Aloinjerto de matriz ósea descalcificada versus injerto autólogo en la reparación de defectos óseos segmentarios masivos. : Estudio experimental

Se compara la capacidad regenerativa del aloinjerto de matriz ósea descalcificada con el tradicional injerto óseo autólogo en el tratamiento de defectos osteoperiósticos de 4-5 cm, de longitud provocados experimentalment e a nivel diafisario en fémur ovino. Para este experimento, se emplearon 18 corderos de raza churra esquelé- ticament e maduros. En 8 animales, la reconstrucción del defecto diafisario se intentó mediant e el aport e aloinjerto fragmentado de matriz óse a descalcificada. En otros 6 animales, el defecto se rellenó con injerto corticoesponjoso autólogo, también fragmentado. La estabilización ósea se realizó por medio de un fijador externo. Tras efectuar estudio s radiológicos e histológicos, los resultados fueron comparado s con un grupo control de 4 animales con el mismo defecto óseo femoral, en los que no se efectuó ningún tipo de reconstrucción ósea. El injerto autólogo se mostró más eficaz que el aloinjerto de matriz ósea descalcificada para la reparación de defectos óseos segmentarios masivos. Sólo en 1 de los animale s tratados con aloinjertos de matriz ósea se observó una actividad osteogénica que condujo a la reparación y consolidación del defecto. Por el contrario, no se observó ningún fracaso en la incorporación y consolidación de los injertos autólogos en los animales que completaron los 4 mese s de estudio.The regenerative capacity of decalcified allogenic matrix was compared with that of autologous bone graft for treatment of osteoperiosteal defects, 4-5 cm in length, experimentally induced in the sheep femoral diaphysis. Eighteen skeletally matur e shee p wer e use d in this investigation. In 8 animals, the reconstructio n of the diaphyseal defect wa s performed using small fragments of decalcified allogeni c bone matrix. In othe r 6 animals, the defect wa s refilled with corticoespongious autologous bone graft in chips. Bone stabilization was achieved by means of an external fixator. After radiologic and histologic assessments, the results wer e compared with a control group including 4 animals with the same diaphyseal defect but without any attempt of reconstruction. Autologous bone graft was found to be more efficient than decalcified allogenic bone matrix for treatment of large segmental bone defects. An osteogeni c activity leading to the complete repair and consolidation of the defect wa s only detected in 1 of the animals treated with allogenic bone matrix. On the contrary, no failures in the incorporation and consolidation of grafts wer e observed in thos e animals treated with autologous bone chips

Degeneracija aksona i esteraza povezana s neuropatskim djelovanjem organofosfornih spojeva - pregled

This brief review summarises recent observations which suggest a possible mechanism for organophosphateinduced delayed neuropathy (OPIDN). Neuropathy target esterase (NTE) has been shown to deacylate endoplasmic reticulum (ER) membrane phosphatidylcholine (PtdCho). Raised levels of PtdCho are present in the brains of swiss cheese/NTE mutant Drosophila together with abnormal membrane structures, axonal and dendritic degeneration and neural cell loss. Similar vacuolated pathology is found in the brains of mice with brain-specific deletion of the NTE gene and, in old age, these mice show clinical and histopathological features of neuropathy resembling those in wild-type mice chronically dosed with tri-ortho-cresylphosphate. It is suggested that OPIDN results from the loss of NTE’s phospholipase activity which in turn causes ER malfunction and perturbation of axonal transport and glial-axonal interactions.Ovim se kratkim pregledom razmatraju nedavna opažanja koja upućuju na mogući mehanizam odgođene neuropatije uzrokovane organofosfatima (engl. organophosphate-induced delayed neuropathy, krat. OPIDN). Za esterazu povezanu s neuropatskim djelovanjem organofosfornih spojeva (engl. neuropathy target esterase, krat. NTE) dokazano je da deacilira fosfatidilkolin (PtdCho) membrane endoplazmatskog retikuluma (ER). Povišene razine PtdCho prisutne su u mozgu swiss cheese/NTE mutanta mušice Drosophila uz abnormalne membranske strukture, degeneraciju aksona i dendrita te gubitak neurona. Slična je vakuolarna patologija zamijećena u mozgu miševa u kojih je obrisan NTE gen u mozgu te koji u starijoj dobi pokazuju kliničke i histopatološke znakove neuropatije koja je slična onoj u običnih miševa kronično tretiranih tri-ortho-krezilfosfatom. Odgođena neuropatija uzrokovana organofosfatima mogla bi biti posljedicom prestanka djelovanja fosfolipaze NTE, što potom uzrokuje zatajenje endoplazmatskog retikuluma i smetnje u prijenosu signala putem aksona te interakcije između glija i aksona

Complement activation in the plasma and placentas of women with different subsets of antiphospholipid syndrome

Problem: As antiphospholipid antibody\u2010positive women with adverse pregnancy outcomes have higher plasma complement activation product levels, and the placentas of women with antiphospholipid syndrome (APS) exhibit C4d complement component deposition, complement activation involvement has been hypothesized in APS pregnancy complications. Method of study: Plasma levels of C5a and C5b\u20109 complement components of 43 APS non\u2010pregnant patients and 17 pregnant APS women were measured using enzyme\u2010 linked immunosorbent assay. The results were compared with those of 16 healthy non\u2010pregnant women and eight healthy pregnant women, respectively. Placenta samples of five APS patients at high risk of pregnancy complications and of five healthy controls were subjected to immunoblotting analysis with specific antibodies to C5b\u20109 and CD46, CD55, CD59 complement regulators. Results: The mean plasma C5a and C5b\u20109 levels were significantly higher in the nonpregnant APS patients with previous thrombosis \ub1 pregnancy morbidity (P = .0001 and P = .0034, respectively) and in the pregnant APS women with adverse outcomes (P = .0093 for both). Similarly, C5b\u20109 amounts were significantly higher in the adverse pregnancy outcome placenta (P = .0115) than in those associated to a favorable outcome. The mean CD46, CD55 and CD59 amounts were, instead, lower, although not always significantly, in the placentas of all the high\u2010risk APS women with respect to the control placentas. Conclusion: Data analysis demonstrated that there was significant complement activation in the more severe subset of APS patients and in only the adverse pregnancy outcome APS women. Further studies will clarify whether the lower CD46, CD55, and CD59 expressions in the APS placentas are limited to only high\u2010risk APS patients

Thermal fission rate around super-normal phase transition

Using Langer's $Im F$ method, we discuss the temperature dependence of nuclear fission width in the presence of dissipative environments. We introduce a low cut-off frequency to the spectral density of the environmental oscillators in order to mimic the pairing gap. It is shown that the decay width rapidly decreases at the critical temperature, where the phase transition from super to normal fluids takes place. Relation to the recently observed threshold for the dissipative fission is discussed.Comment: 12 pages, Latex, Submitted to Physical Review C for publication, 3 Postscript figures are available by request from [email protected]

A search for optical and near-infrared counterparts of the compact binary merger GW190814

We report on our observing campaign of the compact binary merger GW190814, detected by the Advanced LIGO and Advanced Virgo detectors on August 14th, 2019. This signal has the best localisation of any observed gravitational wave (GW) source, with a 90% probability area of 18.5 deg$^2$, and an estimated distance of ~ 240 Mpc. We obtained wide-field observations with the Deca-Degree Optical Transient Imager (DDOTI) covering 88% of the probability area down to a limiting magnitude of $w$ = 19.9 AB. Nearby galaxies within the high probability region were targeted with the Lowell Discovery Telescope (LDT), whereas promising candidate counterparts were characterized through multi-colour photometry with the Reionization and Transients InfraRed (RATIR) and spectroscopy with the Gran Telescopio de Canarias (GTC). We use our optical and near-infrared limits in conjunction with the upper limits obtained by the community to constrain the possible electromagnetic counterparts associated with the merger. A gamma-ray burst seen along its jet's axis is disfavoured by the multi-wavelength dataset, whereas the presence of a burst seen at larger viewing angles is not well constrained. Although our observations are not sensitive to a kilonova similar to AT2017gfo, we can rule out high-mass (> 0.1 M$_{\odot}$) fast-moving (mean velocity >= 0.3c) wind ejecta for a possible kilonova associated with this merger.Comment: 17 pages, 11 figures, 5 tables; updated acknowledgement section. Accepted for publication in MNRAS (10 September 2020

Recent advances in Pichia pastoris as host for heterologous expression system for lipases : a review

The production of heterologous lipases is one of the most promising strategies to increase the productivity of the bioprocesses and to reduce costs, with the final objective that more industrial lipase applications could be implemented. In this chapter, an overview of the new success in synthetic biology, with traditional molecular genetic techniques and bioprocess engineering in the last 5 years in the cell factory Pichia pastoris, the most promising host system for heterologous lipase production, is presented. The goals get on heterologous Candida antarctica, Rhizopus oryzae, and Candida rugosa lipases, three of the most common lipases used in biocatalysis, are showed. Finally, new cell factories producing heterologous lipases are presented

Primary Effusion Lymphoma Cell Death Induced by Bortezomib and AG 490 Activates Dendritic Cells through CD91

To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients

Identification of HIV-1 Epitopes that Induce the Synthesis of a R5 HIV-1 Suppression Factor by Human CD4+ T Cells Isolated from HIV-1 Immunized Hu-PBL SCID Mice

We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4+ T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vitro and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4+ but not CD8+ T cells. Human CD4+ T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4+ T cells. Aliquots of these re-stimulated CD4+ T cells were then co-cultured with similar APC's that were previously pulsed with 10 μg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-Υ. The data presented herein show that the HIV-1 primed CD4+ T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4+ T cells. Simultaneous production of human interferon (IFN)-Υ was observed in some cases. These results indicate that human CD4+ T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4+ T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1