Individual differences in the distribution of activation among the hamstring muscle heads during stiff-leg Deadlift and Nordic hamstring exercises.

The aim of this study was to compare the distribution of activation among the three heads of the hamstring between a knee flexion-oriented exercise (Nordic hamstring) and a hip extension-oriented exercise (stiff-leg Deadlift) at the group and individual level. Data were collected for 20 participants. Muscle activation of the semimembranosus (SM), semitendinosus (ST), and biceps femoris (BF) was estimated using surface electromyography (EMG) during Nordic hamstring and stiff-leg Deadlift exercises. Although Nordic hamstring exercise induced a higher normalized RMS EMG value for BF (64.5 ± 17.4%) compared to SM (48.6 ± 14.6%; P<0.001) and ST (55.9 ± 17.4%; P < 0.001), the greatest active muscle varied between individuals. Similar interindividual differences in the greatest active muscle were found for the stiff-leg Deadlift exercise. Regarding the distribution of activation, the stiff-leg Deadlift favoured the contribution of the SM compared to ST (P < 0.001, 18/20 participants) whereas the Nordic hamstring exercise favoured the contribution of the ST compared to SM (P < 0.001, 19/20 participants). Importantly, these tasks affected the contribution of the activation of BF in different ways between individuals. The distribution of activation across the three muscles was well correlated between the two exercises (r values ≥ 0.42).

Synthesis of biobased polyurethane from oleic and ricinoleic acids as the renewable resources via the AB-type self-condensation approach.

Polyurethane (PU) from methyl oleate (derived from sunflower oil) and ricinoleic acid (derived from castor oil) was synthesized using the AB-type self-polycondensation approach for the first time. In the present work, three novel AB-type monomers, namely, a mixture of 10-hydroxy-9-methoxyoctadecanoyl azide/9-hydroxy-10-methoxyoctadecanoyl azide (HMODAz), 12-hydroxy-9-cis-octadecenoyl azide (HODEAz) and methyl-N-11-hydroxy-9-cis-heptadecen carbamate (MHHDC) were synthesized from methyl oleate and ricinoleic acid using simple reaction steps. Out of these, HMODAz and HODEAz monomers were polymerized by the acyl-azido and hydroxyl AB-type self-condensation approach, while MHHDC monomer was polymerized through AB-type self-condensation via transurethane reaction. The acyl-azido and hydroxyl self-condensations were carried out at various temperatures (50, 60, 80. and 110 degrees C) in bulk with and without catalyst. A FTIR study of the polymerization, using HMODAz at 80 degrees C without catalyst, indicates in situ formation of an intermediate isocyanate group in the first 15-30 min, and further onward, the molar mass increases as observed by SEC analysis. In the case of the MHHDC monomer, a transurethane reaction was used to obtain a similar PU (which was obtained by AB-type acyl-azido and hydroxyl self-condensation of HODEAz) in the presence of titanium tetrabutoxide as a catalyst at 130 degrees C. HMODAz, HODEAz, MHHDC, and corresponding polyurethanes were characterized by FTIR, (1)H NMR, (13)C NMR, and MALDI-TOF mass spectroscopy. Differential scanning calorimetric analysis of polyurethanes derived from HMODAz, HODEAz, and MHHDC showed two different glass transition temperatures for soft segments (at lower temperature) and hard segments (at higher temperature), indicating phase-separated morphology.

Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate.

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

Anti-tumor properties of human-activated macrophages produced in large scale for clinical application.

When properly activated, macrophages can be tumoricidal. To harness the therapeutic potential of these cells, we have developed a process for ex vivo production of large numbers of IFN-gamma-activated monocyte-derived macrophages. These monocyte-derived activated killer (MAK) cells have been safely administered to cancer patients with minimal residual disease in phase I/II clinical studies. To evaluate efficacy of treatment with MAK cells, phase III clinical studies are necessary. The process of MAK cell production has been further optimized and qualified for use in large cohorts of patients. In this study, we characterized MAK cells produced in large scale by studying their phenotype and functions. MAK cells were shown to exert anti-tumor activity by killing tumor cells and inhibiting their proliferation. These activities were enhanced by activation with IFN-gamma and addition of anti-tumor antibodies. Tumor necrosis factor-alpha (TNF-alpha) was one of the mediators used by MAK cells to inhibit tumor proliferation. To facilitate logistics of clinical trials, a process for MAK cell cryopreservation has been developed. We verified in vitro that cryopreserved cells retained the activity of fresh cells and were stable during storage. The safety and efficacy of cryopreserved MAK cells (Bexidem) are currently being assessed on superficial bladder cancer patients in a phase II/III clinical trial.

Identification of a clinical-grade maturation factor for dendritic cells.

Dendritic cells (DC) are essential for the generation of primary adaptive immune responses, but their full immunostimulatory capacities are only reached upon maturation. The authors compared several clinical-grade adjuvants of bacterial origin to determine their ability to induce phenotypic and functional maturation of monocyte-derived DC (Dendritophages, Dphi; IDM, Paris, France) differentiated with granulocyte-macrophage colony-stimulating factor and interleukin-13 in single-use cell processors (VacCell; IDM, Paris, France). Monophosphoryl lipid A, Mycobacterium bovis bacillus Calmette-Guerin, and Ribomunyl (Pierre Fabre Medicament, Boulogne, France) all appeared able to provide the signal necessary to initiate Dphi maturation. However, only Ribomunyl (Pierre Fabre Medicament) (containing membrane and ribosomal fractions from four bacterial strains) allowed the authors to obtain a significant enhancement of allostimulatory abilities and cytokine production by Dphi in the absence of active cellular infection. Addition of interferon-gamma (IFN-gamma) to Ribomunyl resulted in more pronounced upregulation of CD83, major histocompatibility complex class I, and B7 molecules by Dphi. Moreover, the IFN-gamma addition modulated their cytokine secretion, allowing higher levels of bioactive interleukin-12 concomitant with lower levels of interleukin-10. In kinetic studies, Dphi contact with Ribomunyl and IFN-gamma for 6 hours was sufficient to trigger a maturation process that completed spontaneously. Thus, Ribomunyl in association with IFN-gamma represents a suitable agent for the ex vivo production of mature monocyte-derived DC that can be used as cellular vaccines to promote a potent type I immune response.