Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates

ABSTRACT — Knee pathologies including focal cartilage injuries, osteoarthritis (OA), and ligament injuries are common. The poor regeneration and healing potential of cartilage has led to the search for other treatment modalities with improved healing capacity. Furthermore, with an increasing elderly population that desires to remain active, the burden of knee pathologies is expected to increase. Increased sports participation and the desire to return to activities faster is also demanding more effective and minimally invasive treatment options. Thus, the use of biologic agents in the treatment of knee pathologies has emerged as a potential option. Despite the increasing use of biologic agents for knee pathology, there are conflicting results on the efficacy of these products. Furthermore, strong data supporting the optimal preparation methods and composition for widely used biologic agents, such as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), largely remain absent from the literature. This review presents the literature on the most commonly employed biologic agents for the different knee pathologies

Role of poly [adp-ribose] polymerase 1 in activating the kirsten ras (Kras) gene in response to oxidative stress

In pancreatic Panc-1 cancer cells, an increase of oxidative stress enhances the level of 7,8-dihydro-8-oxoguanine (8OG) more in the KRAS promoter region containing G4 motifs than in non-G4 motif G-rich genomic regions. We found that H2O2 stimulates the recruitment to the KRAS promoter of poly [ADP-ribose] polymerase 1 (PARP-1), which efficiently binds to local G4 structures. Upon binding to G4 DNA, PARP-1 undergoes auto PARylation and thus becomes negatively charged. In our view this should favor the recruitment to the KRAS promoter of MAZ and hnRNP A1, as these two nuclear factors, because of their isoelectric points >7, are cationic in nature under physiological conditions. This is indeed supported by pulldown assays which showed that PARP-1, MAZ, and hnRNP A1 form a multiprotein complex with an oligonucleotide mimicking the KRAS G4 structure. Our data suggest that an increase of oxidative stress in Panc-1 cells activates a ROS-G4-PARP-1 axis that stimulates the transcription of KRAS. This mechanism is confirmed by the finding that when PARP-1 is silenced by siRNA or auto PARylation is inhibited by Veliparib, the expression of KRAS is downregulated. When Panc-1 cells are treated with H2O2 instead, a strong up-regulation of KRAS transcription is observed

The Plio-Quaternary uplift of the Apennine Chain: new data from the analysis of topography and river valleys in Central Italy

This study aimed at the reconstruction of magnitude and timing of uplift of a wide sector of the Central Apennines (Italy) by means of morphometric and morphostructural analyses. In the internal portion of the chain (where stratigraphic and geomorphological markers of past sea-level positions are lacking) the study was based on analysis of erosional landforms and river valleys. A large-scale topographic analysis was performed, processing 90-m and 230-m DEMs. The spatial distribution of several morphometric parameters, together with characteristic wavelengths of relief, allowed the distinction of three main regions affected by different cumulative surface uplift and tectonic/erosional fragmentation: a Peri-Tyrrhenian Belt; an Axial Belt; a Peri-Adriatic Belt. Particular attention was devoted to fluvial landforms, with analysis of longitudinal profiles and geometric pattern of the main stream-trunks and their relations with major structures. Major differences occur between the Tyrrhenian and Adriatic valley systems, the former being generally longitudinal and showing overall concave-upward longitudinal profiles, whereas the latter are generally transverse and possess less regular longitudinal profiles. Topographic features and river valleys architecture seem related to different styles and amounts of uplift in the three Belts. Within the study area, a narrower coast to coast transect (Gaeta-Vasto Transect, GVT) was investigated in detail, devoting particular attention to its axial sector, lying around the Apennines main divide (main divide area: MDA), and a possible scheme of the Quaternary surface uplift inside this transect was proposed. In the MDA, the main stages of landscape evolution and river network organization were reconstructed by analysis of paleosurfaces coupled with analysis of relic and present-day hydrographic network. This allowed recognition of a major phase of surface uplift (exceeding 1500 m in the Meta-Mainarde massif) occurred in response to thrusting during the Pliocene, whereas for the Quaternary uplift a minimum value around 400 m was estimated. Our study suggests that, during the Quaternary and in the GVT, the Peri-Tyrrhenian Belt suffered a subdued uplift operating over small wavelengths (10-15 km), while Axial and Peri- Adriatic Belts were subject to a stronger and long-wavelength (90 km) surface uplift, with maximum values (about 700 m) shifted NE of the Axial Belt and tapering to zero towards the Adriatic coast. The reconstructed pattern of uplift is coherent with the topographic properties of the three Belts and with the observed drainage features

Seminario di Linguistica e Didattica delle Lingue. Scritti in onore degli ottant’anni di Giovanni Freddi

Include, di Balboni: “La glottodidattica veneziana: una ‘scuola’?”, pp. 19-54

A novel mutation in calcium-sensing receptor gene associated to hypercalcemia and hypercalciuria.

Background: Familial Hyperparathyroidism (HPT) and Familial benign Hypocalciuric Hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. FHH has been demonstrated to be caused by inactivating mutations of calcium-sensing receptor (CaSR) gene, involved in PTH regulation as well as in renal calcium excretion.Case presentation: In two individuals, father and son, we found a novel heterozygous mutation in CaSR gene. The hypercalcemia was present only in father, which, by contrast to the classic form of FHH showed hypercalciuria (from 300 to 600 mg/24 h in different evaluations) and a Calcium/Creatinine ratio of 0.031, instead of low or normal calciuria (<0.01 typical finding in FHH). His son showed the same mutation in CaSR gene, but no clinical signs or hypercalcemia although serum ionized calcium levels were close to the upper limit of normal values (1.30 mmol/L: normal range: 1.12-1.31 mmol/L). Sequence analysis revealed a point mutation at codon 972 of CaSR gene (chromosome 3q), located within cytoplasmic domain of the CaSR, that changes Threonine with Methionine. The father was treated with Cinacalcet 90 mg/day, with a decrease of total serum calcemia from an average value of 12.2 mg/dl to 10.9 mg/dl.Conclusion: This is a case of a novel inactivating point mutation of CaSR gene that determines an atypical clinical presentation of FHH, characterized by hypercalcemia, hypercalciuria and inadequate normal PTH levels. Functional assay demonstrated that the 972 M variant influenced the maturation of the protein, in terms of the post-translational glycosylation. The impairment of the receptor activity is in keeping with the specific localization of the 972 residue in the C-terminal tail, assigned to the intracellular signalling, that on the basis of the our findings appears to be differently modulated in parathyroid gland and in kidne

Evolutive follow-up of the photocatalytic degradation of real textile effluents in TiO2 and TiO2/H2O2 systems and their toxic effects on Lactuca sativa seedlings

Textile industry wastes raise a great concern due to their strong coloration and toxicity. The objective of the present work was to characterize the degradation and mineralization of textile effluents by advanced oxidative processes using either TiO2 or TiO2/H2O2 association and to monitor the toxicity of the products formed during 6 h irradiation in relation to that of the in natura effluent. The results obtained demonstrated that the TiO2/H2O2 association was more efficient in the mineralization of textile effluents than TiO2 alone, with high mineralized ion concentrations (NH4+, NO3-, and SO4(2-)) and significant organic matter reduction rates (represented by the COD and TOC). The toxicity of the degradation products to lettuce seeds (Lactuca sativa) was not significant, since percent germination was not significantly affected and neither was root and sprout percent growth. However, while the TiO2/H2O2 association was more toxic in the first hours of irradiation and less so in the end of the 6 h irradiation, the toxicity of TiO2 increased only slightly in the end of the experiments. Comparatively, the photogenerated products of both the TiO2 and the TiO2/H2O2 association were less toxic than the in natura effluent

A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report

<p>Abstract</p> <p>Introduction</p> <p>Histopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor outcomes. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis.</p> <p>Case presentation</p> <p>A 30-year-old previously healthy Japanese woman who had fever and headache for five days presented with disorganised speech, unusual behavior and delusional thinking. Real-time polymerase chain reaction amplification of herpes simplex virus type 1 in cerebrospinal fluid was positive (38,000 copies/mL) and antivirus treatment was started. During the course of her illness, the level of her consciousness decreased in association with desaturation and tachycardia. Thrombosis of the right pulmonary artery trunk with pulmonary embolism was evident on enhanced chest computed tomography. In addition, cranial computed tomography revealed subarachnoid and intraventricular bleeding. Intravenous heparin (12,000 U/day) was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximum dose of heparin, 20,400 U/day). After the treatments, her Glasgow coma score increased and the thrombosis of the pulmonary artery trunk had disappeared.</p> <p>Conclusions</p> <p>The present case raises the question of whether anticoagulant treatment is safe in patients with herpes simplex virus encephalitis complicated by subarachnoid bleeding.</p

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy

Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 μM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents