Real-life use of ropeg-interferon α2b in polycythemia vera: patient selection and clinical outcomes.

Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

Genetic diversity, structure and individual assignment of Casta Navarra cattle: a well-differentiated fighting bull population.

The Casta Navarra lineage was one of the populations used to establish the fighting bull (FB) breed, and it has also been reproductively isolated from the others FBs. A total of 1284 individuals from two generations of 16 Casta Navarra herds were sampled to analyse their diversity, their genetic structure and the ability of 28 microsatellite markers to assign individuals to closely related populations. These animals were compared with closely related phylogenetic (FB) or geographical (Pirenaica and Monchina) populations. Hardy-Weinberg equilibrium analysis showed that 82% of the loci had a significant heterozygote deficit as a consequence of the Wahlund effect. The average proportion of genetic variation explained by farm differences was 9% by Wright's FST index. A phylogenetic tree constructed with a neighbour-joining method based on Reynolds genetic distances and a Bayesian Markov chain Monte Carlo clustering approach revealed clear differences between farm groups that generally corresponded to historical information and could unambiguously differentiate Casta Navarra cattle from the other populations. The percentage of animals correctly assigned to the Casta Navarra population was 91.78% for a q threshold of >0.9. Admixture was only detected in 4.45% (q < 0.8) of the cattle. These results are relevant for the maintenance and development of diversity and conservation in the Casta Navarra population.

Comparative study of divalent metals and amines as silanol-blocking agents in reversed-phase liquid chromatography.

In this work we compare the silanol-blocking ability of different alkaline earth metal cations, including calcium, magnesium and barium, and strong amine silanol blockers, such as triethylamine and octylamine, using six basic probe solutes at pH 7 on a conventional octadecylsilane phase. Some amines are better blocking agents than the metal cations but this varies with the amine and analyte structure. Among the metals, barium is the best blocker. For certain solutes barium is as effective at blocking silanols as some of the amine blockers. It produces short retention times and good peak shapes with satisfactory peak symmetry factors. However, amines with long alkyl chains, such as octylamine, are better blocking agents than barium. Peak symmetry is still poor for some solutes even in the presence of the strongest blocking agent in the eluent.

Room temperature phosphorescence of 1-naphtalenacetamide included in beta-cyclodextrin in presence of 1,3-dibromopropane.

The spectral characteristics of the inclusion of 1-naphthalenacetamide in beta-cyclodextrin have been studied by luminescence methods. The addition of bromoalcohols or bromoalkanes produces a decrease of the fluorescence of the inclusion complex, giving rise to a new band corresponding to phosphorescence emission. The emission intensity is much higher in the presence of bromoalkanes than in the presence of bromoalcohols. The deoxygenation of the solutions is achieved by flowing nitrogen, by the addition of sodium sulphite and by a combination of both methods, which results in the most effective approach. The phosphorescence emission is produced in the turbid suspension formed in the presence of the bromoalkane. The formation of microcrystals seems necessary to obtain phosphorescence emission from the ternary system.

[Long term study on the efficacy and safety of lornoxicam in rheumatoid arthritis]. / Studio a lungo termine su efficacia e sicurezza terapeutica di lornoxicam nell'artrite reumatoide.

BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam, a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS: Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg bid and 4mg tid) administered for six to twelve months. Patients of both sexes were enrolled, with classical or definite rheumatoid arthritis according to the A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years. Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term treatment. Clinical improvement was limited, but progression of the disease was controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented a worth-while therapeutic action and a good tolerability in rheumatoid arthritis long term treatment.

[4 cases of Horton's temporal arteritis. Hypothesis on the possible correlations with rheumatic polymyalgia]. / Quattro casi di arterite temporale di Horton. Ipotesi sulle possibili correlazioni con la polimialgia reumatica.

Giant cell arteritis (GCA) or temporal arteritis is an entity of unknown aetiology and uncertain autonomy for the close relationship with polymyalgia rheumatica (PMR). This work describes four patients with GCA alone. All patients had clinical and laboratoristic evidence of the disease and were treated with steroids. The distribution of HLA antigens showed an increased occurrence of DR4 and B8 antigens. Unfortunately, the small number of patients and the short period of observation don't allow to prove the exact nature of the link between GCA and PMR.

Development of an ionic liquid-based dispersive liquid-liquid microextraction method for the determination of nifurtimox and benznidazole in human plasma.

Dispersive ionic liquid-liquid microextraction combined with liquid chromatography and UV detection was used for the determination of two antichagasic drugs in human plasma: nifurtimox and benznidazole. The effects of experimental parameters on extraction efficiency-the type and volume of ionic liquid and disperser solvent, pH, nature and concentration of salt, and the time for centrifugation and extraction-were investigated and optimized. Matrix effects were detected and thus the standard addition method was used for quantification. This microextraction procedure yielded significant improvements over those previously reported in the literature and has several advantages, including high inter-day reproducibility (relative standard deviation=1.02% and 3.66% for nifurtimox and benznidazole, respectively), extremely low detection limits (15.7 ng mL(-1) and 26.5 ng mL(-1) for nifurtimox and benznidazole, respectively), and minimal amounts of sample and extraction solvent required. Recoveries were high (98.0% and 79.8% for nifurtimox and benznidazole, respectively). The proposed methodology offers the advantage of highly satisfactory performance in addition to being inexpensive, simple, and fast in the extraction and preconcentration of these antichagasic drugs from human-plasma samples, with these characteristics being consistent with the practicability requirements in current clinical research or within the context of therapeutic monitoring.

Comparison between phase-transfer and cloud-point methodologies for the micellar extraction of biogenic amines.

We compared the recently developed surfactant-based extraction with sodium bis-[2-ethylhexyl]-sulphosuccinate (AOT) in heptane (the phase-transfer method) and the well established methodology with poly(oxyethylene)-7,5-(p-tert-octylphenyl) ether (Triton X-114; the cloud-point technique) to extract and preconcentrate biogenic amines. Both procedures were optimized and applied to the extraction of biogenic amines from a beer sample. In order to improve the degree and monitoring of the extraction otherwise achieved with underivatized amines, the fluorescent reagent dansyl chloride was used. Since the different procedures described in the literature are not in agreement, we optimized the derivatization reaction. Accordingly a systematic investigation of the experimental variables, one by one, yielded the following optimum conditions: dansyl chloride, 5mg/mL; 27 degrees C; reaction time, 25min; pH, 10.35 at ionic strength, 0.7mol/L. Both surfactant-based extraction procedures are simple and sensitive, but the use of AOT instead of Triton X-114 offers certain advantages. Detection limits of between 0.03 and 0.8pmol injected were obtained when AOT was used, whose range is similar to or better than the other published techniques; while the corresponding values for Triton X-114 were between 0.2 and 1.2pmol injected. The phase-transfer extraction is faster than the cloud-point method, and no heating is required. For both approaches, the recovery was very high for all the amines studied and the reproducibility quite good for almost all. Upon comparison of calibration curves in pure water with those in the presence of samples, matrix effects were detected.

Comparative study of hydrocarbon, fluorocarbon, and aromatic bonded RP-HPLC stationary phases by linear solvation energy relationships.

The retention properties of eight alkyl, aromatic, and fluorinated reversed-phase high-performance liquid chromatography bonded phases were characterized through the use of linear solvation energy relationships (LSERs). The stationary phases were investigated in a series of methanol/water mobile phases. LSER results show that solute molecular size and hydrogen bond acceptor basicity under all conditions are the two dominant retention controlling factors and that these two factors are linearly correlated when either different stationary phases at a fixed mobile-phase composition or different mobile-phase compositions at a fixed stationary phase are considered. The large variation in the dependence of retention on solute molecular volume as only the stationary phase is changed indicates that the dispersive interactions between nonpolar solutes and the stationary phase are quite significant relative to the energy of the mobile-phase cavity formation process. PCA results indicate that one PCA factor is required to explain the data when stationary phases of the same chemical nature (alkyl, aromatic, and fluoroalkyl phases) are individually considered. However, three PCA factors are not quite sufficient to explain the whole data set for the three classes of stationary phases. Despite this, the average standard deviation obtained by the use of these principal component factors are significantly smaller than the average standard deviation obtained by the LSER approach. In addition, selectivities predicted through the LSER equation are not in complete agreement with experimental results. These results show that the LSER model does not properly account for all molecular interactions involved in RP-HPLC. The failure could reside in the V2 solute parameter used to account for both dispersive and cohesive interactions since "shape selectivity" predictions for a pair of structural isomers are very bad.