Kinetic Studies of the Copolymerization of Ethylene with Norbornene by ansa‐Zirconocene/Methylaluminoxane Catalysts: Evidence of a Long‐Lasting “Quasi‐Living” Initial Period

Copolymers of ethylene (E) with norbornene (N) were synthesized using the catalysts rac‐Et(Ind)₂ZrCl₂/MAO ( 1 ), 90%rac/10%meso‐Et(4,7‐Me₂Ind)₂ZrCl₂/MAO ( 2 ), and rac‐H₂C(3‐t‐BuInd)₂ZrCl₂/MAO ( 3 ). Catalyst activity, molar mass (MM), and copolymer composition were studied as a function of time. The polymers showed an unusually narrow molar mass distribution (MMD) and a significant increase of their MM with time for up to one hour, suggesting a “quasi‐living” polymerization at 30 °C. The experimental data were fitted to kinetic equations and the propagation and transfer reactions were described in quantitative terms. Norbornene greatly depressed the propagation rate, along with the chain transfer rate. The more sterically hindered catalysts of the series showed lower propagation and chain transfer turnover frequency than 1 and yielded polymers with a low ( 2 ) to very low ( 3 ) norbornene content. The presence of norbornene in solution seemed to be one of the main factors responsible for the observed “quasi‐living” character of the copolymerization, probably due to coordination of norbornene to the active site. Time‐resolved kinetic studies also allowed for the calculation of the fraction of active metal centers, ranging from 56% ( 3 ) and 66–68% ( 1 ) to 94% ( 2 ) of the total zirconium present, depending on catalyst structure.

Left: molar mass (top) and polydispersity (bottom) as a function of the normalized polymer yield. The dashed line is the theoretical curve for ideal living polymerization. Catalysts 1 (□), 2 (?), and 3 (○) at N/E ratio 12.5 and catalyst 1 (?) at N/E ratio 28.4. Right: enlargement of the low yield section.     

What do brain imaging studies tell us about anxiety disorders?

In-vivo neuroimaging allows the investigation of brain circuits involved in the experience of anxiety and of receptor changes associated with anxiety disorders. This review focuses on studies by research groups who have compared brain activation maps in different forms of anxiety and on binding studies of the benzodiazepine-GABA(A) receptor. Activation studies have revealed the involvement of many brain areas depending on the condition and the paradigm. However, the orbitofrontal cortex/anterior insula and the anterior cingulate are implicated in all the studies and may represent the nodal point between somatic and cognitive symptoms of any form of anxiety. Most studies of binding at the benzodiazepine-GABA(A) receptor are not interpretable because of substantial methodological problems, however, regional and/or global reductions are the most consistent finding in panic disorder.     

Photodithazine photodynamic effect on viability of 9L/lacZ gliosarcoma cell line

Even with the advances of conventional treatment techniques, the nervous system cancer prognosis is still not favorable to the patient which makes alternative therapies needed to be studied. Photodynamic therapy (PDT) is presented as a promising therapy, which employs a photosensitive (PS) agent, light wavelength suitable for the PS agent, and molecular oxygen, producing reactive oxygen species in order to induce cell death. The aim of this study is to observe the PDT action in gliosarcoma cell using a chlorin (Photodithazine, PDZ). The experiments were done with 9L/lacZ lineage cells, grown in a DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin solution and put in a culture chamber at 37 °C with an atmosphere of 5% CO₂. The PS agent used was the PDZ to an LED light source device (Biopdi/IRRAD-LED 660) in the 660-nm region. The location of the PS agent was analyzed by fluorescence microscopy, and cell viability was analyzed by MTT assay (mitochondrial activity), exclusion by trypan blue (cell viability), and morphological examination through an optical microscope (Leica MD 2500). In the analysis of the experiments with PDZ, there was 100% cell death at different concentrations and clear morphological differences in groups with and without treatment. Furthermore, it was observed that the photodithazine has been focused on all nuclear and cytoplasmic extension; however, it cannot be said for sure whether the location is in the inside core region or on the plasma membrane. In general, the PDZ showed a promising photosensitive agent in PDT for the use of gliosarcoma.     

Trauma in Cirrhosis: An Indicator of the Pattern of Alcohol Abuse in Different Societies

While some morbidities associated with the excessive use of alcohol are related to the total amount of alcohol consumed--cirrhosis being an example--other pathologies, such as trauma and those of psycho-social origin, are mainly related to the frequency of acute alcoholic intoxication rather than to the total amount consumed. The balance between these two types of alcohol-associated morbidities can provide an indication of the relative frequency of intoxication, and thus of the pattern of alcohol abuse in a population. Since trauma is highly associated with acute alcoholic intoxication, the prevalence of bone fractures was determined in cirrhotics in nine countries. The prevalence of rib and vertebral fractures on routine chest x-rays showed a 17-fold variation in the different countries, from 2% and 6% in Spain and Italy to 30% and 34% in Canada and the USA, suggesting marked differences in the pattern of alcohol abuse to intoxication. Conversely, the prevalence of cirrhosis is twice as high in Spain and Italy than in Canada and the USA. A strong positive correlation between per capita consumption and cirrhosis mortality (r = 0.86; p less than 0.01) exists among the nine countries studied, while the correlation between per capita alcohol consumption and the prevalence of trauma is not statistically significant (r = 0.40). Supporting a strong association between trauma and alcoholic intoxication, the prevalence of trauma was found to be highly correlated: r = 0.88, p less than 0.002, with the degree of concern for the psycho-social consequences of alcohol abuse in the different countries. Data indicate that trauma can be used as an objective indicator to assess the pattern of alcohol abuse in a population.     

Pain Relief after Stereotactic Radiotherapy of Pancreatic Adenocarcinoma: An Updated Systematic Review

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I² statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q² test: p < 0.0001; I² = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q² test: p < 0.008; I² = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q² test: p < 0.0001; I² = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes.     

Antimicrobial peptides: synthesis and antibacterial activity of linear and cyclic drosocin and apidaecin 1b analogues

Drosocin and apidaecin Ib are two insect antimicrobial peptides showing a significant sequence homology and a common mechanism of action, which includes stereoselective elements but is devoid of any pore-forming activity. A substantial difference between the two peptides is the presence in the drosocin sequence of an O-glycosylated threonine residue, which is important for its antimicrobial activity. Through the synthesis of a series of differently glycosylated drosocin analogues, we have shown that the antimicrobial activity against several Gram-negative bacteria appears to be modulated by the sugar moiety (Gal vs GalNAc) and the type of glycosidic linkage (alpha-O-, beta-O-, or alpha-C-). The insertion of a glycosylated threonine residue in the apidaecin Ib sequence improves the sequence homology with drosocin but reduces the antimicrobial activity. To gain information on the possible bioactive conformation of these peptides, we synthesized an unglycosylated cyclic analogue of drosocin, containing an intrachain disulfide bond, and the head-to-tail cyclic analogues of drosocin and apidaecin, as well as their corresponding cyclic dimers. Only the large cyclic dimer of apidaecin partially retained the antimicrobial activity, suggesting that a bending of the peptide chain, in particular in the middle of the molecule, is not a structural element characteristic of the bioactive conformation of drosocin and apidaecin. Experiments aimed at testing the effect of selected drosocin and apidaecin peptides on biological membranes showed that some peptides display a moderate hemolytic activity and that a dissociation between antibacterial activity and cytotoxicity to eukaryotic cells can be achieved in differently glycosylated peptide analogues.     

ON THE REACTION OF ACETAMIDOMETHANOL WITH NATIVE AND REDUCED BOVINE PANCREATIC TRYPSIN INHIBITOR (KUNITZ INHIBITOR)

The stability of native and reduced bovine pancreatic trypsin inhibitor (Kunitz inhibitor) in anhydrous hydrogen fluoride and their reaction with acetamidomethanol, in the same solvent, have been investigated. The bovine Kunitz inhibitor appears to be stable in liquid hydrogen fluoride but the reduced molecule loses about 50% of its ability to regain inhibitory power, upon air oxidation, by exposure to this solvent. Tyrosine residues appear to be affected by acetamidomethylation of the native protein to give a modified inhibitor which is still highly active in inhibiting trypsin. The extent of correct refolding, upon reoxidation, of the reduced tyrosine modified-inhibitor is greatly diminished. Tyrosine modification can be prevented by carrying out the acetamidomethylation reaction in the presence of excess anisole. The stability constants and the standard free energies of binding of the complexes between trypsin and the native and the tyrosine modified-inhibitor have been determined.