49 research outputs found

    Hydroxy-propil-β-cyclodextrin inclusion complexes of two biphenylnicotinamide derivatives: Formulation and anti-proliferative activity evaluation in pancreatic cancer cell models

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    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-β-CD is able to form stable host–guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M−1 and 369.2 M−1, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45% w/v of HP-β-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy

    Measurement of the angular correlation between the two gamma rays emitted in the radioactive decays of a 60^{60}Co source with two NaI(Tl) scintillator

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    We implemented a didactic experiment to study the angular correlation between the two gamma rays emitted in typical 60^{60}Co radioactive decays. We used two NaI(Tl) scintillators, already available in our laboratory, and a low-activity 60^{60}Co source. The detectors were mounted on two rails, with the source at their center. The first rail was fixed, while the second could be rotated around the source. We performed several measurements by changing the angle between the two scintillators in the range from 90∘90^\circ to 180∘180^\circ. Dedicated background runs were also performed, removing the source from the experimental setup. We found that the signal rate increases with the angular separation between the two scintillators, with small discrepancies from the theoretical expectations.Comment: 15 pages, 12 figure

    Microfluidic pervaporation of ethanol from radiopharmaceutical formulations

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    A pervaporation process was implemented into microfluidic chips to purify radiopharmaceuticals for Positron Emission Tomography in continuos-flow. The chip consists of a serpentine microreactor interfaced to a polydimethylsiloxane (PDMS)10 μm thick membrane. Thanks to different volatility of the components present in the radiopharmaceutical matrix, ethanol (EtOH)is readily removed under gentle heating and nitrogen flow conditions. Three classes of chips with different membrane surface areas (S)and internal volumes (V)have been produced and quantified their pervaporative efficiency at different residence times (Rt)and temperatures. Higher S/V chips (̴ 70 mm−1)apperared the most efficient at a very low residence time (Rt ̴ 10 s)allowing reduction of 67% at 80 °C. Chips of intermediate S/V ratios (̴ 30 mm−1)decreased the EtOH amount up to ̴ 90% at longer residence time (Rt ≥ 26 s). The halving of EtOH concentration in a solution of a radiotracer was obtained at 50 °C with Rt of 25 s. After the pervaporation treatment, the EtOH content in the final radiopharmaceutical formulation was demonstrated to be reduced below 10% v/v as required by the European Pharmacopea current edition

    Increased incarceration rates drive growing tuberculosis burden in prisons and jeopardize overall tuberculosis control in Paraguay

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    Incarcerated populations are at high-risk to develop tuberculosis (TB), however their impact on the population-level tuberculosis epidemic has been scarcely studied. We aimed to describe the burden and trends of TB among incarcerated populations over time in Paraguay, its clinical and epidemiological differences and the population attributable fraction. This is an observational, descriptive study including all TB cases notified to the National TB control Program in Paraguay during the period 2009–2018. We also used case registries of prisoners diagnosed with tuberculosis from the Minister of Justice. The population attributable fraction of TB in the community due to incarcerated cases was estimated through Levin’s formula. The characteristics of TB cases in and outside of prison were compared as well as the characteristics of TB in prisons were modified over time. During 2009–2018, 2764 (9.7%) of the 28,534 TB reported cases in Paraguay occurred in prisons. The number of prisoners in Paraguay increased from 6258 in 2009 to 14,627 in 2018 (incarceration rate, 101 to 207 per 100,000 persons) while the number of TB cases among prisoners increased by 250% (n = 192 in 2009 versus n = 480 in 2018). The annual TB notification rate among male prisoners was 3218 and 3459 per 100,000 inmates in 2009 and 2018, respectively. The percentage of all TB cases occurring among prisoners increased from 7.1% in 2009 to 14.5% in 2018. The relative risk of TB in prisons compared to community was 70.3 (95% CI, 67.7–73.1); the overall population attributable risk was 9.5%. Among the 16 penitentiary centers in the country, two of them—Tacumbú (39.0%) and Ciudad del Este (23.3%)—represent two thirds of all TB cases in prisons. TB among inmates is predominantly concentrated in those 20–34 years old (77.3% of all), twice the percentage of cases for the same age group outside of prison. Our findings show that the TB epidemic in prisons represents one of the most important challenges for TB control in Paraguay, especially in the country’s largest cities. Appropriate TB control measures among incarcerated populations are needed and may have substantial impact on the overall TB burden in the country
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