Influence of multi-walled carbon nanotubes on the physico-chemical and biological responses of chitosan-based hybrid hydrogels.

Photoresponsive membranes were successfully obtained by combining chitosan (CS), poly(vinyl alcohol) (PVA) crosslinked with genipin (GEN) and filled with multi-walled carbon nanotubes (MWCNTs). It was demonstrated that adding a small quantity (0.01% w/v) of MWCNTs conferred to those nanocomposite hybrid hydrogels an outstanding photomechanical response under infrared irradiation. Moreover, it was observed that MWCNTs enhanced the crystallinity, increased the elastic modulus but did not contribute to the thermal stability of the nanocomposite hybrid hydrogels. The swelling capacity and contact angle values of these materials were modified through the addition of MWCNTs, and the offered free OH and NH2 functional groups in their current chemical structures. These functional groups - on hybrid hydrogels' surfaces - also enhanced the adhesion and proliferation of human dermal fibroblast cells, showing typical morphologies and sizes. Additionally, non-cytotoxic effects were observed for these nanocomposite hybrid hydrogels, suggesting their potential use in tissue engineering and biomedical applications. Chemical compounds studied in this article: Chitosan (PubChem CID: 71853); Polyvinyl alcohol (PubChem CID: 11199); Genipin (PubChem CID: 442424).

Connexin 30.2 is expressed in exocrine vascular endothelial and ductal epithelial cells throughout pancreatic postnatal development.

Previously we have demonstrated that the GJ protein connexin 30.2 (Cx30.2) is expressed in pancreatic beta cells and endothelial cells (ECs) of the islet. In the present study, we address whether Cx30.2 is expressed in the exocrine pancreas, including its vascular system. For this, adult mouse pancreatic sections were double labeled with specific antibodies against Cx30.2 and CD31, an endothelial cell marker, or with anti-α-actin smooth muscle, a smooth muscle cell (SMC) marker or anti-mucin-1, a marker of epithelial ductal cells, using immunofluorescence (IF) studies. Cx30.2-IF hot spots were found at junctional membranes of exocrine ECs and SMCs of blood vessels. Furthermore, Cx30.2 was localized in mucin-1 positive cells or epithelial ductal cells. Using immunohistochemistry (IHC) studies, it was found that in vessels and ducts of different diameters, Cx30.2 was also expressed in these cell types. In addition, it was found that Cx30.2 is already expressed in these cell types in pancreatic sections of 3, 14 and 21 days postpartum. Moreover, this cell specific pattern of expression was also found in the adult rat, hamster and guinea pig pancreas. Expression of Cx30.2 mRNA and protein in the pancreas of all these species was confirmed by RT-PCR and Western blot studies. Overall, our results suggest that intercellular coupling mediated by Cx30.2 intercellular channels may synchronize the functional activity of ECs and SMCs of vascular cells, as well as of epithelial ductal cells after birth.

Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model.

BACKGROUND: The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). METHOD: The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor ß cytokine (T G F-ß). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. RESULTS: The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time " τ", the maximal growth rate of tumor "r" and the maximal efficiency of tumor cytotoxic cells rate "aT" are the most sensitive model parameters. CONCLUSION: By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results.

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

Non-specific esterase-positive dendritic cells in epithelia of the frog Rana pipiens.

Langerhans cells are antigen-presenting cells located in epithelia and have a dendritic outline, a convoluted nucleus surrounded by an electron lucent cytoplasm with sparse organelles and occasionally containing the characteristic Birbeck granule; their membrane contains class II molecules of the major histocompatibility complex and a strong membrane reactivity for both ATPase and non-specific esterase. Despite increasing knowledge about mammalian Langerhans cells, only a few studies have examined the possible occurrence of Langerhans-like cells in lower vertebrates. Our group has previously demonstrated the presence of dendritic cells in different epithelial membranes co-expressing a strong membrane ATPase reactivity and class II molecules of the major histocompatibility complex in the frog Rana pipiens. Adding another criterion in the characterization of Langerhans-like cells in amphibians, we now report evidence for the expression of membrane non-specific esterase reactivity in dendritic cells located in the epidermis, nictitant membrane and cornea with topographical and light and electron microscopical characteristics identical to those previously described for dendritic cells positive for ATPase and major histocompatibility complex class II in Rana pipiens. We postulate that, taking all this data together, these dendritic intraepithelial cells constitute the amphibian counterpart of mammalian Langerhans cells.

ATPase and MHC class II molecules co-expression in Rana pipiens dendritic cells.

Mammalian Langerhans cells are antigen-presenting cells located in different epithelia. These cells have a characteristic ultrastructural pattern, present a plasmatic membrane ATPase activity and constitutively express class II molecules of the major histocompatibility complex. ATPase-positive dendritic cells that are morphologically similar to Langerhans cells have also been found in amphibian epidermis. In order to demonstrate that ATPase-positive dendritic cells of amphibian epidermis express class II molecules and are present in other stratified epithelia, histochemical and immunohistochemical as well as ultrastructural analysis were performed. ATPase-positive dendritic cells and class II-positive dendritic cells were observed in epidermis, nictitant membrane and cornea. In epidermis the number of ATPase-positive dendritic cells was 656+/-186/mm2 while class II-positive dendritic cells was 119+/-45/mm2. Some ATPase-positive dendritic cells showed co-expression of class II molecules. These results suggest the existence of dendritic cell subsets in amphibians as is clearly demonstrated in mammals.

Adenosine triphosphatase-positive Langerhans-like cells in the epidermis of the chicken (Gallus gallus).

In mammalian epidermis a population of ATPase-positive dendritic cells, identified as Langerhans cells, has been found. Such cells are bone marrow-derived and participate in the immunological functions of the skin. We demonstrate the existence of ATPase-positive dendritic cells in separated epidermal sheets of chicken skin, by means of light and electron microscopy. They have a mean distribution of 688 +/- 265 cells/mm2 and showed several features in common with Langerhans cells. Since chickens can develop contact dermatitis, the finding is taken as the first formal demonstration of the presence of Langerhans cells in this group of vertebrates.