New Variant of the Treatment of Acromion-Clavicular Dislocation with TightRope®System in a Mini - Open Approach: A Preliminary Clinical Study

Background: Many different surgical techniques have been described to stabilize the acromion-clavicular (AC) dislocations. So far many of these procedures are performed only in arthroscopy. Objectives: In this study, we describe a new technique that utilizes the tightrope with a mini-invasive open approach for the acute stabilization of the acromion-clavicular joint (ACJ) dislocation. Patients and Methods: We set an prospective study aimed to verify the efficacy of this new surgical technique. We treated 28 patients with acute ACJ dislocation with ACJ TightRope ® System with dual mini access. We retrospectively reviewed the data of 34 patients treated with arthroscopic technique. They were considered as the control group. Results: At 6 month’s follow-up, all the 28 patients showed a stable joint during clinical examination and obtained an average Constant score of 98.62/100, with a complete recovery of ROM and strength in abduction. The mean operation time was of 33.7 minutes. The mean recovery duration was 102.8 days. No significant difference was found between the experimental and control groups (P > 0.05). Conclusions: Results of this trial suggest the effectiveness of this new mini-invasive surgical technique in producing clinical and functional recovery in patients with ACJ dislocations

Hydroxyapatite nanocrystals as a smart, pH sensitive, delivery system for kiteplatin

Hydroxyapatite (HA) nanocrystals are important inorganic constituents of biological hard tissues in vertebrates and have been proposed as a bone substitute or a coating material for prostheses in biomedicine. Hydroxyapatite is also amenable for its capacity to bind to a great variety of biomolecules and therapeutic agents. As drug carriers, apatite nanoparticles also have the advantage of pH dependent solubility and low toxicity. Thus HA nanoparticles are negligibly soluble at physiological pH but their dissolution is accelerated at lower pH such as that typically found in the vicinity of tumors. In the present study we have investigated the adsorption on and the release from biomimetic HA nanoparticles of two platinum derivatives of cis-1,4-diaminocyclohexane ([PtX2(cis-1,4-DACH)], X2 = Cl2 (1) and 1,1-cyclobutanedicarboxylate (CBDCA, 2)). The first of the two compounds proved to be active against colon cancer cells also resistant to oxaliplatin. The release has been investigated as a function of pH to mimic the different physiological environments of healthy tissues and tumors, and the in vitro cytotoxicity of the releasates from the HA matrices has been assessed against various human cancer cell lines. The results fully confirmed the potential of 1-loaded HA nanoparticles as bone-specific drug delivery devices

Phytoplankton blooms during austral summer in the Ross Sea, Antarctica: Driving factors and trophic implications

During the austral summer of 2014, an oceanographic cruise was conducted in the Ross Sea in the framework of the RoME (Ross Sea Mesoscale Experiment) Project. Forty-three hydrological stations were sampled within three different areas: the northern Ross Sea (RoME 1), Terra Nova Bay (RoME 2), and the southern Ross Sea (RoME 3). The ecological and photophysiological characteristics of the phytoplankton were investigated (i.e., size structure, functional groups, PSII maximum quantum efficiency, photoprotective pigments), as related to hydrographic and chemical features. The aim was to identify the mechanisms that modulate phytoplankton blooms, and consequently, the fate of organic materials produced by the blooms. The observed biomass standing stocks were very high (e.g., integrated chlorophyll-a up to 371 mg m-2 in the top 100 m). Large differences in phytoplankton community composition, relative contribution of functional groups and photosynthetic parameters were observed among the three subsystems. The diatoms (in different physiological status) were the dominant taxa in RoME 1 and RoME 3; in RoME 1, a post-bloom phase was identified, whereas in RoME 3, an active phytoplankton bloom occurred. In RoME 2, diatoms co-occurred with Phaeocystis antarctica, but were vertically segregated by the upper mixed layer, with senescent diatoms dominating in the upper layer, and P. antarctica blooming in the deeper layer. The dominance of the phytoplankton micro-fraction over the whole area and the high Chl-a suggested the prevalence of non-grazed large cells, independent of the distribution of the two functional groups. These data emphasise the occurrence of significant temporal changes in the phytoplankton biomass in the Ross Sea during austral summer. The mechanisms that drive such changes and the fate of the carbon production are probably related to the variations in the limiting factors induced by the concurrent hydrological modifications to the Ross Sea, and they remain to be fully clarified. The comparison of conditions observed during summer 2014 and those reported for previous years reveal considerably different ecological assets that might be the result of current climate change. This suggests that further changes can be expected in the future, even at larger oceanic scales

Synthesis, characterization, and cytotoxicity of dinuclear platinum-bisphosphonate complexes to be used as prodrugs in the local treatment of bone tumours

For over 30 years cisplatin has been one of the most active antitumour agents in clinical use, nevertheless research for overcoming cisplatin toxicity and resistance or for improving its efficacy has never ceased. In this context we have recently proposed dinuclear Pt complexes with bridging geminal bisphosphonates as novel Pt-prodrugs with potential activity at the bone surface after embedment in inorganic matrices and implantation at the tumour site. In the present paper we report the synthesis and full characterization of four new platinum complexes having a dinuclear structure with a bisphosphonate (2-ammonium-1-hydroxyethane-1,1-diyl-bisphosphonate or 3-ammonium-1-hydroxypropane-1,1-diyl-bisphosphonate, AHBP-H and PAM-H, respectively) acting as a bridging ligand between two platinum moieties (cis-[Pt(NH(3))(2)](2+), directly related to cisplatin, and [Pt(cis-1,4-DACH)](2+), known to be able to overcome the cisplatin resistance). Moreover, as a preliminary investigation, the in vitro cytotoxicity of the new complexes has been evaluated on a panel of 13 human tumour cell lines including cisplatin-and multidrug-resistant sublines

Multi-Acting Mitochondria-Targeted Platinum(IV) Prodrugs of Kiteplatin with α-Lipoic Acid in the Axial Positions

Platinum(II) drugs are activated intracellularly by aquation of the leaving groups and then bind to DNA, forming DNA adducts capable to activate various signal-transduction pathways. Mostly explored in recent years are Pt(IV) complexes which allow the presence of two additional ligands in the axial positions suitable for the attachment of other cancer-targeting ligands. Here we have extended this strategy by coordinating in the axial positions of kiteplatin ([PtCl₂(cis-1,4-DACH)], DACH = Diaminocyclohexane) and its CBDCA (1,1-cyclobutanedicarboxylate) analogue the antioxidant α-Lipoic acid (ALA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK). The new compounds (cis,trans,cis-[Pt(CBDCA)(ALA)₂(cis-1,4-DACH)], 2, and cis,trans,cis-[PtCl₂(ALA)₂(cis-1,4-DACH)], 3), after intracellular reduction, release the precursor Pt(II) species and two molecules of ALA. The Pt residue is able to target DNA, while ALA could act on mitochondria as activator of the pyruvate dehydrogenase complex, thus suppressing anaerobic glycolysis. Compounds 2 and 3 were tested in vitro on a panel of five human cancer cell lines and compared to cisplatin, oxaliplatin, and kiteplatin. They proved to be much more effective than the reference compounds, with complex 3 most effective in 3D spheroid tumor cultures. Notably, treatment of human A431 carcinoma cells with 2 and 3 did not determine increase of cellular ROS (usually correlated to inhibition of mitochondrial PDK) and did not induce a significant depolarization of the mitochondrial membrane or alteration of other morphological mitochondrial parameters

Dual-acting antitumor Pt(iv) prodrugs of kiteplatin with dichloroacetate axial ligands

With the aim to obtain dual acting drugs able to target both nuclear DNA and mitochondria, Pt(IV) kiteplatin derivatives having dichloroacetate (DCA) ligands in axial positions have been synthesized. The rather fast hydrolysis (t1/2 of ca. 1 h) and reduction (by ascorbic acid) of these Pt(IV) derivatives did not impede a potent pharmacological effect on tumor cells. Moreover, similarly to kiteplatin, also the Pt(IV)-DCA compounds proved to be capable of overcoming oxaliplatin-resistance, which is particularly important in view of the fact that metastatic colorectal cancer is the third most common cancer in males and the second in females. The possible role of DCA released by the Pt(IV) compounds in eliciting the antiproliferative activity has also been investigated. Pt(IV)-DCA compounds determine a substantial increase of ROS production, blockage of oxidative phosphorylation, hypopolarization of the mitochondrial membrane, and caspase-3/7 mediated apoptotic cell death

Novel Kiteplatin Pyrophosphate Derivatives with Improved Efficacy

Two new Pt(II) derivatives of kiteplatin ([PtCl2(cis-1,4-DACH)]) with pyrophosphate as carrier ligand, one mononuclear (1) and one dinuclear (2), were synthesized with the aim of potentiating the efficacy of kiteplatin. Complex 1 resulted to be remarkably stable at physiological pH, but it undergoes a fast hydrolysis reaction at acidic pH releasing free pyrophosphate and (aquated) kiteplatin. The dinuclear compound 2 resulted to be less stable than 1 at both neutral and acidic pH forming 1 and (aquated) kiteplatin as first step. Both compounds (1 and 2) do not react as such with 5'-GMP, whereas their hydrolysis products readily form adducts with the nucleotide. The in vitro cytotoxicity assays against a panel of six human cancer cell lines showed that complex 2 affects cancer cell viability even at nanomolar concentrations. The cytotoxic activity of 2 is greater (up to 2 orders of magnitude) than that of cisplatin, oxaliplatin, and kiteplatin, whereas the mononuclear complex 1 has shown a cytotoxic activity comparable to that of oxaliplatin and kiteplatin, but higher than cisplatin. The latter result is not surprising, since the presence of two negative charges reduces the uptake of 1 into the tumor cells as compared to the neutral compound 2. The remarkable activity of 2 against the pancreatic cell line BxPC3 (average IC50 = 0.07 μM) deserves further investigation