Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition. Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.     

Radiological Evaluation of Acetabular Erosion After Antibiotic-Impregnated Polymethylmethacrylate Spacer (Spacer-G)

Different types of hip spacers have been described (hand-made, custom-molded or prefabricated) for treatment of a chronic hip infection. A potential disadvantage of monoblock prefabricated spacer is that it may cause acetabular bone loss. This study assesses the radiological acetabular erosion using an antibiotic-impregnated pre-fabricated polymethylmethacrylate Spacer-G. We retrospectively reviewed the radiographs of thirty five patients who were managed with Spacer-G to treat chronic hip infection. No acetabular erosion were observed in thirty two patients with a mean time from the first to second stage and from the first to the last radiograph of 5.09 and 3.77 months respectively. In three patients the time between the radiographs was more than one year and the second stage was not performed; two developed a protrusion acetabuli whereas the other one a destruction of the acetabular roof. Using a Spacer-G in chronic hip infection treatment for less than one year is not associated with radiological acetabular erosion if the patient is maintained at partial weight bearing.     

Ethanol consumption enhances periodontal inflammatory markers in rats

ObjectiveThe aim of this study was to assess the short term effect of ethanol administration on periodontal disease in rats.DesignRats received either ethanol 2 g/kg or water by gastric gavage twice a day. On the fifth day ligatures were tied around the molars of half of the rats to induce periodontitis. After 7 days gingival tissue was removed and assayed for inflammatory markers. Finally, hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques.ResultsThe experimental periodontitis increased significantly the mRNA expression (p < 0.001) and activity (p < 0.001) of inducible nitric oxide synthase (iNOS) in the gingival tissue, whilst short time ethanol administration increased iNOS activity (p < 0.05) and produced an additive effect on iNOS mRNA expression augmented by periodontitis (p < 0.01). The short time ethanol administration also potentiated the periodontitis stimulatory effect on the mRNA expression of interleukin (IL)-1β (p < 0.01 and p < 0.001, in semi-quantitative and real time PCR, respectively) and on the height of periodontal ligament (p < 0.05). However, the ligature-induced periodontitis, but not ethanol administration, increased the prostaglandin E₂ content (p < 0.05) and, diminished the alveolar bone volume (p < 0.05), as compared to sham rats.ConclusionThe present results suggest that ethanol consumption could represent a risk indicator for periodontal disease since augments the expression of inflammatory markers, in healthy rats, and increases them, at short term, during the illness. However, scale longitudinal investigation and more case–control studies are needed to confirm this statement.     

Delayed and asynchronous ganglionic maturation during cephalopod neurogenesis as evidenced by Sof‐elav1 expression in embryos of Sepia officinalis (Mollusca,Cephalopoda)

Among the Lophotrochozoa, centralization of the nervous system reaches an exceptional level of complexity in cephalopods, where the typical molluscan ganglia become highly developed and fuse into hierarchized lobes. It is known that ganglionic primordia initially emerge early and simultaneously during cephalopod embryogenesis but no data exist on the process of neuron differentiation in this group. We searched for members of the elav/hu family in the cuttlefish Sepia officinalis, since they are one of the first genetic markers of postmitotic neural cells. Two paralogs were identified and the expression of the most neural‐specific gene, Sof‐elav1, was characterized during embryogenesis. Sof‐elav1 is expressed in all ganglia at one time of development, which provides the first genetic map of neurogenesis in a cephalopod. Our results unexpectedly revealed that Sof‐elav1 expression is not similar and not coordinated in all the prospective ganglia. Both palliovisceral ganglia show extensive Sof‐elav1 expression soon after emergence, showing that most of their cells differentiate into neurons at an early stage. On the contrary, other ganglia, and especially both cerebral ganglia that contribute to the main parts of the brain learning centers, show a late extensive Sof‐elav1 expression. These delayed expressions in ganglia suggest that most ganglionic cells retain their proliferative capacities and postpone differentiation. In other molluscs, where a larval nervous system predates the development of the definitive adult nervous system, cerebral ganglia are among the first to mature. Thus, such a difference may constitute a cue in understanding the peculiar brain evolution in cephalopods. J. Comp. Neurol. 521:1482–1496, 2013. © 2012 Wiley Periodicals, Inc.     

Characteristics of differentiated CD8+ and CD4+ T cells present in the human brain

Immune surveillance of the central nervous system (CNS) by T cells is important to keep CNS-trophic viruses in a latent state, yet our knowledge of the characteristics of CNS-populating T cells is incomplete. We performed a comprehensive, multi-color flow-cytometric analysis of isolated T cells from paired corpus callosum (CC) and peripheral blood (PB) samples of 20 brain donors. Compared to PB, CC T cells, which were mostly located in the perivascular space and sporadically in the parenchyma, were enriched for cells expressing CD8. Both CD4⁺ and CD8⁺ T cells in the CC had a late-differentiated phenotype, as indicated by lack of expression of CD27 and CD28. The CC contained high numbers of T cells expressing chemokine receptor CX3CR1 and CXCR3 that allow for homing to inflamed endothelium and tissue, but hardly cells expressing the lymph node-homing receptor CCR7. Despite the late-differentiated phenotype, CC T cells had high expression of the IL-7 receptor α-chain CD127 and did not contain the neurotoxic cytolytic enzymes perforin, granzyme A, and granzyme B. We postulate that CNS T cells make up a population of tissue-adapted differentiated cells, which use CX3CR1 and CXCR3 to home into the perivascular space, use IL-7 for maintenance, and lack immediate cytolytic activity, thereby preventing immunopathology in response to low or non-specific stimuli. The presence of these cells in this tightly regulated environment likely enables a fast response to local threats. Our results will enable future detailed exploration of T-cell subsets in the brain involved in neurological diseases.     

Expression of the E-cadherin-catenins complex in sentinel node is related to tumor morphology but not to spread to nonsentinel nodes

The sentinel node (SN) technique has gained a key role in breast cancer surgery, allowing for an accurate staging of the axillary status with a minimally invasive resection. In this study, we explored the implication of three proteins (E-cadherin, a- and b-catenins) that form the cadherin-catenin complex, a receptorial structure strictly involved in tumoral vascular invasion and embolization in this biologic event. We studied the immunohistochemical expression of the complex in patients with metastatic SN, matching the group with involved nonsentinel lymph nodes (NSNs) with that having free axillary NSNs. The simultaneous staining of the SN metastases for the three proteins has been considered an indicator of preserved function. Our data confirmed the lack of cadherin-catenin complex in tumors with lobular morphology even in SN metastasis, but statistical evaluation could not prove a significant relation between complex integrity and NSN involvement. Moreover, considering traditional histopathologic parameters, only vascular peritumoral embolization was related to an increased risk of metastatic spread to axillary NSNs.     

On the Production of Chitosan-Coated Polycaprolactone Nanoparticles in a Confined Impinging Jet Reactor

This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL^?1) and of chitosan (in the range 1.5-5 mg mL^?1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min^?1 is required in the considered reactor to minimize the particle size.     

Association of Polypharmacy With 1-Year Trajectories of Cognitive and Physical Function in Nursing Home Residents: Results From a Multicenter European Study

Objectives

To test the association between polypharmacy and 1-year change in physical and cognitive function among nursing home (NH) residents.

Could COVID-19 have an impact on male fertility?

The pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to several hypotheses of functional alteration of different organs. The direct influence of this virus on the male urogenital organs is still to be evaluated. However some hypotheses can already be made, especially in the andrological field, for the biological similarity of the SARS-CoV and SARS-CoV2. As well as SARS-CoV, SARS CoV-2 uses the ‘Angiotensin Converting Enzyme-2’ (ACE2) as a receptor to enter human cells. It was found that ACE2, Angiotensin (1-7) and its MAS receptors are present, over in the lung, also in the testicles, in particular in Leydig and Sertoli cells. A first hypothesis is that the virus could enter the testicle and lead to alterations in testicular functionality. A second hypothesis is that the binding of the virus to the ACE2 receptor, could cause an excess of ACE2 and give rise to a typical inflammatory response. The inflammatory cells could interfere with the function of Leydig and Sertoli cells. Both hypotheses should be evaluated and confirmed, in order to possibly monitor fertility in patients COVID-19+.