (cohort 1) or 7 (cohort 2) days in 54 patients with metastatic uveal melanoma, a cancer not known to involve the bone marrow. RESULTS: Cohort 2 received a greater median number of VSLI doses (6 vs. 4) within a shorter median period (5.7 vs. 8.7 weeks), resulting in a larger median cumulative exposure (22.6 vs. 17.7 mg) and near doubling of the median dose density (2.2 vs. 4.0 mg/wk) compared with cohort 1. Despite greater VSLI exposure and dose density, cohort 2 had a lower median decrease from baseline in the neutrophil count and a greater increase from baseline in the platelet count compared with cohort 1. Hematologic adverse events (AEs) were uncommon and mostly grade 1 or 2 in severity. No grade 4 hematologic AEs developed. CONCLUSION: VSLI at its approved dose resulted in a low incidence of clinically meaningful hematologic toxicity. A near doubling of the median dose density did not have an identifiable effect on the reported incidence and severity of hematologic AEs. VSLI could be well suited for use combined with myelosuppresive drugs and for patients unable to tolerate peripheral blood cytopenia.

Immunologic therapy targeting metastatic melanoma: allovectin-7.

In the USA, the incidence of cutaneous melanoma is increasing rapidly. It has been shown to be responsive to immune-stimulating drugs. Allovectin-7 allows the immune system to recognize metastatic melanoma lesions as foreign by incorporating a MHC class I complex into the tumor through direct injection. Once transfected, tumor biopsies have shown an increased presence of cytotoxic T lymphocytes in the tumor beds themselves. Phase I and II trials have shown local and systemic response to these tumors, with an excellent safety profile. Currently, a Phase III trial has completed enrollment and is set to determine the safety and efficacy of treatment in comparison with standard chemotherapy.